Pemetrexed Disodium and Gemcitabine in Treating Patients With Advanced Cancer of the Urothelium

OBJECTIVES:

Primary

• Determine the response rate in patients with previously untreated advanced cancer of the urothelium treated with pemetrexed disodium and gemcitabine.
• Determine the toxicity of this regimen in these patients.

Secondary

• Determine the overall survival and time to progression in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Patients also receive cyanocobalamin intramuscularly once every 9 weeks and folic acid orally once daily beginning on day -6 and continuing until 3 weeks after the completion of study therapy. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 24-46 patients will be accrued for this study within 15 -18 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed cancer of the urothelium (renal pelvis, ureter, bladder, or urethra)

• Any of the following types:

• Transitional cell carcinoma (TCC)
• Mixed histologies containing a component of TCC
• Non-TCC of the urothelium (renal pelvis, ureter, bladder, or urethra)
• Progressing regional or metastatic disease
• Measurable disease
• No clinical evidence of CNS metastases
• No evidence of clinically significant (by physical exam or plain film) third-space fluid collections (pleural effusions or ascites)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• AST no greater than 3 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN

Renal

• Creatinine clearance at least 45 mL/min

Cardiovascular

• No history of severe cardiovascular disease (i.e., American Heart Association class III or IV heart disease)
• No uncontrolled congestive heart failure
• No ventricular dysrhythmias

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No active unresolved infection
• No other prior malignancy unless curatively treated and disease free for an appropriate (disease-specific) period of time
• Able and willing to receive folic acid and cyanocobalamin supplementation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior systemic biologic response modifier therapy

Chemotherapy

• No prior systemic chemotherapy for metastatic disease
• More than 1 year since prior neoadjuvant or adjuvant chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No prior pelvic radiotherapy
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior major surgery and recovered

Other

• More than 7 days since prior parenteral antibiotics
• No salicylates for 2 days before, during, and for 2 days after administration of pemetrexed disodium
• No nonsteroidal anti-inflammatory drugs for at least 5 days before, during, and for 2 days after administration of pemetrexed disodium