Phase II study of gemcitabine, 5-fluorouracil, and leucovorin in patients with pancreatic cancer.

The primary goal of this phase II study was to determine the efficacy of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil in patients with pancreatic cancer. Eligibility criteria included nonresectable locally advanced or metastatic pancreatic adenocarcinoma and measurable disease. Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every 4 weeks. Twenty nine patients were enrolled. The overall response rate was 21% (95% confidence interval: 8% to 40%), consisting of one complete response and five partial responses; 16 patients (55%) had stable disease. Median survival was 8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was generally of short duration. No thrombocytopenia or evidence of cumulative myelosuppression was observed. The only significant nonhematologic events were grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is active and well tolerated compared with results reported for each of these single agents. Thus, this combination justifies future comparative clinical trials. Semin Oncol 28 (suppl 10):44-49.

Phase II of doxorubicin/taxol in metastatic breast cancer. Argentine Multicenter Taxol Group.

PURPOSE: To assess the response rate, survival, and toxicity of Taxol (paclitaxel) as 1-h infusion plus doxorubicin as first-line treatment for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Seventy-six patients with untreated MBC were recruited. All of them had measurable disease and were evaluable for toxicity. Fifty-five percent of the patients had visceral involvement. The dose of doxorubicin was fixed at 50 mg/m2 as a short intravenous infusion, followed by 200 mg/m2 of Taxol as a 1-h intravenous infusion. Doxorubicin was administered during the first seven cycles, continuing with Taxol only up to a maximum of ten cycles. RESULTS: Neutropenia was the most important toxicity: 30% grade 3 and 18% grade 4. Only 2 patients showed a decrease in the left ventricular ejection fraction (LVEF) which caused discontinuing the treatment. No clinical congestive heart failure (CHF) was observed. Seventy-four patients were eligible for response evaluation: 10 (14%) achieved complete response (CR) and 46 (62%) achieved partial response (PR). The mean duration of response was 13.47+/-1.35 months (95% confidence interval (CI): 10.82; 16.12) and the mean survival was 21.50+/-1.42 months (95% CI: 18.72; 24.29). CONCLUSION: The overall response (OR) rate was 76%. No CHF was assessed and 2 patients stopped treatment due to LVEF decrease. Although doxorubicin 50 mg/m2 followed by Taxol 200 mg/m2 in 1-h intravenous infusion presents a toxicity profile which demands a close follow-up, it represents a convenient outpatient schedule with similar activity rate compared to longer Taxol infusions.

Uracil/tegafur plus oral calcium folinate in advanced breast cancer.

Uracil and tegafur (in a molar ratio of 4:1 [UFT]) has proven activity against breast cancer and is delivered in an easy-to-administer oral formulation. Orzel, which combines UFT with the oral biomodulator, calcium folinate, may provide even greater antitumor efficacy against breast cancer. Here, we describe the preliminary results of this phase II trial investigating the feasibility of 250 mg/m2/day of UFT plus 45 mg/day of oral calcium folinate administered to highly pretreated patients with advanced breast cancer. The results indicate a highly tolerable regimen and an overall response rate of 27.8% in a group of poor-prognosis patients. These findings warrant continued investigation.

Paclitaxel in platinum-resistant ovarian cancer patients. Argentine Multicenter Taxol Group.

