S0219, Combination Chemotherapy Followed By Observation or Surgery in Patients With Stage II or Stage III Cancer of the Urothelium

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00045630
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 77
• Locations: 128
• Arm: 1
• Duration (Months): 107
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells and decrease the need for surgery.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by observation or surgery to remove the bladder (cystectomy) in treating patients who have stage II or stage III cancer of the urothelium.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Urethral Cancer	Drug: carboplatin; Drug: gemcitabine; Drug: paclitaxel; Procedure: surgery	Phase 2

Detailed Description

OBJECTIVES:

• Determine the pathologic complete response of patients with stage II or III transitional cell cancer of the urothelium treated with neoadjuvant gemcitabine, paclitaxel, and carboplatin followed by observation or immediate cystectomy.

• Determine, preliminarily, if molecular markers predict response, survival, and tumor recurrence in patients treated with these regimens.

• Determine recurrence rates and cystectomy-free survival of patients who choose observation after an initial response to neoadjuvant chemotherapy.

• Compare the survival of patients treated with neoadjuvant chemotherapy followed by cystectomy vs observation.

• Determine the feasibility, tolerability, and toxicity of these regimens in these patients.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes and paclitaxel IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Within 4-8 weeks after completion of neoadjuvant chemotherapy, patients undergo a third transurethral resection of bladder tumor.

Patients with T0 disease after neoadjuvant chemotherapy may choose to undergo observation. These patients undergo cystoscopies with biopsies every 3 months for 1 year, every 4 months for 1 year, and then every 6 months until disease progression.

Patients with T1 disease or greater after neoadjuvant chemotherapy undergo immediate cystectomy. Patients with T0 disease may also choose this option. Patients undergoing immediate cystectomy are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study within 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Sequential Approach to the Treatment of Muscle Invasive, Non-Metastatic Urothelial Carcinoma of the Bladder: A Phase II Trial of Neoadjuvant Gemcitabine, Paclitaxel and Carboplatin With Molecular Correlates
• Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine, Paclitaxel, Carboplatin Gemcitabine, Paclitaxel, Carboplatin followed by surgery	Drug: carboplatin; Drug: gemcitabine; Other Names: gemcitabine hydrochloride ; Drug: paclitaxel; Other Names: Taxol ; Procedure: surgery

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy [up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )]

   Pathologic complete response (CR) is defined as absence of viable tumor in the TURBT specimen. Stable/No Response is defined as at least some disease evaluation tests were done (same tests as baseline) and status does not qualify for CR or Progression. Progression is defined as one or more of the following must occur: unequivocal progression of disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without documented progression or symptomatic deterioration.

Secondary Outcome Measures

1. Overall Survival (OS) [0-2 years]

   Overall survival is defined from the date of registration to date of death from any cause

2. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [Patients were assessed for adverse events at weeks 1, 2, 4, 5, 7, 8, and following surgery]

   Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed muscle-invasive (T2-T4a), node-negative (N0) urothelial transitional cell cancer (TCC) of the bladder

• Focal squamous and/or adenocarcinoma differentiation, defined as ≤ 10% of tumor volume allowed

• The following diagnoses are not allowed:

• Small cell carcinoma

• Sarcomatoid components

• Disease diagnosed with an initial transurethral resection of bladder tumor (TURBT) and a second TURBT performed within 8 weeks of first with attempt to remove all tumor present

• Residual disease after second TURBT allowed

• No more than 14-56 days after second TURBT

• No metastatic disease by chest x-ray and CT scan or MRI of the abdomen and pelvis

• Fresh tumor tissue, paraffin tumor tissue, unstained slides, or cell block specimen from one or both TURBTs available

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• White blood cell count (WBC) at least 3,500/mm^3

• Absolute granulocyte count at least 1,500/mm^3

• Platelet count at least lower limit of normal

Hepatic

• Bilirubin no greater than 1.5 mg/dL

• Aspartate aminotransferase (SGOT) no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL AND/OR

• Creatinine clearance at least 60 mL/min

Other

• No prohibitive medical risk that would preclude radical cystectomy

• No other serious concurrent systemic disorder that would preclude study compliance

• No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer in complete remission, or any other cancer for which patient has been disease-free for 5 years

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior intravesical immunotherapy allowed

