Trial Outcomes & Findings for Combination Chemotherapy and Radiation Therapy With/Without Surgery In Patients With Stage II/III Bladder Cancer (NCT NCT00055601)

Last Updated: 2018-06-15

Results Overview

Radiation therapy and chemotherapy per protocol or within acceptable variation guidelines based on central review. The study was designed for a two-sided binomial test with 87% power and a significance level of 0.05 with a null hypothesis of a 70% completion rate against the alternative 90% completion rate. For each arm, more than 34 out of 43 evaluable patients completing the treatment, would indicate to reject the null hypothesis for a better treatment completion rate. Fewer than 24 out 43 evaluable patients completing the treatment would indicate to reject the null hypothesis for a worse treatment completion rate. Otherwise, the conclusion would be that there is not enough evidence to reject the null hypothesis of a 70% completion rate in either direction.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

97 participants

Primary outcome timeframe

From randomization to 11 weeks

Results posted on

2018-06-15

Participant Flow

Participant milestones

Participant milestones
Measure	Pelvic RT + Paclitaxel + Cisplatin Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.
Overall Study STARTED	48	49
Overall Study COMPLETED	46	47
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Pelvic RT + Paclitaxel + Cisplatin Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.
Overall Study Protocol Violation	1	1
Overall Study No protocol treatment received	1	1

Baseline Characteristics

Combination Chemotherapy and Radiation Therapy With/Without Surgery In Patients With Stage II/III Bladder Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pelvic RT + Paclitaxel + Cisplatin n=46 Participants Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin n=47 Participants Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Total n=93 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	67 years n=7 Participants	66 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	40 Participants n=7 Participants	78 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to 11 weeks

Population: All eligible patients who started study treatment.

Outcome measures

Outcome measures
Measure	Pelvic RT + Paclitaxel + Cisplatin n=46 Participants Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin n=47 Participants Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.
Treatment Completion Rate	67 percentage of participants Interval 51.0 to 80.0	53 percentage of participants Interval 38.0 to 68.0

SECONDARY outcome

Timeframe: From randomization to eight weeks

Population: All eligible patients who started study treatment

Complete response requires the absence of any tumor in the tumor-site biopsy specimen or elsewhere and a bimanual exam that does not indicate the presence of a tumor mass.

Outcome measures

Outcome measures
Measure	Pelvic RT + Paclitaxel + Cisplatin n=46 Participants Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin n=47 Participants Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.
Complete Response After Induction	72 percentage of participants Interval 57.0 to 84.0	62 percentage of participants Interval 46.0 to 76.0

SECONDARY outcome

Timeframe: From the date of randomization to five years.

Population: All eligible patients who started study treatment

Bladder-intact survival was measured from the date of randomization to occurrence of cystectomy or death. Five-year rates were estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Pelvic RT + Paclitaxel + Cisplatin n=46 Participants Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin n=47 Participants Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.
Bladder-intact Survival Rate (5 Years)	67 percentage of participants Interval 53.0 to 81.0	71 percentage of participants Interval 57.0 to 84.0

