Trial Outcomes & Findings for Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma (NCT NCT00682786)
NCT ID: NCT00682786
Last Updated: 2017-10-06
Results Overview
Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1. Historical studies demonstrate a DS rate of 45%.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
135 participants
Primary outcome timeframe
1 year after enrollment
Results posted on
2017-10-06
Participant Flow
Enrollment to the study opened on 10/07/2002 and the study closed to enrollment on 10/23/2008.
Participant milestones
| Measure |
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Overall Study
STARTED
|
98
|
37
|
|
Overall Study
COMPLETED
|
96
|
34
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
|
Overall Study
Did not receive irinotecan
|
0
|
1
|
Baseline Characteristics
Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma
Baseline characteristics by cohort
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=98 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=37 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Total
n=135 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55 years
n=5 Participants
|
59 years
n=7 Participants
|
56 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
69 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
86 participants
n=5 Participants
|
29 participants
n=7 Participants
|
115 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
10 participants
n=5 Participants
|
8 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
98 participants
n=5 Participants
|
37 participants
n=7 Participants
|
135 participants
n=5 Participants
|
|
Thymidylate Synthase Enhancer Region (TSER) genotype
*2/*2
|
26 participants
n=5 Participants
|
0 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Thymidylate Synthase Enhancer Region (TSER) genotype
*2/*3
|
71 participants
n=5 Participants
|
0 participants
n=7 Participants
|
71 participants
n=5 Participants
|
|
Thymidylate Synthase Enhancer Region (TSER) genotype
*2/*4
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Thymidylate Synthase Enhancer Region (TSER) genotype
*3/*3
|
0 participants
n=5 Participants
|
35 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
Thymidylate Synthase Enhancer Region (TSER) genotype
*3/*4
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Performance status
0
|
63 participants
n=5 Participants
|
26 participants
n=7 Participants
|
89 participants
n=5 Participants
|
|
Performance status
1
|
34 participants
n=5 Participants
|
11 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Performance status
2
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Baseline Stage
Stage IIA (T3, N0, M0)
|
24 participants
n=5 Participants
|
10 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Baseline Stage
Stage IIB (T4, N0, M0)
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Baseline Stage
Stage IIIA (T1-2, N1, M0)
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Baseline Stage
Stage IIIB (T3-4, N1, M0)
|
53 participants
n=5 Participants
|
19 participants
n=7 Participants
|
72 participants
n=5 Participants
|
|
Baseline Stage
Stage IIIC (T-any, N2, M0)
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Baseline Stage
Stage IV (T-any, N-any, M1)
|
14 participants
n=5 Participants
|
5 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Baseline clinical T stage
T1-2
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Baseline clinical T stage
T3
|
77 participants
n=5 Participants
|
32 participants
n=7 Participants
|
109 participants
n=5 Participants
|
|
Baseline clinical T stage
T4
|
19 participants
n=5 Participants
|
5 participants
n=7 Participants
|
24 participants
n=5 Participants
|
|
Baseline clinical N stage
N0
|
30 participants
n=5 Participants
|
11 participants
n=7 Participants
|
41 participants
n=5 Participants
|
|
Baseline clinical N stage
N1
|
64 participants
n=5 Participants
|
22 participants
n=7 Participants
|
86 participants
n=5 Participants
|
|
Baseline clinical N stage
N2
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Baseline clinical M stage
M0
|
84 participants
n=5 Participants
|
32 participants
n=7 Participants
|
116 participants
n=5 Participants
|
|
Baseline clinical M stage
M1
|
14 participants
n=5 Participants
|
5 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Clinical staging modality
Endoscopic ultrasound
|
60 participants
n=5 Participants
|
21 participants
n=7 Participants
|
81 participants
n=5 Participants
|
|
Clinical staging modality
CT Scan +/- PET Scan
|
22 participants
n=5 Participants
|
6 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Clinical staging modality
MRI
|
16 participants
n=5 Participants
|
10 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Tumor distance from anal verge (cm)
<5
|
33 participants
n=5 Participants
|
12 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Tumor distance from anal verge (cm)
5-10
|
57 participants
n=5 Participants
|
21 participants
n=7 Participants
|
78 participants
n=5 Participants
|
|
Tumor distance from anal verge (cm)
>10
|
8 participants
n=5 Participants
|
4 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Tumor grade
Well differentiated
|
8 participants
n=5 Participants
|
4 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Tumor grade
Moderately differentiated
|
68 participants
n=5 Participants
|
25 participants
n=7 Participants
|
93 participants
n=5 Participants
|
|
Tumor grade
Poorly differentiated
|
17 participants
n=5 Participants
|
7 participants
n=7 Participants
|
24 participants
n=5 Participants
|
|
Tumor grade
Not reported
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 year after enrollmentPopulation: 8 not evaluable in Good Risk arm-(1)death before surgery (1)clinical CR w/o surgery (1)refused surgery (2)not resectable (2)withdrew consent (1)delayed surgery and given FOLFOX 6 not evaluable in Poor Risk arm-(1) death prior to surgery (1)clinical CR no surgery (1)refused surgery (2)withdrew consent (1)not given irinotecan by treating physician
Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1. Historical studies demonstrate a DS rate of 45%.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=90 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=31 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Rate of Tumor Downstaging Compared With Historical Controls.