Paclitaxel (Taxol; Bristol-Myers Squibb Company; Princeton, NJ) is an antineoplastic agent that inhibits microtubular function and has shown efficacy in several solid tumors, mainly ovarian tumors, in which 20% to 40% response rates in previously treated patients were observed. We conducted a study to assess survival, response rate, and toxicity associated with paclitaxel treatment in patients with advanced ovarian cancer resistant to platinum therapy. Between September 1994 and November 1996, 38 patients were admitted for study and 37 were evaluable. All had disease progression or relapse within 1 year of receiving platinum-containing first-line chemotherapy. Mean age was 59 years (range, 30 to 75 years), all had bulky disease, and 18 showed increased carbohydrate antigen-125 at admission. They were treated every 3 weeks with paclitaxel 175 mg/m2 as a 3-hour infusion, preceded by standard premedication. Response rate was 51.3%, with a median response duration of 10.0 months and a median survival rate of 16.8 months. Mild to moderate hematologic toxicity was observed with only one episode of grade 4 neutropenia, without fever. Gastrointestinal toxicity was moderate and peripheral neuropathy was mild, except for two patients who had concomitant pathologies or previous treatment, which might have caused some neuropathy. We concluded that paclitaxel given as a 3-hour infusion was easily administered for ambulatory treatment, with mild to moderate toxicity and promising results based on rate and duration of response as well as survival.

Sequential versus alternating regimens in the treatment of advanced breast cancer. Argentine Breast Cancer Cooperative Group.

With the object of proving whether sequential or alternate forms of chemotherapy would be advantageous one over the other in treating advanced breast cancer and with the purpose of evaluating two different anthracyclines at equimolecular doses in the above-mentioned alternating regimens, 250 patients who had received no prior chemo- or hormonotherapy were entered in a prospective randomized trial. Group A was administered 4-epiadriamycin and cyclophosphamide for 8 courses, followed by 6 cycles of CMF, and medroxyprogesterone acetate (MPA) from the beginning of therapy until progression. In group B, adriamycin + cyclophosphamide were alternated with CMF every two courses until 14 cycles were completed. Group C received 4'-epiadriamycin + cyclophosphamide alternated with CMF for 14 courses. In groups B and C, MPA was administered as in group A. Two hundred and twenty-four patients were evaluated. CR + PR were observed in 55.8% of group A, 43.4% of group B, and 46.4% of group C. Median duration of responses was 16 months (m) in group A, 13 m in group B and 20 m in group C, and median survival (CR + PR) was 16.5 m in group A, 16 m in group B and 24 m in group C. There were no statistically significant differences among the three groups in terms of response rate, duration of response and survival; furthermore, toxicity was moderate in all groups. At equimolecular doses there were no differences between adriamycin and epirubicin in the alternating schedules.

[Treatment of advanced digestive cancer with fluorouracil and methyl-CCNU]. / Tratamiento del cáncer digestivo avanzado con fluoracilo y metil - CCNU.

We relate the experience obtained by treatment of 20 advanced digestive cancer patients, with the association of 5 fluorouracil and methyl-C.C.N.U. Objective response was found in 4 patients (20%). Toxicity consisted of leucopenia in 3 patients, allergic phenomena in 2 and diarrhea in 1 patient. Mean survival is increased in 3 months in responders, when compared with non-responders, although this difference has not statistical value.

Tratamiento del cáncer digestivo avanzado con fluoracilo y metil - CCNU. / [Treatment of advanced digestive cancer with fluorouracil and methyl-CCNU]

We relate the experience obtained by treatment of 20 advanced digestive cancer patients, with the association of 5 fluorouracil and methyl-C.C.N.U. Objective response was found in 4 patients (20

). Toxicity consisted of leucopenia in 3 patients, allergic phenomena in 2 and diarrhea in 1 patient. Mean survival is increased in 3 months in responders, when compared with non-responders, although this difference has not statistical value.

Tratamiento del cáncer digestivo avanzado con fluoracilo y metil - CCNU / [Treatment of advanced digestive cancer with fluorouracil and methyl-CCNU]

We relate the experience obtained by treatment of 20 advanced digestive cancer patients, with the association of 5 fluorouracil and methyl-C.C.N.U. Objective response was found in 4 patients (20

). Toxicity consisted of leucopenia in 3 patients, allergic phenomena in 2 and diarrhea in 1 patient. Mean survival is increased in 3 months in responders, when compared with non-responders, although this difference has not statistical value.