Efficacy and toxicity of vinorelbine with doxorubicin/cyclophosphamide combination chemotherapy in a phase I-II study for advanced or recurrent breast cancer patients

• Published in: Breast cancer (Tokyo, Japan) Japan), 2006, Vol.13 (2), p.159-165
• Main Authors: Saeki, Toshiaki, Takashima, Shigemitsu, Ogita, Masami, Tabei, Toshio, Adachi, Isamu, Tamura, Kazuo, Takatsuka, Yuichi, Kanda, Kazuhiro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cause of Death; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Dose-Response Relationship, Drug; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Drug Administration Schedule; Female; Humans; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Patient Selection; Prognosis; Risk Assessment; Survival Rate; Treatment Outcome; Vinblastine - adverse effects; Vinblastine - analogs & derivatives; Vinblastine - therapeutic use
• ISSN: 1340-6868; 1880-4233
• DOI: 10.2325/jbcs.13.159

To evaluate the efficacy and toxicity of vinorelbine (VNB) with doxorubicin/cyclophosphamide (AC) combination chemotherapy, a phase I-II study was carried out in patients with advanced or recurrent breast cancer. The phase I part of this study was carried out to determine the treatment schedule and acceptable dose of VNB for the phase II study. In phase I, VNB was initially given as a short infusion on days 1, 8 and 15, every 4 weeks. The initial dose of vinorelbine was 15 mg/m2. In the AC regimen, 20 mg/m2 of doxorubicin (ADM) was given intravenously (i.v.) on days 1 and 8, and 100 mg/body of cyclophosphamide (CPA) was administered orally from days 1 to 14. Subsequently, a phase II study was carried out at the maximum acceptable dose (MAD). Twenty-three patients were entered into this study. In patients receiving VNB at a dose of 15 mg/m2, neutropenia (> or = grade 3) frequently occurred on day 15. The treatment schedule of this study was therefore changed to VNB given i.v. on days 1 and 8 with AC combination chemotherapy. In this treatment schedule, grade 4 neutropenia lasting for more than 4 days occurred in patients given VNB at a dose of 20 mg/m2 with AC more frequently than in those given 15 mg/m2 of VNB. Therefore, the MAD of VNB was determined to be 20 mg/m2 in this regimen. At this recommended dose, there were 1 complete (CR) and 8 partial responses (PRs) in 15 patients, with an overall response rate of 60.0%. No treatment-related death occurred. These data indicate that VNB plus AC combination chemotherapy was effective and well tolerated for breast cancer patients. A randomized trial of VNB plus AC vs. AC combination chemotherapy may be required to ascertain the benefit of this regimen for advanced or recurrent breast cancer patients.