|
64.4 percentage of participants
Interval 54.1 to 74.6
|
64.5 percentage of participants
Interval 43.7 to 78.9
|
SECONDARY outcome
Timeframe: 1 year after enrollmentPopulation: 8 not evaluable in Good Risk arm-(1)death before surgery (1)clinical CR w/o surgery (1)refused surgery (2)not resectable (2)withdrew consent (1)delayed surgery and given FOLFOX 6 not evaluable in Poor Risk arm-(1) death prior to surgery (1)clinical CR no surgery (1)refused surgery (2)withdrew consent (1)not given irinotecan by treating physician
Complete tumor response is defined as the absence of any viable tumor in the rectum (ypT0). Pathologic complete response (pCR) is defined as the absence of any viable tumor in the rectum or in the perirectal lymph nodes (ypT0N0). pCR rate of historical controls is 8%-14%.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=90 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=31 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Complete Response Rates
ypT0
|
20 percentage of participants
|
41.9 percentage of participants
|
|
Complete Response Rates
pCR
|
18.9 percentage of participants
|
35.5 percentage of participants
|
SECONDARY outcome
Timeframe: Prior to start of study treatment and 3-6 weeks post completion of radiation therapyPopulation: The data was not collected for this outcome measure as the questionnaire was encouraged but not required.
The questionnaire is encouraged but not required.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Prior to start of study treatment and 3-6 weeks post completion of radiation therapyPopulation: The data was not collected for this outcome measure as the questionnaire was encouraged but not required.
The questionnaire is encouraged but not required.
Outcome measures
Outcome data not reported
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: Two of the patients in the Good Risk arm withdrew consent and are not included. Two of the patients in the Poor Risk arm withdrew consent and are not included.
Grade 3 to 4 toxicities related to treatment and surgery using CTC Version 2.0.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=96 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=35 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Nausea
|
0 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Vomiting
|
0 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Diarrhea
|
17 participants
|
16 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Dehydration
|
3 participants
|
7 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Mucositis
|
4 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
GI bleed
|
2 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Ileitis
|
0 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Enteritis
|
1 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Dyspnea
|
1 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Neutropenia
|
0 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Anemia
|
3 participants
|
3 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Pain
|
3 participants
|
4 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Perforation
|
2 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Pelvic abscess
|
0 participants
|
2 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
PPE
|
0 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Crohn's flare
|
1 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Syncope
|
2 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Rash
|
2 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Fatigue
|
1 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Atrial fibrillation
|
1 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Infection
|
1 participants
|
1 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Headache
|
1 participants
|
0 participants
|
|
Toxicities by Genotype Group (Good Risk Versus Poor Risk)
Small bowel obstruction
|
1 participants
|
0 participants
|
POST_HOC outcome
Timeframe: 1 year, 2 years, and 3 yearsPopulation: Two of the patients in the Good Risk arm withdrew consent and are not included. Two of the patients in the Poor Risk arm withdrew consent and are not included.