Adverse Events

Pelvic RT + Paclitaxel + Cisplatin

Serious events: 43 serious events

Other events: 46 other events

Deaths: 0 deaths

Pelvic RT + Fluorouracil + Cisplatin

Serious events: 39 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pelvic RT + Paclitaxel + Cisplatin n=46 participants at risk Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin n=47 participants at risk Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.
Blood and lymphatic system disorders Febrile neutropenia	4.3% 2/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
Blood and lymphatic system disorders Hematologic-Other	6.5% 3/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Blood and lymphatic system disorders Hemoglobin decreased	10.9% 5/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
Blood and lymphatic system disorders Hemoglobin for leukemia	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Blood and lymphatic system disorders Packed red blood cell transfusion	13.0% 6/46 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-serious adverse events (AE).	12.8% 6/47 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-serious adverse events (AE).
Blood and lymphatic system disorders Platelet transfusion	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Cardiac disorders Circulatory or cardiac-Other	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Cardiac disorders Edema NOS	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Cardiac disorders Sinus bradycardia	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Cardiac disorders Sinus tachycardia	2.2% 1/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
Cardiac disorders Supraventricular arrhythmia NOS	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Cardiac disorders Ventricular arrhythmia NOS	2.2% 1/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
Gastrointestinal disorders Diarrhea NOS	2.2% 1/46 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-serious adverse events (AE).	4.3% 2/47 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-serious adverse events (AE).
Gastrointestinal disorders Melaena	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
General disorders Chest pain	2.2% 1/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
General disorders Constitutional symptons-Other	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
General disorders Fatigue	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
General disorders Pain-other	2.2% 1/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
Infections and infestations Culture wound positive	0.00% 0/46 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-serious adverse events (AE).	4.3% 2/47 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-serious adverse events (AE).
Infections and infestations Infection NOS	2.2% 1/46 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-serious adverse events (AE).	8.5% 4/47 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-serious adverse events (AE).
Infections and infestations Infection with grade 3 or 4 neutropenia	0.00% 0/46 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-serious adverse events (AE).	4.3% 2/47 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-serious adverse events (AE).
Infections and infestations Infection with unknown ANC	4.3% 2/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Investigations Alanine aminotransferase increased	4.3% 2/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Investigations Aspartate aminotransferase increased	2.2% 1/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
Investigations Blood creatinine increased	2.2% 1/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
Investigations Leukopenia NOS	17.4% 8/46 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-serious adverse events (AE).	21.3% 10/47 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-serious adverse events (AE).
Investigations Lymphopenia	8.7% 4/46 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-serious adverse events (AE).	21.3% 10/47 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-serious adverse events (AE).
Investigations Neutropenia	58.7% 27/46 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-serious adverse events (AE).	38.3% 18/47 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-serious adverse events (AE).
Investigations Neutrophils/granulocytes for leukemia	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Investigations Platelet count decreased	34.8% 16/46 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-serious adverse events (AE).	23.4% 11/47 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-serious adverse events (AE).
Investigations Weight increased	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Anorexia	2.2% 1/46 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-serious adverse events (AE).	4.3% 2/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Blood magnesium decreased	10.9% 5/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Dehydration	2.2% 1/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Hyperglycemia NOS	17.4% 8/46 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-serious adverse events (AE).	10.6% 5/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Hypocalcemia	2.2% 1/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Hypoglycaemia NOS	4.3% 2/46 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-serious adverse events (AE).	0.00% 0/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Hypokalemia	2.2% 1/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Metabolism and nutrition disorders Hyponatremia	4.3% 2/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).

