To evaluate the relative efficacy of cisplatin, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (CISCA) versus methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC), a prospective randomized trial was performed in patients with advanced metastatic urothelial tumors. Patients were stratified by histologic disease type and degree of tumor dissemination. Equal distribution of the clinical characteristics was achieved. One hundred ten patients with metastatic disease of the urinary tract (86 bladder, 16 renal pelvis, seven ureter, one prostatic urethra) met eligibility criteria and were enrolled on study. These represented 82% of the total patients seen during the study period in the Section of Genitourinary Oncology who met the eligibility criteria. The combined complete and partial response rate was significantly higher for patients treated with MVAC than for those treated with CISCA (65% v 46%; P less than .05). The survival duration of MVAC-treated patients was significantly longer than that of CISCA-treated patients (mean, 62.6 weeks; median, 48.3; range, 5.0+ to 162.3+ v mean, 40.4 weeks; median, 36.1; range, 7+ to 147.1+). We conclude that MVAC chemotherapy is superior to CISCA chemotherapy, achieving a higher response rate and a longer survival for equivalent patients with metastatic urothelial tumors.

Chemotherapy and androgen ablation followed by radical prostatectomy was feasible in patients with locally advanced prostate cancer. Although the goal of achieving a 20% rate for pT0 status was not achieved, we believe this type of integrated therapeutic strategy should be investigated further for its ability to alter the course of regionally advanced prostate cancer.

No abstract

Cis-platinum-based chemotherapy combinations have improved the outcome of patients with metastatic urothelial tumors, since two-thirds of these patients respond to treatment. Nevertheless, the majority of such patients have relapse within a median of 12 months. To define the pattern of failure and subsequent outcome, we retrospectively assessed 58 consecutive patients with relapse after prior response to cis-platinum-based combination chemotherapy. Of the patients who presented initially with local-regional metastases, 74% had relapse with involvement of a similar site, while only 26% of these patients had visceral metastases at relapse. The median survival after relapse was 9 months, and parameters associated with longer survival were local-regional relapse (10.7 months) and response to salvage chemotherapy (12.6 months). These data suggest that select patients with urothelial tumors and local-regional metastases may benefit from consolidation therapy with surgery or radiotherapy after maximum response to chemotherapy.

Thirty-two assessable patients with metastatic urothelial tumors refractory to standard chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were treated with escalated doses of MVAC plus unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Results of this phase I trial revealed that escalated MVAC (30 mg of methotrexate/m2, 4 mg of vinblastine/m2, 60 mg of doxorubicin/m2, and 100 mg of cisplatin/m2) can be tolerated by heavily pretreated patients. The side effects of rhGM-CSF are dose- and schedule-dependent. The maximum tolerated dose is 250 micrograms/m2 per day as a single dose administered subcutaneously (SC) for 10 consecutive days. This dose is well tolerated in outpatients, resulting in only modest fever and few side effects. The same dose delivered as a continuous infusion or a higher dose delivered either as a continuous infusion or SC caused significant side effects. For phase II trials, the starting dose of rhGM-CSF when combined with escalated MVAC is 120 micrograms/m2 per day SC for 10 consecutive days. forty percent of the treated patients responded, seven (23%) with complete remission and five (17%) with partial remission. This response rate is higher than anticipated from such a modest dosage escalation in chemotherapy-refractory patients.