Chemotherapy

• No prior systemic chemotherapy for TCC of the urothelium

• Prior intravesical chemotherapy allowed

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for TCC of the urothelium

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Center at Providence Alaska Medical Center	Anchorage	Alaska	United States	99519-6604
2	Banner Thunderbird Medical Center	Glendale	Arizona	United States	85306
3	Banner Desert Medical Center	Mesa	Arizona	United States	85202
4	Banner Baywood Medical Center	Mesa	Arizona	United States	85206
5	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
6	CCOP - Western Regional, Arizona	Phoenix	Arizona	United States	85006
7	Providence Saint Joseph Medical Center - Burbank	Burbank	California	United States	91505
8	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
9	University of California Davis Cancer Center	Sacramento	California	United States	95817
10	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
11	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
12	Shaw Cancer Center at Vail Valley Medical Center	Edwards	Colorado	United States	81632
13	North Colorado Medical Center	Greeley	Colorado	United States	80631
14	McKee Medical Center	Loveland	Colorado	United States	80539
15	Montrose Memorial Hospital Cancer Center	Montrose	Colorado	United States	81401
16	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
17	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
18	Good Samaritan Regional Health Center	Mt. Vernon	Illinois	United States	62864
19	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
20	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
21	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
22	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
23	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
24	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
25	Southwest Medical Center	Liberal	Kansas	United States	67901
26	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
27	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
28	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
29	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
30	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
31	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
32	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67203
33	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
34	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
35	CCOP - Wichita	Wichita	Kansas	United States	67214
36	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
37	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
38	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
39	Christus Schumpert Cancer Treatment Center	Shreveport	Louisiana	United States	71101
40	Cancer Research Center at Boston Medical Center	Boston	Massachusetts	United States	02118
41	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
42	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
43	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
44	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
45	Bay Regional Medical Center	Bay City	Michigan	United States	48708
46	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
47	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
48	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
49	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
50	Hurley Medical Center	Flint	Michigan	United States	48503
51	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
52	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
53	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan	United States	49503
54	Metropolitan Hospital	Grand Rapids	Michigan	United States	49506
55	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
56	Holland Community Hospital	Holland	Michigan	United States	49423
57	Foote Hospital	Jackson	Michigan	United States	49201
58	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48909
59	Hackley Hospital	Muskegon	Michigan	United States	49443
60	Seton Cancer Institute - Saginaw	Saginaw	Michigan	United States	48601
61	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan	United States	48075
62	Munson Medical Center	Traverse City	Michigan	United States	49684
63	St. John Macomb Hospital	Warren	Michigan	United States	48093
64	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
65	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63701
66	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri	United States	63701
67	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
68	CCOP - St. Louis-Cape Girardeau	St. Louis	Missouri	United States	63141
69	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
70	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
71	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
72	St. Vincent Healthcare	Billings	Montana	United States	59101
73	Deaconess Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
74	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
75	St. James Community Hospital	Butte	Montana	United States	59701
76	Big Sky Oncology	Great Falls	Montana	United States	59405
77	Sletten Regional Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
78		Great Falls	Montana	United States	59405
79	St. Peter's Hospital	Helena	Montana	United States	59601
80	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
81	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
82	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
83	Community Medical Center	Missoula	Montana	United States	59801
84	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
85	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
86	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
87	Adirondack Cancer Care - Glens Falls	Glens Falls	New York	United States	12801
88	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
89	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
90	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
91	Wilson Medical Center	Wilson	North Carolina	United States	27893-3428
92	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
93	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
94	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
95	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon	United States	97210
96	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
97	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
98	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
99	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon	United States	97227
100	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
101	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
102	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
103	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
104	University of Tennessee Cancer Institute - Medical Center	Memphis	Tennessee	United States	38104
105	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
106	American Fork Hospital	American Fork	Utah	United States	84003
107	Logan Regional Hospital	Logan	Utah	United States	84321
108	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
109	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
110	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
111	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
112	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
113	Latter Day Saints Hospital	Salt Lake City	Utah	United States	84143
114	Danville Regional Medical Center	Danville	Virginia	United States	24541
115	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
116	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
117	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington	United States	98273
118	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
119	Harborview Medical Center	Seattle	Washington	United States	98104
120	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
121	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
122	Polyclinic First Hill	Seattle	Washington	United States	98122
123	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
124	North Puget Oncology at United General Hospital	Sedro-Wooley	Washington	United States	98284
125	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
126	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
127	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
128	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Primo N. Lara, MD, University of California, Davis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00045630
• Other Study ID Numbers: CDR0000256921; S0219; U10CA032102; NCT00191217
• First Posted: Jan 27, 2003
• Last Update Posted: May 27, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Southwest Oncology Group: anterior urethral cancer; localized transitional cell cancer of the renal pelvis and ureter; posterior urethral cancer; stage II bladder cancer; stage III bladder cancer; transitional cell carcinoma of the bladder; urethral cancer associated with invasive bladder cancer; regional transitional cell cancer of the renal pelvis and ureter
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Urethral Neoplasms; Carcinoma, Transitional Cell; Kidney Neoplasms; Ureteral Neoplasms; Gemcitabine; Paclitaxel; Carboplatin

