Randomized phase II study of weekly paclitaxel with and without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA breast cancer without HER2 overexpression.

Abstract

Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response (pCR) rates. We evaluated the efficacy and safety of carboplatin and weekly paclitaxel (wPTX) followed by cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as neoadjuvant chemotherapy for HER2-negative breast cancer. Patients with stage II/IIIA HER2-negative breast cancer were randomly assigned to preoperatively receive CP-CEF (four 3-week cycles of carboplatin [area under the curve 5 mg/mL/min, day 1] and wPTX [80 mg/m(2), day 1, 8, 15] followed by four 3-week cycles of CEF [500/100/500 mg/m(2)] or P-CEF (four cycles of wPTX followed by four cycles of CEF). The primary objective was pCR rate. Of 181 eligible patients, 89 were randomly assigned to the CP-CEF and 92 to the P-CEF. Two patients in each arm refused to receive neoadjuvant chemotherapy. Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety. The pCR rate in the CP-CEF was significantly higher than that in the P-CEF (31.8 vs. 17.6 %, one-sided P = 0.01). Among patients with triple-negative breast cancer, the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [61.2 (23/37) vs. 26.3 % (10/38), P = 0.003]. Grade 3-4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF (65.9 vs. 38.5 %). Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity.

• Authors: Masashi Ando, Hideko Yamauchi, Kenjiro Aogi, Satoru Shimizu, Hiroji Iwata, Norikazu Masuda, Naohito Yamamoto, Kenichi Inoue, Shinji Ohono, Katsumasa Kuroi, Tetsutaro Hamano, Tamie Sukigara, Yasuhiro Fujiwara
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 145 Issue 2 Pg. 401-9 (Jun 2014) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 24728578 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Epirubicin
• Cyclophosphamide
• Carboplatin
• ERBB2 protein, human
• Receptor, ErbB-2
• Paclitaxel
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Carboplatin (administration & dosage)
• Cyclophosphamide (administration & dosage)
• Drug Administration Schedule
• Epirubicin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Middle Aged
• Neoadjuvant Therapy
• Neutropenia (chemically induced)
• Paclitaxel (administration & dosage)
• Receptor, ErbB-2 (metabolism)
• Treatment Outcome