Τίτλος:
Weekly Paclitaxel and Carboplatin Plus Bevacizumab as First-Line Treatment of Metastatic Triple-Negative Breast Cancer. A Multicenter Phase II Trial by the Hellenic Oncology Research Group
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Metastatic triple-negative breast cancer lacks a standard therapeutic strategy and represents an unmet need for novel therapies. We conducted a phase II study to evaluate the weekly paclitaxel/carboplatin/bevacizumab combination. Forty-six patients were enrolled and 7 (15.2%) complete and 23 (50%) partial responses were observed for an objective response rate of 65.2% with tolerable toxicity. The combination merits further clinical evaluation. Background: Triple-negative breast cancer (TNBC) lacks a standard targeted therapeutic strategy and is treated with conventional cytotoxic agents. Because of the sensitivity of TNBC to platinum compounds and the synergistic effect of bevacizumab with paclitaxel we investigated the efficacy and toxicity of weekly paclitaxel and carboplatin in combination with bevacizumab as first-line treatment in metastatic TNBC. Patients and Methods: This phase II study followed the Simon's 2-stage optimal design. Paclitaxel (90 mg/m 2 ) and carboplatin (2 area under the curve) were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15. The primary end point was the objective response rate (ORR). The null hypothesis that the ORR is ≤ 40% could be rejected if the number of objective responses was ≥ 23 among 46 evaluable patients. Results: A total of 46 patients were enrolled. Seven (15.2%) complete and 23 (50%) partial responses were observed for an ORR of 65.2% (95% confidence interval, 52.9%-80.4%). The median progression-free survival was 10.3 months, the median overall survival 25.7 months, and the median duration of response 18.2 months. Neutropenia Grade III and IV was experienced by 13 (28.3%) and 6 (13.04%) patients, respectively. One patient developed an uneventful Grade IV thrombocytopenia. There was 1 toxic death due to febrile neutropenia. Other Grade III toxicities included anemia (n = 2), neurotoxicity (n = 2), thrombocytopenia (n = 1), and diarrhea (n = 1). No serious bevacizumab-related toxicities were observed. Conclusion: The study achieved its primary end point by showing clinical activity for weekly paclitaxel with carboplatin and bevacizumab combination. This regimen merits further evaluation in this setting. © 2017 Elsevier Inc.
Συγγραφείς:
Saloustros, E.
Nikolaou, M.
Kalbakis, K.
Polyzos, A.
Christofillakis, C.
Kentepozidis, N.
Pistamaltzian, N.
Kourousis, C.
Vamvakas, L.
Georgoulias, V.
Mavroudis, D.
Περιοδικό:
Clinical Breast Cancer
Εκδότης:
W B SAUNDERS CO-ELSEVIER INC
Λέξεις-κλειδιά:
bevacizumab; carboplatin; paclitaxel; antineoplastic agent; bevacizumab; carboplatin; paclitaxel, adjuvant chemotherapy; adult; aged; anemia; Article; asthenia; bleeding; bone metastasis; brain metastasis; cancer combination chemotherapy; cancer radiotherapy; cancer surgery; cancer survival; clinical article; clinical evaluation; constipation; diarrhea; drug efficacy; drug potentiation; drug tolerability; febrile neutropenia; female; human; hypertension; intraductal carcinoma; leukopenia; liver metastasis; lobular carcinoma; lung metastasis; lymph node metastasis; median survival time; metastatic breast cancer; multicenter study; nausea and vomiting; neoadjuvant chemotherapy; neurotoxicity; overall survival; perforation; phase 2 clinical trial; progression free survival; stomatitis; thrombocytopenia; treatment response; triple negative breast cancer; anemia; chemically induced; clinical trial; diarrhea; drug administration; intravenous drug administration; middle aged; mortality; neutropenia; pathology; severity of illness index; thrombocytopenia; triple negative breast cancer, Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carboplatin; Diarrhea; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Middle Aged; Neutropenia; Paclitaxel; Progression-Free Survival; Severity of Illness Index; Thrombocytopenia; Triple Negative Breast Neoplasms
DOI:
10.1016/j.clbc.2017.10.013
