Paclitaxel, cisplatin and methotrexate combination chemotherapy is active in the treatment of refractory urothelial malignancies.

PURPOSE: We investigated the activity of combination chemotherapy consisting of paclitaxel, cisplatin and methotrexate in patients with advanced urothelial cancers. MATERIALS AND METHODS: A total of 25 consecutive patients with metastatic refractory urothelial malignancies was treated with a combination of 200 mg./m.2 paclitaxel, 30 mg./m.2 methotrexate and 70 mg./m.2 cisplatin in a pilot study. RESULTS: There were no complete responses. Of 25 patients 10 (40%), including 3 of 7 with liver metastases, had a partial response. Hematological and nonhematological toxicity was tolerable. CONCLUSIONS: The combination chemotherapeutic regimen of paclitaxel, cisplatin and methotrexate is active in patients with advanced urothelial cancer and warrants further study.

SMS 201-995 in the treatment of refractory prostatic carcinoma.

The long-acting synthetic somatostatin analog, SMA 201-995, was used to treat patients with advanced hormonal-refractory prostate cancer. Twenty-two of 24 study patients treated are evaluable for toxicity and 20 are evaluable for response. The dose of SMS 201-995 was 100 mg subcutaneously every 8 hours for 6 weeks. Two patients suffered intolerable gastrointestinal complications requiring early cessation of therapy. No patient had objective evidence of tumor regression. After developing a clinical suspicion that tumor growth accelerated with SMS 201-995, we observed 10 patients closely for 2 months before beginning SMS 201-995 treatment and for the first 2 months on the therapy. In these 10 patients, the serum prostatic acid phosphatase level rose at an accelerated rate after 1 to 2 months of treatment. Among the 20 patients treated and evaluable for response, new osseous metastases developed in 12 and new visceral metastases in 4; 1 developed disseminated intravascular coagulation and 2 developed neurologic complications (mean time to objective progression, 5.6 weeks). Six patients received salvage chemotherapy after disease progressed on SMS 201-995 therapy, 5 of whom have achieved objective tumor regressions. We believe SMS 201995 stimulates prostatic tumor growth and may sensitize tumor cells to subsequent chemotherapy.

5-Fluorouracil and interferon-alpha in chemotherapy refractory bladder carcinoma: an effective regimen.

Seventy-seven patients with metastatic transitional cell carcinoma of the bladder who were unable to receive primary Cisplatin-based therapy or failed primary chemotherapy received one of three sequential 5-Fluorouracil-based salvage regimens: a) 5-Fluorouracil (1000 mg/m2 B.S.A. x 5 days) and Mitomycin-C (14 mg/m2 B.S.A. 6 week intervals), b) 5-Fluorouracil (750 mg/m2 B.S.A. x 5 days) and a-Interferon (5 miu/m2 B.S.A. daily x 5 then 3 times a week (TIW), c) 5-Fluorouracil (500 mg/m2 B.S.A. x 5 days), a-Interferon (5 miu/m2 B.S.A. x 5 days then TIW) and 13-Cis Retinoic Acid in escalating doses daily. Only 1 (6%) of the patients with regimen A responded, whereas 9 (30%) of the patients with regimen B and 8 (27%) in regimen C responded. Although all responses were partial remissions, responses were seen in patients with advanced and initially refractory transitional cell carcinomas. This data reveals that a-Interferon and 5-Fluorouracil is an effective combination in the treatment of metastatic transitional cell carcinoma and worthy of further study.

Carcinoma of the bladder.

Over the past 20 years, advances in tumor staging, tumor biology, and therapeutic management have positively influenced both cure rates and overall survival of patients with bladder cancer. Treatment recommendations depend on the stage of the disease, the grade of tumor, likelihood of recurrence, and the patient's medical condition. These patients continue to be faced with treatment options that affect their physical, sexual, and psychosocial well-being.

Fluorouracil and recombinant human interferon alfa-2a in the treatment of metastatic chemotherapy-refractory urothelial tumors.