Analyzed using Kaplan-Meier Models.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=96 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=35 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Overall Survival
1 year
|
96.9 percentage of participants
|
94.3 percentage of participants
|
|
Overall Survival
2 years
|
80.6 percentage of participants
|
94.3 percentage of participants
|
|
Overall Survival
3 years
|
78.2 percentage of participants
|
83.6 percentage of participants
|
POST_HOC outcome
Timeframe: 1 year, 2 years, and 3 yearsPopulation: 14 patients in the Good Risk arm had metastatic rectal cancer at time of enrollment are not included in this analyses. 3 patients in the Poor Risk arm had metastatic rectal disease before surgery and are included in this analyses. 2 of the patients in the Good Risk arm and Poork Risk arm withdrew consent and are not included.
Analyzed using Kaplan-Meier Models.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=82 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=32 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Relapse-free Survival
1 year
|
85.2 percentage of participants
|
87.0 percentage of participants
|
|
Relapse-free Survival
2 years
|
78.3 percentage of participants
|
80.5 percentage of participants
|
|
Relapse-free Survival
3 years
|
73.4 percentage of participants
|
72.4 percentage of participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Good Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. MTHFR gene = methylenetetrahydrofolate reductase (NAD(P)H)
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=75 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=21 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CC (MTHFR 677C>T)
|
34 participants
|
5 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CT (MTHFR 677C>T)
|
34 participants
|
12 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
TT (MTHFR 677C>T)
|
7 participants
|
4 participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=19 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=16 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CC (MTHFR 677C>T)
|
12 participants
|
9 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CT (MTHFR 677C>T)
|
6 participants
|
7 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
TT (MTHFR 677C>T)
|
1 participants
|
0 participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Good Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=75 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=21 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
AA (MTHFR 1298A>C)
|
26 participants
|
15 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
AC (MTHFR 1298A>C)
|
41 participants
|
4 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CC (MTHFR 1298A>C)
|
8 participants
|
2 participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=19 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=16 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
AA (MTHFR 1298A>C)
|
9 participants
|
8 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
AC (MTHFR 1298A>C)
|
9 participants
|
6 participants
|
|
Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CC (MTHFR 1298A>C)
|
1 participants
|
2 participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Good Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=75 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=21 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
677C-1298A
|
33 participants
|
12 participants
|
|
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
677C-1298C
|
49 participants
|
6 participants
|
|
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
677T-1298A
|
40 participants
|
16 participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=19 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=16 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
677C-1298A
|
15 participants
|
11 participants
|
|
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
677C-1298C
|
10 participants
|
8 participants
|
|
Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
677T-1298A
|
7 participants
|
7 participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Good Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=75 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=21 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CA-CA
|
13 participants
|
2 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CA-CC
|
14 participants
|
1 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CA-TA
|
6 participants
|
9 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CC-CC
|
7 participants
|
2 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CC-TA
|
27 participants
|
3 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
CC-TC
|
1 participants
|
0 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)
TA-TA
|
7 participants
|
4 participants
|
POST_HOC outcome
Timeframe: First day of treatment through 30 days after completion of surgeryPopulation: 2 of the patients in the Poor Risk arm withdrew consent and are not included.
Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit.
Outcome measures
| Measure |
Good Risk (TYMS*2/*2, *2/*3, *2/*4)
n=19 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (TYMS*3/*3, *3/*4)
n=16 Participants
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CC-TC
|
0 participants
|
0 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CA-CA
|
4 participants
|
4 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CA-CC
|
7 participants
|
3 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CA-TA
|
4 participants
|
4 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CC-CC
|
1 participants
|
2 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
CC-TA
|
2 participants
|
3 participants
|
|
Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)
TA-TA
|
1 participants
|
0 participants
|
Adverse Events
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)
Serious events: 16 serious events
Other events: 96 other events
Deaths: 0 deaths
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)
Serious events: 12 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)
n=96 participants at risk
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)
n=35 participants at risk
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Diarrhea/RT enteritis
|
7.3%
7/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
20.0%
7/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Perforation/abscess/leak fistula
|
2.1%
2/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Cardiac disorders
Atrial fibrillation
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Gastrointestinal bleed
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Blood and lymphatic system disorders
Anemia-blood transfusion
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Injury, poisoning and procedural complications
Hernia repair
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Crohn's flare
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Cardiac disorders
Aneurysmal bleed
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
Other adverse events
| Measure |
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)
n=96 participants at risk
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)
n=35 participants at risk
Radiation 45 Gy in 25 fractions to the pelvis.
