PACLITAXEL ACTIVITY IN HEAVILY PRETREATED BREAST-CANCER - A NATIONAL-CANCER-INSTITUTE TREATMENT REFERRAL CENTER TRIAL

Purpose: To provide paclitaxel, an investigational drug at the incepti on of this study, to women with chemotherapy-refractory metastatic bre ast cancer and to evaluate response and toxicity in these patients. Pa tients and Methods: Two hundred sixty-seven patients with progressive disease (PD) following at least two chemotherapy regimens for metastat ic breast cancer and a contraindication to further doxorubicin treatme nt received paclitaxel either at 175 mg/m(2) intravenously (IV) over 2 4 hours or at 135 mg/m(2) if they herd prior irradiation to 30% of mar row-bearing bone or ct cumulative dose of mitomycin greater than or eq ual to 20 mg/m(2). Results: In a subgroup of patients (n = 172) with m easurable disease, four complete responses (CRs) and 36 partial respon ses (PRs) occurred, for an overall response rate of 23% (95% confidenc e interval [Cl], 17% to 30%). No differences in response rates were no ted according either to the number of prior chemotherapy regimens rece ived or to whether patients were considered refractory to doxorubicin. The dose and schedule used in this trial resulted in febrile neutrope nia in 45% of patients and a hospitalization rate of 49%. Conclusion: paclitaxel's activity in this multiinstitutional trial in heavily pret reated patients confirms the encouraging results attained in single-in stitution trials. Although at this dose and schedule paclitaxel may be considered too myelosuppressive for palliative core, supportive measu res such as colony-stimulating factors and antibiotics were not used p rophylactically. Current research efforts are focusing on whether pacl itaxel's activity against breast cancer is dose- and/or schedule-depen dent, and on what role if has in patients with less advanced disease.