Thirty patients with advanced metastatic and chemotherapy-refractory urothelial tumors received a combination of fluorouracil (5-FU) and recombinant human interferon alfa-2a. Thirty-six sites of metastases were present in the 30 study patients, and the median Eastern Cooperative Oncology Group performance status was 3 (range, 1 to 4). All patients had failed to respond to primary combined methotrexate/cisplatin-based chemotherapy. Nine (30%; confidence interval, 15% to 47%) of the patients achieved a partial response. The mean duration of response was more than 5.2 months (median, 6 months; range, 3 to 8 months). Two patients who achieved a partial response of 5 and 7 months' duration, respectively, had control of residual disease (one with radiation and one with surgical excision) and have remained disease-free for an additional period of more than 7 and 13 months, respectively. These data suggest that the combination of 5-FU and recombinant human interferon alfa-2a is synergistic, with clinical significance for the treatment of urothelial tumors. The response rate for this combination of drugs is higher than that anticipated for either of these agents used alone. Additional confirmatory trials are needed to evaluate the significance of these findings.

Complete responses in metastatic transitional cell carcinoma of the prostate with cisplatin regimens.

We describe 3 patients with metastatic transitional cell carcinoma of the prostate who achieved a complete response with regimens containing cisplatin. Two patients received cyclophosphamide and weekly cisplatin, and 1 was given cyclophosphamide, doxorubicin and cisplatin. All 3 patients had extensive pulmonary metastasis at initiation of chemotherapy. One patient, who also had massive local disease, suffered an isolated brain metastasis 9 months after completion of chemotherapy but he remains in systemic remission 5 months later. Another patient had bilateral brain metastases 3 months after achieving complete remission with chemotherapy, followed 4 months later by systemic relapse. The third patient, who also had bone and bone marrow metastasis, is free of disease 20 months after completion of chemotherapy. In contrast, none of 14 patients with transitional cell carcinoma of the bladder and other sites treated with the same regimens obtained a complete response. Advanced transitional cell carcinoma of the prostate must be recognized promptly, since it is nonresponsive to hormonal manipulation and complete responses have been achieved with cisplatin chemotherapy programs as used in our patients.

Carcinoembryonic antigen and beta-human chorionic gonadotropin as serum markers for advanced urothelial malignancies.

Serum levels of carcinoembryonic antigen and beta-subunit of human chorionic gonadotropin were measured in 92 patients with advanced urothelial malignancies referred to us for chemotherapy. Elevations of carcinoembryonic antigen and/or beta-human chorionic gonadotropin occurred in 60 of the 92 patients (65 per cent). Minimal elevations (less than 50 per cent above the normal range) occurred in 25 patients (27 per cent), while 35 (38 per cent) had significant elevations (more than 50 per cent above the normal range). Of the latter patients carcinoembryonic antigen alone was elevated in 16 (17 per cent), beta-human chorionic gonadotropin alone in 13 (14 per cent) and both in 6 (6 per cent). Among the 24 patients with initially elevated levels whose markers were re-evaluated during therapy the marker levels correlated with disease course in all 15 whose elevations were more than 50 per cent and in 4 of 9 with minimal elevations. In patients with adenocarcinoma of the bladder the carcinoembryonic antigen level frequently was elevated (9 of 10). We conclude that serum levels of carcinoembryonic antigen or beta-human chorionic gonadotropin are significantly elevated (more than 50 per cent above the normal range) in 38 per cent of the patients with advanced urothelial malignancies and can be used as tumor markers, since they correlate with the clinical course of the patient and the response to therapy. Serum carcinoembryonic antigen levels usually are elevated in patients with bladder adenocarcinoma.

Continuous infusion of vinblastine for advanced hormone-refractory prostate cancer.

Thirty-nine patients with metastatic prostate cancer refractory to hormonal manipulation were treated with vinblastine by continuous infusion. The dose was 1.5 mg/m2 daily for 5 days. A 21% response rate was obtained. Eight patients, two with visceral metastasis, one with nodal disease, and five with osseous metastasis achieved objective response. The median duration of response was 28 weeks. Myelosuppression was the major side effect: the median leukocyte count nadir was 2.8 X 10(3)/ml and the median platelet count nadir was 184 X 10(3)/ml.