5FU CIVI 225 mg/m2/day by CIVI during radiation
Irinotecan 50 mg/m2 IV weekly for 5 doses.
Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.
|
|---|---|---|
|
Investigations
Leukocytes (total WBC)
|
31.2%
30/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
57.1%
20/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Platelets
|
12.5%
12/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
68.8%
66/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
85.7%
30/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
8.3%
8/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
31.4%
11/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Lymphopenia
|
91.7%
88/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
91.4%
32/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Nausea
|
26.0%
25/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
54.3%
19/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
12/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
22.9%
8/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Diarrhea
|
75.0%
72/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
74.3%
26/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Constipation
|
7.3%
7/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
17.1%
6/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Dehydration
|
6.2%
6/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
17.1%
6/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Indigestion/cramping
|
13.5%
13/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
28.6%
10/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Heartburn
|
2.1%
2/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Tenesmus
|
13.5%
13/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Rectal spasms
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Flatus
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Stomatitis/mucositis
|
35.4%
34/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
28.6%
10/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Anorexia
|
16.7%
16/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
34.3%
12/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Ileitis/Ileus
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Bleeding-GI
|
17.7%
17/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
11.4%
4/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Dry mouth
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Bilirubin - increased
|
27.1%
26/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
34.3%
12/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
SGOT/SGPT - increased
|
18.8%
18/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
37.1%
13/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Alkaline phosphatase - increased
|
12.5%
12/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
20.0%
7/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
BUN - increased
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Creatinine -increased
|
19.8%
19/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
17.1%
6/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Renal and urinary disorders
Dysuria
|
14.6%
14/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
11.4%
4/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Renal and urinary disorders
Incontinence
|
6.2%
6/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Renal and urinary disorders
Proteinuria
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Renal and urinary disorders
Nocturia
|
5.2%
5/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccoughs
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Vascular disorders
Hypertension
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
8.6%
3/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
General disorders
Edema
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Nervous system disorders
Neuropathy - motor
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Nervous system disorders
Neuropathy-sensory
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Nervous system disorders
Dizziness
|
2.1%
2/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
11.4%
4/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Nervous system disorders
Syncope
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Psychiatric disorders
Mood alteration-depression
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Psychiatric disorders
Mood alteration-anxiety
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Nervous system disorders
Seizure
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Nervous system disorders
Tremors
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
General disorders
Chills
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
General disorders
Fever without infection
|
2.1%
2/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
8.6%
3/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Sweats
|
4.2%
4/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
General disorders
Fatigue
|
28.1%
27/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
62.9%
22/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Weight loss
|
10.4%
10/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
14.3%
5/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Psychiatric disorders
Insomnia
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
11.4%
4/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
16/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
17.1%
6/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
9.4%
9/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
37.1%
13/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
9.4%
9/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
22.9%
8/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypernatremia
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
13.5%
13/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
31.4%
11/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
13.5%
13/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
37.1%
13/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Metabolism and nutrition disorders
Hypoprotenemia
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Skin and subcutaneous tissue disorders
Skin itching/irritation/rash/desquamation
|
52.1%
50/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
48.6%
17/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Skin and subcutaneous tissue disorders
Skin dryness
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
2.1%
2/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Vascular disorders
Flushing
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Skin and subcutaneous tissue disorders
Erythema/PPE
|
20.8%
20/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
11.4%
4/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Skin and subcutaneous tissue disorders
Hand-foot syndrome
|
7.3%
7/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Infections and infestations
Infection
|
4.2%
4/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
11.4%
4/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Infections and infestations
Abscess
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
PT
|
5.2%
5/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
5.7%
2/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
PTT
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Investigations
Defibrillator malfunction
|
1.0%
1/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
0.00%
0/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Gastrointestinal disorders
Pain-rectum
|
52.1%
50/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
68.6%
24/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Nervous system disorders
Pain-head, headache
|
2.1%
2/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Eye disorders
Ocular/vision-eye discomfort
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.1%
3/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
|
Vascular disorders
Hypotension
|
0.00%
0/96 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
2.9%
1/35 • Beginning of treatment through 30 days after the end of surgery.
Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included.
|
Additional Information
Benjamin R. Tan, M.D.
Washington University School of Medicine
Phone: 314-362-3560
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place