Study Results

Participant Flow

Arm/Group Title	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
Arm/Group Description	Patients receive 3 cycles (1 cycle = 21 days) of neoadjuvant chemotherapy (800 mg/m^2 of gemcitabine IV and 80 mg/m^2 of Paclitaxel IV on days 1 and 8 and Carboplatin IV on day 1), TURBT within 4-8 weeks of chemotherapy, option of proceeding with immediate cystectomy or observation.
Period Title: Overall Study
STARTED	77
Eligible	75
Eligible and Began Protocol Therapy	74
COMPLETED	71
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
Arm/Group Description	Patients receive 3 cycles (1 cycle = 21 days) of neoadjuvant chemotherapy (800 mg/m^2 of gemcitabine IV and 80 mg/m^2 of Paclitaxel IV on days 1 and 8 and Carboplatin IV on day 1), TURBT within 4-8 weeks of chemotherapy, option of proceeding with immediate cystectomy or observation.
Overall Participants	74
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	18 24.3%
Male	56 75.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.1%
Not Hispanic or Latino	55 74.3%
Unknown or Not Reported	16 21.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.4%
Asian	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.7%
White	70 94.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Performance Status (participants) [Number]
0	50 67.6%
1	16 21.6%
Missing	8 10.8%
Clinical T Stage (participants) [Number]
T2	52 70.3%
T3	17 23%
T4a	5 6.8%
Prior Intravesical Therapy (participants) [Number]
Yes	11 14.9%
No	59 79.7%
Missing	4 5.4%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy
Description	Pathologic complete response (CR) is defined as absence of viable tumor in the TURBT specimen. Stable/No Response is defined as at least some disease evaluation tests were done (same tests as baseline) and status does not qualify for CR or Progression. Progression is defined as one or more of the following must occur: unequivocal progression of disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without documented progression or symptomatic deterioration.
Time Frame	up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis

Arm/Group Title	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
Arm/Group Description	Patients receive 3 cycles (1 cycle = 21 days) of neoadjuvant chemotherapy (800 mg/m^2 of gemcitabine IV and 80 mg/m^2 of Paclitaxel IV on days 1 and 8 and Carboplatin IV on day 1), TURBT within 4-8 weeks of chemotherapy, option of proceeding with immediate cystectomy or observation.
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	46 62.2%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined from the date of registration to date of death from any cause
Time Frame	0-2 years

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in the analysis

Arm/Group Title	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
Arm/Group Description	Patients receive 3 cycles (1 cycle = 21 days) of neoadjuvant chemotherapy (800 mg/m^2 of gemcitabine IV and 80 mg/m^2 of Paclitaxel IV on days 1 and 8 and Carboplatin IV on day 1), TURBT within 4-8 weeks of chemotherapy, option of proceeding with immediate cystectomy or observation.
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	59 79.7%

3. Secondary Outcome

Title	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Description	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time Frame	Patients were assessed for adverse events at weeks 1, 2, 4, 5, 7, 8, and following surgery

Outcome Measure Data

Analysis Population Description

Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.

