Trial Outcomes & Findings for Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage III Non-Small Cell Lung Cancer (NCT NCT00023673)

Last Updated: 2017-12-22

Results Overview

Dose limiting toxicity (DLT) = Grade 3/4 non-hematologic toxicities (excluding nausea, vomiting, and alopecia) and Grade 4 hematologic toxicities. The DLT rate for this study was set at 40% based on Radiation Therapy Oncology Group (RTOG) study 94-10. No acute (within 90 days from start of 3DRT) DLT's in the first 5 patients (0/5) or the combination of one acute DLT in the first 5 patients (1/5) and none in the next 2 patients (0/2) was required to deem a given dose level to be acceptable. If at any time a Grade 5 toxicity (death) occurred, accrual would be suspended and the event reviewed by a study chair. At any given dose level, this design gives at least 90% confidence that the true acute DLT rate is less than 40% and the probability of not escalating when the true toxicity rate is 40% or higher is at least 83%. Rating scale: 0 = not the MTD, 1 = MTD

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

63 participants

Primary outcome timeframe

From start of treatment to 90 days

Results posted on

2017-12-22

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase II: 74 Gy/37 fx + Chemotherapy Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Overall Study STARTED	8	9	46
Overall Study COMPLETED	8	9	44
Overall Study NOT COMPLETED	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 70 Gy/35 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase II: 74 Gy/37 fx + Chemotherapy Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Overall Study Ineligible / no protocol treatment	0	0	0	1
Overall Study Patient withdrew consent	0	0	0	1

Baseline Characteristics

Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage III Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=8 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy n=9 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase II: 74 Gy/37 fx + Chemotherapy n=44 Participants Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Total n=61 Participants Total of all reporting groups
Age, Continuous	65.5 years n=5 Participants	68 years n=7 Participants	67 years n=5 Participants	67 years n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	1 Participants n=7 Participants	37 Participants n=5 Participants	45 Participants n=4 Participants

PRIMARY outcome

Timeframe: From start of treatment to 90 days

Population: The first seven eligible patients who started protocol treatment at each dose level.

Outcome measures

Outcome measures
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=7 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy n=7 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy	0 units on a scale	1 units on a scale

PRIMARY outcome

Timeframe: From registration to 1 year

Population: Eligible patients at the MTD dose level who started protocol treatment.

Null hypothesis: p\<= 62.3% (the best arm of RTOG 94-10); alternative hypothesis: p\>= 77.9%. Where p is the percentage of patients alive at at 12 months. Using a one-group chi-square test with alpha = 0.10, a sample size of 50 patients provides at least 87% power to detect a 25% or greater relative increase in the 12-month survival rate, or equivalently, an absolute increase of at least 15.6 percentage points (62.3 versus 77.9). If the point estimate is greater than 71.1% (upper bound), then the conclusion is that the 12-month survival rate from the new treatment significantly improved from 62.3%.

Outcome measures

Outcome measures
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=53 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Percentage of Patients Who Survive at Least 12 Months	75.5 percentage of participants Interval 61.5 to 85.0	—

SECONDARY outcome

Timeframe: Chemotherapy/Acute RT toxicity: from start of treatment to 90 days from start of study treatment; Late RT toxicity: from 90 days after start of treatment to last follow-up (Maximum follow-up = 57.9 months.)

Population: Eligible patients from Phase I and II 74 Gy arms who started study treatment. Additionally for late RT toxicity, those who have toxicity data at least 90 days from start of RT.

Highest grade toxicity per subject was counted. Toxicities were graded using the Common Toxicity Criteria (CTC) v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.Chemotherapy/Acute RT toxicities occur during chemotherapy and/or within 90 days of the start of RT. Late RT toxicities occur more than 90 days after the start of RT.

Outcome measures

Outcome measures
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=53 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT non-hematologic: Grade 1	4 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT non-hematologic: Grade 2	16 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT non-hematologic: Grade 3	28 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT non-hematologic: Grade 4	2 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT non-hematologic: Grade 5	2 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT hematologic: Grade 1	1 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT hematologic: Grade 2	8 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT hematologic: Grade 3	37 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT hematologic: Grade 4	5 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Chemotherapy/Acute RT hematologic: Grade 5	2 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Late RT toxicity: Grade 1	13 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Late RT toxicity: Grade 2	10 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Late RT toxicity: Grade 3	9 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Late RT toxicity: Grade 4	1 Participants	—
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. Late RT toxicity: Grade 5	1 Participants	—

SECONDARY outcome

Timeframe: From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)

Population: All eligible patients on the phase I and II 74 Gy arms who received treatment and had RT plan data available with the given structure

Percent volume of total lung receiving \> 20 Gy radiation therapy (Lung V20) was compared between the two patient groups of those who experienced a grade 3 and higher lung toxicity and those who did not. Similarly, it was also compared between the two patient groups of those who experienced a grade 2 and higher esophageal toxicity and those who did not. Toxicities graded using CTC v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.

Outcome measures

Outcome measures
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=53 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy n=53 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level) Lung Toxicity: Lung V20	24.1 Percent (V20) Interval 9.9 to 35.7	26.3 Percent (V20) Interval 15.6 to 33.3
Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level) Esophagitis Toxicity: Lung V20	22.4 Percent (V20) Interval 9.9 to 35.7	26.3 Percent (V20) Interval 14.0 to 33.3

SECONDARY outcome

Timeframe: From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)

Population: All eligible patients on the phase I and II 74 Gy arms who received treatment and had RT plan data available with the given structure

Mean lung dose was compared between the two patient groups of those who experienced a grade 3 and higher lung toxicity and those who did not. Similarly, mean lung dose, and mean esophageal dose were compared between the two patient groups of those who experienced a grade 2 and higher esophageal toxicity and those who did not. Toxicities graded using CTC v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.

