Combination Chemotherapy in Treating Patients With Transitional Cell Cancer of the Urothelium

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. It is not yet known which combination chemotherapy regimen is most effective for transitional cell cancer of the urothelium. PURPOSE: Randomized phase II/III trial to compare different combination chemotherapy regimens in treating patients who have transitional cell cancer of the urothelium.

Sex

All

Minimum age

18 Years

DISEASE CHARACTERISTICS:

* Histologically confirmed transitional cell cancer of the urothelium, including the renal pelvis, ureters, urinary bladder, and urethra, meeting 1 of the following criteria:

  * Unresected positive lymph node
  * Distant metastases (M1, stage IV)
  * Unresectable primary bladder cancer (T3-4)
* Measurable disease
* Ineligible for cisplatin-based chemotherapy and presenting with the following:

  * WHO performance status 2 AND/OR
  * Glomerular filtration rate greater than 30 mL/min but less than 60 mL/min
* No brain metastases or other CNS lesions

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* See Disease Characteristics

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 4,000/mm\^3
* Platelet count at least 125,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.25 times normal
* AST/ALT no greater than 3 times normal (5 times normal if liver metastases are present)

Renal:

* See Disease Characteristics
* Calcium normal

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception during and for 6 months after study participation
* No psychological, familial, sociological, or geographical condition that would preclude study participation
* No other prior or concurrent malignancy except cured basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior systemic biologic therapy

Chemotherapy:

* See Disease Characteristics
* No prior systemic cytotoxic therapy (including adjuvant and neoadjuvant chemotherapy)

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 3 months since prior radiotherapy
* Prior radiotherapy to study lesions allowed if there is evidence of disease progression

Surgery:

* Not specified

• RESULTDe Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Gil T, Marreaud S, Daugaard G, Skoneczna I, Collette S, Lorent J, de Wit R, Sylvester R. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol. 2012 Jan 10;30(2):191-9. doi: 10.1200/JCO.2011.37.3571. Epub 2011 Dec 12. PMID 22162575
• RESULTDe Santis M, Bellmunt J, Mead G, Kerst JM, Leahy M, Maroto P, Skoneczna I, Marreaud S, de Wit R, Sylvester R. Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer "unfit" for cisplatin-based chemotherapy: phase II--results of EORTC study 30986. J Clin Oncol. 2009 Nov 20;27(33):5634-9. doi: 10.1200/JCO.2008.21.4924. Epub 2009 Sep 28. PMID 19786668
• RESULTDe Santis M, Bellmunt J, Mead B, et al.: Randomized phase II/III study assessing gemcitabine/carboplatin (GC) and methotrexate/carboplatin/vinblastine (M-CAVI) in previously untreated patients (pts) with advanced urothelial cancer ineligible for cisplatin based chemotherapy: phase II results of. [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-288, 2008.