Phase II study of vinorelbine administered by 96-hour infusion in patientswith advanced breast carcinoma

BACKGROUND. Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in the treatment of patients with metastatic b reast carcinoma. Vinblastine given by 5-day continuous infusion showed a st eep dose-response curve. Pharmacokinetic studies of vinorelbine showed that it is possible to achieve a comparable antitumor effect with a smaller amo unt of the drug if it is given by continuous infusion. The purpose of this study was to determine the efficacy of vinorelbine given by 96-hour continu ous infusion to patients with refractory metastatic breast carcinoma patien ts. METHODS. Between May 1996 and August 1997, 47 patients with metastatic brea st carcinoma were registered into the study. All patients previously had re ceived doxorubicin and 70% had undergone prior paclitaxel treatment. Approx imately 56% of the patients had greater than or equal to 2 metastatic sites . All patients received vinorelbine according to the following dose schedul e: 8 mg bolus followed by 11 mg/m(2) by continuous infusion over 24 hours e very 4 days every 3 weeks. RESULTS. Forty-four patients were evaluable for response. A total of 193 cy cles were administered. The overall response rate was 16% (2 patients achie ved a complete response and 5 patients achieved a partial response). The me dian duration of response was 4.3 months and the median overall survival wa s 8.6 months. Patients with visceral metastases and/or multiple sites of in volvement had shorter durations of response than patients with only soft ti ssue disease or single-site metastasis (3.1 months vs. 4.9 months) and shor ter overall survival (8.1 months vs. 12 months). Dose reductions were neces sary due to cumulative stomatitis and/or fatigue in 12 cycles and neutropen ia and/or infection in 13 cycles. CONCLUSIONS. Due to toxicity, a revised maximum tolerated dose for continuo us infusion vinorelbine is proposed by the authors: 8 mg intravenously over 10 minutes followed by 10 mg/m(2) by continuous infusion over 24 hours eve ry 4 days. The current dose schedule did not offer an advantage either in r esponse rates or survival over the weekly vinorelbine bolus injection in do xorubicin-resistant and paclitaxtel-resistant patients. Cancer 1999;86:1251 -7. (C) 1999 American Cancer Society.