Other adverse events
Measure	Pelvic RT + Paclitaxel + Cisplatin n=46 participants at risk Induction: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with paclitaxel and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.	Pelvic RT + Fluorouracil + Cisplatin n=47 participants at risk Induction: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin; Consolidation: Twice-daily pelvic radiation therapy with fluoruracil and cisplatin if tumor response is T0/Ta/Tis or radical cystectomy if tumor response is ≥ T1; Adjuvant: gemcitabine, paclitaxel, and cisplatin IV.
Blood and lymphatic system disorders Hemolysis NOS	6.5% 3/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Cardiac disorders Circulatory or cardiac-Other	8.7% 4/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Blood and lymphatic system disorders Hematologic-Other	56.5% 26/46 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-serious adverse events (AE).	40.4% 19/47 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-serious adverse events (AE).
Blood and lymphatic system disorders Hemoglobin decreased	93.5% 43/46 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-serious adverse events (AE).	91.5% 43/47 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-serious adverse events (AE).
Cardiac disorders Edema NOS	15.2% 7/46 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-serious adverse events (AE).	14.9% 7/47 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-serious adverse events (AE).
Cardiac disorders Palpitations	2.2% 1/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
Ear and labyrinth disorders Hearing impaired	8.7% 4/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Gastrointestinal disorders Abdominal pain NOS	23.9% 11/46 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-serious adverse events (AE).	14.9% 7/47 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-serious adverse events (AE).
Gastrointestinal disorders Constipation	39.1% 18/46 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-serious adverse events (AE).	46.8% 22/47 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-serious adverse events (AE).
Gastrointestinal disorders Diarrhea (with colostomy)	2.2% 1/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
Gastrointestinal disorders Diarrhea NOS	71.7% 33/46 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-serious adverse events (AE).	76.6% 36/47 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-serious adverse events (AE).
Gastrointestinal disorders Dyspepsia	10.9% 5/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
Gastrointestinal disorders Flatulence	6.5% 3/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Gastrointestinal disorders GI-other	19.6% 9/46 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-serious adverse events (AE).	8.5% 4/47 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-serious adverse events (AE).
Gastrointestinal disorders Late RT toxicity: Bowel: NOS	13.0% 6/46 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-serious adverse events (AE).	10.6% 5/47 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-serious adverse events (AE).
Gastrointestinal disorders Nausea	58.7% 27/46 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-serious adverse events (AE).	59.6% 28/47 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-serious adverse events (AE).
Gastrointestinal disorders Proctalgia	2.2% 1/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
Gastrointestinal disorders Proctitis NOS	4.3% 2/46 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-serious adverse events (AE).	8.5% 4/47 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-serious adverse events (AE).
Gastrointestinal disorders Rectal bleeding	13.0% 6/46 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-serious adverse events (AE).	2.1% 1/47 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-serious adverse events (AE).
Gastrointestinal disorders Stomatitis	4.3% 2/46 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-serious adverse events (AE).	12.8% 6/47 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-serious adverse events (AE).
Gastrointestinal disorders Vomiting NOS	15.2% 7/46 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-serious adverse events (AE).	34.0% 16/47 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-serious adverse events (AE).
General disorders Chest pain	2.2% 1/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
General disorders Constitutional symptons-Other	2.2% 1/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
General disorders Fatigue	89.1% 41/46 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-serious adverse events (AE).	93.6% 44/47 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-serious adverse events (AE).
General disorders Injection site reaction NOS	4.3% 2/46 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-serious adverse events (AE).	6.4% 3/47 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-serious adverse events (AE).
General disorders Late RT toxicity: Other: NOS	26.1% 12/46 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-serious adverse events (AE).	17.0% 8/47 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-serious adverse events (AE).
General disorders Pain-other	21.7% 10/46 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-serious adverse events (AE).	23.4% 11/47 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-serious adverse events (AE).
General disorders Pyrexia	13.0% 6/46 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-serious adverse events (AE).	8.5% 4/47 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-serious adverse events (AE).
General disorders Rigors	6.5% 3/46 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-serious adverse events (AE).	10.6% 5/47 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-serious adverse events (AE).
Hepatobiliary disorders Hepatic-Other	10.9% 5/46 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-serious adverse events (AE).	12.8% 6/47 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-serious adverse events (AE).
Infections and infestations Infection NOS	4.3% 2/46 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-serious adverse events (AE).	10.6% 5/47 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-serious adverse events (AE).
Investigations Alanine aminotransferase increased	26.1% 12/46 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-serious adverse events (AE).	21.3% 10/47 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-serious adverse events (AE).
Investigations Aspartate aminotransferase increased	21.7% 10/46 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-serious adverse events (AE).	21.3% 10/47 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-serious adverse events (AE).
Investigations Blood alkaline phosphatase NOS increased	17.4% 8/46 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-serious adverse events (AE).	19.1% 9/47 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-serious adverse events (AE).
Investigations Blood bilirubin increased	15.2% 7/46 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-serious adverse events (AE).	12.8% 6/47 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-serious adverse events (AE).
Investigations Blood creatinine increased	45.7% 21/46 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-serious adverse events (AE).	36.2% 17/47 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-serious adverse events (AE).
Investigations Leukopenia NOS	89.1% 41/46 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-serious adverse events (AE).	78.7% 37/47 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-serious adverse events (AE).
Investigations Lymphopenia	17.4% 8/46 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-serious adverse events (AE).	17.0% 8/47 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-serious adverse events (AE).
Investigations Metabolic-Other	26.1% 12/46 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-serious adverse events (AE).	10.6% 5/47 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-serious adverse events (AE).
Investigations Neutropenia	34.8% 16/46 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-serious adverse events (AE).	38.3% 18/47 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-serious adverse events (AE).