A Phase II Study of PS-341 in Advanced or Metastatic Urothelial Cancer (Transitional Cell Cancer of the Bladder, Ureter, and Renal Pelvis)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed transitional cell cancer of the urothelium,
including the bladder, renal pelvis, or ureter

- Advanced or metastatic disease

- At least 1 unidimensionally measurable lesion

- At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

- The following are not considered measurable disease:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- No known brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1 OR

- Karnofsky 80-100%

Life expectancy

- More than 3 months

Hematopoietic

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic

- Bilirubin no greater than 1.25 times upper limit of normal (ULN)

- AST/ALT no greater than 3 times ULN (less than 5 times ULN if liver metastases are
present)

Renal

- Creatinine no greater than 1.5 times ULN OR

- Creatinine clearance at least 45 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able and willing to undergo biopsy of tumor lesions

- No other primary cancer requiring treatment within the past 3 years except curatively
treated nonmelanoma skin cancer or carcinoma in situ of the cervix

- No grade 1 or greater peripheral neuropathy

- No ongoing or active infection

- No other concurrent uncontrolled illness

- No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No more than 2 prior chemotherapy regimen for metastatic disease

- Prior neoadjuvant or adjuvant therapy allowed provided it was completed more
than 12 months prior to study entry

- Patients who relapse within 12 months after completion of neoadjuvant or
adjuvant therapy are allowed provided they did not receive chemotherapy for
recurrent disease

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- Prior chemotherapy as a radiosensitizer is allowed* NOTE: *May be administered
concurrently with radiotherapy; may be in addition to a single line of therapy for
locally advanced or metastatic disease

Endocrine therapy

- Not specified

Radiotherapy

- See Chemotherapy

- More than 4 weeks since prior myelotoxic radiotherapy (more than 3,000 cGy to fields
including substantial bone marrow) and recovered

- No concurrent radiotherapy

Surgery

- At least 4 weeks since prior surgery for cancer of the urothelium (except nephrostomy
tubes and ureteral stents)

Other

- At least 4 weeks since any prior therapy and recovered

- No other concurrent investigational or commercial agents or therapies intended to
treat the malignancy

- No concurrent combination antiretroviral therapy for HIV-positive patients