title: Phase I study of concurrent vinorelbine and radiation therapy in high-risk postmastectomy breast cancer patients.
abstract: 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/m(2). Dose-limiting toxicity was observed in one case in 10 mg/m(2) and two cases in 15 mg/m(2). Therefore, the maximal tolerable dose was defined at 15 mg/m(2) and the recommended dose was determined at 10 mg/m(2). 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/m(2) in high-risk postmastectomy breast cancer patients.
authors.affiliation: Department of Medical Oncology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan. kh99081@yahoo.co.jp.|Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, 466-8560, Japan. kh99081@yahoo.co.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Breast and Endocrine Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Riku
authors.affiliation: Department of Breast and Endocrine Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Iwase
authors.affiliation: Department of Radiotherapy, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hirasawa
authors.affiliation: Department of Radiotherapy, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Breast and Endocrine Surgery, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Medical Oncology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawada
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008408:Mastectomy; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine
keywords: Breast cancer; Phase I study; Radiation therapy; Vinorelbine