Lopez M

PACLITAXEL ACTIVITY IN ANTHRACYCLINE REFRACTORY BREAST CANCER PATIENTS

Aims and background We investigated the efficacy and tolerability of two doses of paclitaxel, 175 mg/m2 and 135 mg/m2, over a 3-hr infusion, without prophylactic G-CSF, in heavily pretreated patients with anthracycline-resistant breast cancer. Although paclitaxel may share with anthracyclines a common mechanism of drug resistance, there is evidence that the two drugs are not completely cross resistant. Methods From July 1994 to January 1996, 42 patients were treated every 3 weeks, for a maximum of 6 cycles; paclitaxel dose was established according to pretreatment extension. Results In 41 assessable patients we observed 9 partial responses, for an overall response rate of 22% (95% CI, 10–34%). There was no difference in response rate between the two dose levels. Median duration of response was 9 months, median time to progression 5 months, and median survival 9 months. The dose-limiting toxicity was neutropenia, which was grade 3–4 in 40% (135 mg/m2) and 62% (175 mg/m2) of the patients (P = 0.28); neutropenic fever occurred in 24% of the patients, without significant differences between the two dose levels. Other toxicity was mild to moderate. Conclusions Paclitaxel at doses of 175 mg/m2 or 135 mg/m2 is active and well tolerated in advanced breast cancer patients resistant to anthracyclines. The prophylactic use of colony-stimulating factors seems appropriate in heavily pretreated patients given the higher dose level.

Epirubicin in non-Hodgkin's lymphomas.

EPIRUBICIN (Epi-DX), a new analog of doxorubicin, was administered I.V. once q 3 weeks at the dose of 90 mg/m2 to 20 evaluable patients with non-Hodgkins lymphomas (NHL). Eighty-two percent of patients with favorable histology and 67% with unfavorable histology achieved complete or partial remissions, with an overall response rate of 75%. Gastrointestinal and hematologic toxicity was generally mild to moderate. Reversible ST-T changes were observed only in two patients. Epi-DX has high activity in patients with NHL, and further studies in combination with other agents are recommended.

Sequential Subcutaneous Thymopentin, Interferon Alpha-2A and Interleukin-2 in Metastatic Renal Cell Cancer

To determine the activity of sequential administration of thymopentin (TP-5), interferon alpha-2a (IFN) and interleukin-2 (IL-2) in metastatic renal cell cancer (RCC), 17 patients with RCC were treated with TP-5 50 mg/d on days 1 to 14, IFN 3 MIU/d on days 14, 15, 21, 22 and IL-2 18 MIU/d on days 16 to 20, and 23 to 27. Treatment was given subcutaneously and cycles were repeated every 6 weeks. All patients were assessed for toxicity and response. No objective responses were observed. Two patients had a short-lived disease stabilization. Median survival was 9 months. Toxicity was generally moderate. The most important side-effects were related to IL-2 administration. In view of the lack of antitumor activity, the combination of TP-5 + IFN + IL-2 in the doses and schedule used in this trial cannot be recommended. The investigation of chemotherapeutic and immunological agents that can effectively synergize with IFN or IL-2 is essential.

5-Fluorouracil, adriamycin and cyclophosphamide combined with high-dose medroxyprogesterone acetate in advanced breast cancer

Seventy-six patients with metastatic breast cancer were treated with fluorouracil, adriamycin (doxorubicin) and cyclophosphamide (FAC) plus high-dose medroxyprogesterone acetate (HD-MPA). MPA was given for 21 days at the dose of 500 mg/day i.m., then on a randomized basis, either 500 mg/week i.m. (FAC+HD-MPA i.m.) or 300 mg/day p.o. (FAC+HD-MPA p.o.). Objective response rates were 79% in 39 patients on FAC+HD-MPA i.m. and 73% in the 37 patients on FAC+HD-MPA p.o. There was no significant difference in the median duration of response and median survival for the 2 regimens (respectively, 17 months and 22 months, and 15 months and 21 months for FAC+HD-MPA i.m. and FAC+HD-MPA p.o.). Toxicity was mild and similar in both groups. Although FAC+HD-MPA was highly effective, at present it is difficult to select which regimen provides the best initial treatment for metastatic breast cancer.

Alternating combination chemotherapy of advanced soft tissue sarcomas in adults

THE POSSIBILITY OF IMPROVING TREATMENT RESULTS using an alternating combination chemotherapy was explored in 40 evaluable patients with advanced soft tissue sarcomas. Treatment regimen consisted of adriamycin and DTIC alternating with vincristine, actinomycin D, and cy-clophosphamide. Four patients achieved a complete response and eight achieved a partial response, with an overall response rate of 30%. The median duration of response was 14 months. The median survival time was 28 months for responders compared with 7 months for nonresponders (p = 0.001). Toxicity was predominantly limited to nausea, vomiting, and myelosuppression. Although this alternating regimen failed to improve response rates over other combinations, survival times observed in the present study should provide impetus to evaluate further the concept of sequential noncross-resistant combinations.