Outcome measures

Outcome measures
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=53 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy n=53 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level) Lung Toxicity: Mean Lung Dose	15.2 Gy (mean dose) Interval 5.7 to 21.8	17.2 Gy (mean dose) Interval 11.5 to 18.9
Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level) Esophagitis Toxicity: Mean Lung Dose	14.5 Gy (mean dose) Interval 5.7 to 21.8	16.9 Gy (mean dose) Interval 9.9 to 20.6
Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level) Esophagitis Toxicity: Mean Esophageal Dose	21.0 Gy (mean dose) Interval 7.1 to 34.9	24.6 Gy (mean dose) Interval 16.2 to 33.7

SECONDARY outcome

Timeframe: From start of treatment until 3 months after completion of all study treatment, estimated to be 5 or 6.5 months depending whether or not subject received optional adjuvant chemotherapy.

Population: Eligible patients from Phase I and II 74 Gy arms who started study treatment.

"Complete response" means no evidence of tumor on the CT scan.

Outcome measures

Outcome measures
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=53 Participants Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I: 74 Gy/37 fx + Chemotherapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Number of Patients With Complete Response at 3 Months After Completion of Therapy	3 Participants	—

Adverse Events

Phase I: 75.25 Gy/36 fx + Chemotherapy

Serious events: 7 serious events

Other events: 8 other events

Deaths: 0 deaths

Phase I/II: 74 Gy/37 fx + Chemotherapy

Serious events: 36 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld

Radiation Therapy Oncology Group

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=8 participants at risk Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I/II: 74 Gy/37 fx + Chemotherapy n=53 participants at risk Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
Blood and lymphatic system disorders Hemoglobin decreased	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Blood and lymphatic system disorders Hemolysis NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Blood and lymphatic system disorders Packed red blood cell transfusion	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Blood and lymphatic system disorders Platelet transfusion	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Cardiac disorders Arrhythmia NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Cardiac disorders Sinus tachycardia	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Cardiac disorders Supraventricular arrhythmia NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Dyspepsia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Dysphagia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Esophageal spasm	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	5.7% 3/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Esophagitis NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders GI-other	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Ileus	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Nausea	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Vomiting NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Esophagus	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	7.5% 4/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Heart	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Lung	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	15.1% 8/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Other	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Pain-other	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Immune system disorders Hypersensitivity NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Infections and infestations Infection NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.4% 5/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Infections and infestations Infection with grade 3 or 4 neutropenia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Infections and infestations Infection with unknown ANC	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Infections and infestations Infection, Other	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Injury, poisoning and procedural complications Dermatitis radiation NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Injury, poisoning and procedural complications Operative injury of vein/artery	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Cardiac troponin I increased	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Leukopenia NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	35.8% 19/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Lymphopenia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Neutropenia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Anorexia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Dehydration	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	5.7% 3/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Hyperglycemia NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	7.5% 4/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Metabolism and nutrition disorders Hypokalemia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Musculoskeletal and connective tissue disorders Muscle weakness NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Nervous system disorders Convulsions NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Nervous system disorders Syncope	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Renal and urinary disorders Renal failure NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Renal and urinary disorders Renal/GU-Other	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).

Other adverse events
Measure	Phase I: 75.25 Gy/36 fx + Chemotherapy n=8 participants at risk Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.	Phase I/II: 74 Gy/37 fx + Chemotherapy n=53 participants at risk Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
General disorders Late RT Toxicity: Esophagus	50.0% 4/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	17.0% 9/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Bone	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Gastritis NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Nausea	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	32.1% 17/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Radiation mucositis	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	7.5% 4/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Rectal bleeding	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	0.00% 0/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Stomatitis	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	7.5% 4/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Gastrointestinal disorders Vomiting NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	17.0% 9/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Chest pain	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	5.7% 3/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Edema NOS	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Fatigue	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	75.5% 40/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Heart	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	7.5% 4/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Lung	62.5% 5/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	49.1% 26/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Other	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	15.1% 8/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Skin (within the irradiated field)	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.4% 5/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Spinal cord	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Late RT Toxicity: Subcutaneous tissue	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Pain due to radiation	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	20.8% 11/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Pain-other	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	24.5% 13/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Pyrexia	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	17.0% 9/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
General disorders Rigors	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Hepatobiliary disorders Hepatic-Other	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	7.5% 4/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Immune system disorders Hypersensitivity NOS	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Infections and infestations Infection NOS	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Infections and infestations Infection with unknown ANC	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Injury, poisoning and procedural complications Dermatitis radiation NOS	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	26.4% 14/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Activated partial thromboplastin time prolonged	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Alanine aminotransferase increased	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	11.3% 6/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Aspartate aminotransferase increased	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Blood alkaline phosphatase NOS increased	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	5.7% 3/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Blood bilirubin increased	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Blood creatine phosphokinase increased	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Blood creatinine increased	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	9.4% 5/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Forced expiratory volume decreased	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	1.9% 1/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Leukopenia NOS	75.0% 6/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	54.7% 29/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Lymphopenia	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	32.1% 17/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Metabolic-Other	0.00% 0/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	3.8% 2/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Neutropenia	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	47.2% 25/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Platelet count decreased	25.0% 2/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	37.7% 20/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).
Investigations Prothrombin time prolonged	12.5% 1/8 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).	5.7% 3/53 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-SAE adverse events (AE).