Arm/Group Title	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
Arm/Group Description	Patients receive 3 cycles (1 cycle = 21 days) of neoadjuvant chemotherapy (800 mg/m^2 of gemcitabine IV and 80 mg/m^2 of Paclitaxel IV on days 1 and 8 and Carboplatin IV on day 1), TURBT within 4-8 weeks of chemotherapy, option of proceeding with immediate cystectomy or observation.
Measure Participants	74
Abnormal troponin I (cTnI)	1 1.4%
Allergic reaction	2 2.7%
Anemia	5 6.8%
Bilirubin increase	1 1.4%
Cardiac ischemia/infarction	1 1.4%
Creatinine increase	1 1.4%
Diarrhea without colostomy	2 2.7%
Duodenal ulcer	1 1.4%
Dyspnea	1 1.4%
Fatigue/malaise/lethargy	3 4.1%
Febrile neutropenia	2 2.7%
GI-other	1 1.4%
Hemolysis	1 1.4%
Incontinence	1 1.4%
Infection with 3-4 neutropenia	2 2.7%
Infection, unk ANC	2 2.7%
Leukopenia	22 29.7%
Lymphopenia	1 1.4%
Melena/ GI bleeding	1 1.4%
Neutropenia/granulocytopenia	41 55.4%
SGPT (ALT) increase	1 1.4%
Thrombocytopenia	13 17.6%
Ureteral obstruction	1 1.4%
Urinary tr infect w/ neutrop	1 1.4%
Urinary tr infect w/o neutrop	1 1.4%
Vomiting	1 1.4%

Adverse Events

Time Frame	Patients were assessed for adverse events at weeks 1, 2, 4, 5, 7, 8, and following surgery
Arm/Group Title	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
Arm/Group Description	Patients receive 3 cycles (1 cycle = 21 days) of neoadjuvant chemotherapy (800 mg/m^2 of gemcitabine IV and 80 mg/m^2 of Paclitaxel IV on days 1 and 8 and Carboplatin IV on day 1), TURBT within 4-8 weeks of chemotherapy, option of proceeding with immediate cystectomy or observation.
All Cause Mortality
	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
	Affected / at Risk (%)	# Events
Total	2/74 (2.7%)
Gastrointestinal disorders
GI-other	1/74 (1.4%)
Infections and infestations
Infection with 3-4 neutropenia	1/74 (1.4%)
Other (Not Including Serious) Adverse Events
	Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery
	Affected / at Risk (%)	# Events
Total	73/74 (98.6%)
Blood and lymphatic system disorders
Anemia	49/74 (66.2%)
Eye disorders
Blurred vision	5/74 (6.8%)
Gastrointestinal disorders
Abdominal pain/cramping	8/74 (10.8%)
Constipation/bowel obstruction	21/74 (28.4%)
Diarrhea without colostomy	18/74 (24.3%)
Nausea	31/74 (41.9%)
Stomatitis/pharyngitis	8/74 (10.8%)
Vomiting	9/74 (12.2%)
General disorders
Edema	7/74 (9.5%)
Fatigue/malaise/lethargy	61/74 (82.4%)
Fever without neutropenia	8/74 (10.8%)
Pain-other	14/74 (18.9%)
Rigors/chills	9/74 (12.2%)
Immune system disorders
Allergic reaction	6/74 (8.1%)
Infections and infestations
Infection w/o 3-4 neutropenia	6/74 (8.1%)
Infection, unk ANC	4/74 (5.4%)
Urinary tr infect w/o neutrop	6/74 (8.1%)
Investigations
Creatinine increase	7/74 (9.5%)
Leukopenia	48/74 (64.9%)
Lymphopenia	6/74 (8.1%)
Neutropenia/granulocytopenia	54/74 (73%)
SGOT (AST) increase	11/74 (14.9%)
SGPT (ALT) increase	15/74 (20.3%)
Thrombocytopenia	41/74 (55.4%)
Weight loss	8/74 (10.8%)
Metabolism and nutrition disorders
Anorexia	18/74 (24.3%)
Dehydration	4/74 (5.4%)
Hyperglycemia	15/74 (20.3%)
Hypoalbuminemia	5/74 (6.8%)
Hyponatremia	5/74 (6.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/74 (9.5%)
Bone pain	5/74 (6.8%)
Myalgia	8/74 (10.8%)
Nervous system disorders
Dizziness/light headedness	5/74 (6.8%)
Headache	6/74 (8.1%)
Sensory neuropathy	7/74 (9.5%)
Psychiatric disorders
Insomnia	4/74 (5.4%)
Renal and urinary disorders
Dysuria	4/74 (5.4%)
Hematuria	4/74 (5.4%)
Urinary frequency/urgency	11/74 (14.9%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	6/74 (8.1%)
Skin and subcutaneous tissue disorders
Alopecia	36/74 (48.6%)
Pruritus	5/74 (6.8%)
Rash/desquamation	9/74 (12.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.