Infusional paclitaxel and weekly vinorelbine chemotherapy with concurrent filgrastim for metastatic breast cancer: High complete response rate in a phase I-II study of doxorubicin-treated patients

Purpose: We investigated 96-hour paclitaxel infusion combined with weekly ( days eight and 15)vinorelbine as salvage therapy for metastatic breast canc er in anthracycline-exposed patients. All patients received scheduled suppo rt with granulocyte colony-stimulating factor (G-CSF; filgrastim). Tumor re sponse, toxicity, time to progression (TTP), and survival were assessed. Patients and Methods: This single-center nonrandomized trial enrolled 32 pa tients. Anthracycline exposure and subsequent progression were common to al l patients. Paclitaxel and vinorelbine were escalated over three dosing lev els, stratified by liver function. Results: Seven patients (22%) achieved a complete response and nine patient s achieved a partial response for an overall response rate of 50%. The medi an TTP was 6.1 months, and median survival time was 14.1 months. Dose-limit ing toxicity was neutropenia, with dose delay or reduction in seven of 32 p atients. Febrile neutropenia requiring hospitalization was uncommon (three of 32 patients; 9%), There were no treatment-related deaths. Grade 3/4 thro mbocytopenia occurred in two patients (6%), and 13 patients (41%) required RBC transfusions for anemia. Grade 3 nausea and vomiting was seen in one pa tient, who was found to be Addisonian. Despite potentially overlapping neur ologic toxicities of the two agents, only two patients (6%) were removed fr om the study because of progressive peripheral neuropathy. Conclusion: Administration of 96-hour paclitaxel infusion and subsequent we ekly vinorelbine with G-CSF support is well tolerated. The response rate, T TP, and survival data are encouraging for therapy given to anthracycline pr etreated patients with metastatic breast cancer. If these results can be ve rified in multi-institution trials, this or a similar combination of drugs would merit investigation as first-line therapy in this patient population, J Clin Oncol 17:1401-1412. (C) 1999 by American Society of Clinical Oncolo gy.