Phase II trial of toremifene in androgen-independent prostate cancer: a Penn cancer clinical trials group trial.

Toremifene has antiestrogenic and estrogenic properties in vitro and in vivo. In addition, it may have antiangiogenesis and antimicrotubule properties at higher doses. Studies have demonstrated the efficacy of this agent in the treatment of metastatic breast cancer. We performed a phase II trial of toremifene in patients with androgen-independent prostate cancer (AIPC). Patients with an increasing prostate-specific antigen level despite castrate testosterone levels and antiandrogen withdrawal were eligible. Patients could not have received prior salvage hormonal therapy or chemotherapy. Patients received toremifene at 300 mg/m2/d orally (maximum dose 640 mg/d). Fifteen patients were treated. Patients received treatment for a median of 13 weeks (range, 4-30 weeks). The median age was 72 years (range, 58-80 years). The median Eastern Cooperative Oncology Group performance status was 0. The treatment was well tolerated and toxicity was mild. Two patients had grade III hepatic toxicity; one had grade III hyperglycemia. There were no treatment-related deaths. No objective responses were demonstrated. In summary, toremifene is not effective therapy for AIPC at the dose and schedule evaluated in this trial.

A phase II trial of 5-fluorouracil, leucovorin, and interferon alpha 2A (IFN-alpha 2a) in metastatic pancreatic carcinoma: a Penn Cancer Clinical Trials Group (PCCTG) trial.

A phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil (5-FU), leucovorin, and inteferon alpha-2a in metastatic pancreatic carcinoma. Twenty-three patients were entered in this study. Four patients withdrew before receiving treatment and one patient was nonevaluable for response because of treatment-related toxicity. The most common significant toxicity was nausea and vomiting. Treatment-related hospitalization was significant. Of 18 evaluable patients, 4 maintained stable disease and 14 had disease progression. None had an objective clinical response. We conclude that this biochemically modulated 5-FU regimen is ineffective treatment for advanced pancreatic carcinoma, with significant toxicity even in highly selected patients with an ambulatory performance status.

Paclitaxel plus carboplatin in advanced carcinoma of the urothelium: an active and tolerable outpatient regimen.

PURPOSE: To determine the toxicity and efficacy of an outpatient regimen of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium. PATIENTS AND METHODS: Patients received paclitaxel 150 to 225 mg/m2 over 3 hours followed by carboplatin (targeted area under the concentration-time curve [AUC], 6 mg/mL x min) every 3 weeks. During phase I accrual, 16 patients were treated; 17 additional patients were enrolled at the phase II dose. The median age was 70 years (range, 47 to 82). The median serum creatinine concentration was 1.1 mg/dL (range, 0.7 to 2.7) and the median estimated creatinine clearance was 52 mL/min (range, 24 to 110). RESULTS: During phase I accrual, the maximum-tolerated dose (MTD) of the regimen was not defined. Phase II accrual occurred at the paclitaxel 225 mg/m2 dose level. A total of 156 cycles were administered. The median number of cycles received was five (range, one to eight). Sensorimotor neuropathy was the principal nonhematologic toxicity. Significant granulocytopenia was common, but significant thrombocytopenia was not. Objective responses were demonstrated at all dose levels. At the phase II dose (paclitaxel 225 mg/m2 followed by carboplatin at AUC 6 mg/mL x min), the objective response rate was 50% (95% confidence interval [CI], 28% to 72%). CONCLUSION: Paclitaxel plus carboplatin is an active and tolerable outpatient treatment for patients with advanced carcinoma of the urothelium. The ability to administer this combination over multiple cycles even to patients with advanced age and abnormal renal function makes it well suited for this patient population. Confirmatory trials of this regimen are ongoing.

A phase II study of 5-fluorouracil, leucovorin, adriamycin, and cisplatin (FLAP) for metastatic gastric and gastroesophageal junction adenocarcinoma. A Penn Cancer Clinical Trial Group and Roswell Park Cancer Institute Community Oncology Research Program Trial.

A Phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil, leucovorin, Adriamycin, and cisplatin combination chemotherapy (FLAP) in patients with previously untreated advanced gastric and gastroesophageal (GE) junction adenocarcinoma. Forty-two consecutive patients were enrolled to received FLAP in this multi-institutional trial. Response, toxicity, and survival data were noted. Fifteen of 42 (36%) patients demonstrated objective responses, with two complete responses (5%) and 13 partial responses (31%). The median time to disease progression was 17 weeks, and the overall survival duration was 30 weeks. Myelosuppression was significant, requiring dose modifications, but there were no treatment-related deaths. FLAP is an active regimen in the treatment of advanced gastric and GE junction adenocarcinoma. We are presently using this regimen in the neoadjuvant setting in patients with gastric and GE junction cancers.

Phase I trial of paclitaxel/carboplatin in advanced carcinoma of the urothelium.

We performed a phase I trial of 3-hour paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (dose levels of 150, 175, 200, and 225 mg/m2) plus carboplatin dosed to an area under the concentration-time curve of 6. Sixteen patients were treated. Dose-limiting neuropathy was demonstrated in one patient each at the 175 and 200 mg/m2 dose levels. Grade 3 to 4 granulocytopenia was common; grade 3 to 4 thrombocytopenia was uncommon. The maximum tolerated dose of the regimen was not reached. Two complete and seven partial responses were demonstrated. We conclude that paclitaxel 225 mg/m2 plus carboplatin dosed to an area under the concentration-time curve of 6 can be administered to patients with advanced carcinoma of the urothelium. The regimen has encouraging preliminary activity. Phase II accrual is ongoing.

A pilot trial of 5-FU, leucovorin, and cisplatin with or without adriamycin in advanced cancer.

In a pilot trial, we treated patients with solid tumors with 5-FU (5-fluorouracil), leucovorin (LV), and cisplatin (FLP) with Adriamycin in selected patients (FLAP). 5-FU/LV were administered weekly for 6 weeks, with cisplatin at two dose levels (and Adriamycin in some patients) at weeks 1 and 4. Nine patients received FLP; 11 received FLAP.FLP was able to be administered with a cisplatin dose of 75 mg/m2; the maximum-tolerated dose of FLAP included a cisplatin dose of 60 mg/m2. Significant toxicities included granulocytopenia, thrombocytopenia, and diarrhea. Preliminary activity was demonstrated with FLAP in patients with adenocarcinomas of the stomach and gastroesophageal (GE) junction. Ongoing trials of FLAP are underway in patients with gastric and GE junction carcinomas in the neoadjuvant and advanced disease settings.