Phase I study of concurrent vinorelbine and radiation therapy in high-risk postmastectomy breast cancer patients

Background: Postmastectomy chest wall irradiation is recommended for high-risk breast cancer patients, such as those with ≥4 positive nodes. Irradiation is performed sequentially rather than concurrently with chemotherapy. However, the 5-year locoregional recurrence-free survival was statistically better in the concurrent method in node-positive patients in a prior study. The benefit of concurrent chemoradiotherapy for postmastectomy breast cancer patients is uncertain. Vinorelbine is often used as concurrent chemoradiotherapy for non-small cell lung cancer in Japan and has antitumor activity in breast cancer as well. Thus, we planned this dose-finding study of concurrent vinorelbine and radiation therapy in high-risk postmastectomy breast cancer patients. Methods: High-risk postmastectomy breast cancer patients were recruited. Patients received weekly vinorelbine administered concurrently with radiation therapy. The radiation dose was 50 Gy in 25 fractions over 5 weeks. Vinorelbine was administered weekly without a break, so the maximum number of vinorelbine cycles was five. A 3 + 3 dose-escalation design was used for determining maximal tolerable dose, recommended dose and safety. Results: A total of 10 patients were enrolled in cohorts of 10 and 15 mg/m². Dose-limiting toxicity was observed in one case in 10 mg/m² and two cases in 15 mg/m². Therefore, the maximal tolerable dose was defined at 15 mg/m² and the recommended dose was determined at 10 mg/m². The main adverse events included radiation dermatitis and neutropenia. Recurrence was observed in one patient with a median follow-up of 40 months. Conclusions: Concurrent vinorelbine and radiation therapy has a manageable safety profile at 10 mg/m² in high-risk postmastectomy breast cancer patients.