Phase II Trial of Gemcitabine/Carboplatin (plus Trastuzumab in HER2-Positive Disease) in Patients with Metastatic Breast Cancer

• Published in: Clinical breast cancer 2008-04, Vol.8 (2), p.178-186
• Main Authors: Loesch, David, Asmar, Lina, McIntyre, Kristi, Doane, Lisa, Monticelli, Michael, Paul, Devchand, Vukelja, Svetislava, Orlando, Mauro, Vaughn, LaTrice G, Zhan, Feng, Boehm, Kristi A, O'Shaughnessy, Joyce A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asthenia; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Carboplatin - administration & dosage; Carboplatin - adverse effects; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Female; Hematology, Oncology and Palliative Medicine; HER2/ neu; Humans; Kaplan-Meier Estimate; Middle Aged; Monoclonal antibodies; Neoplasm Metastasis - drug therapy; Neoplasm Metastasis - pathology; Neutropenia; Obstetrics and Gynecology; Receptor, ErbB-2 - metabolism; Trastuzumab
• ISSN: 1526-8209; 1938-0666
• DOI: 10.3816/CBC.2008.n.019

Abstract Background Gemcitabine and carboplatin have significant preclinical synergy, and both provide synergistic antitumor activity in metastatic breast cancer (MBC) when used in combination with trastuzumab. The gemcitabine/cisplatin combination is highly active in MBC with response rates (RRs) of approximately 50% in anthracycline-and taxane-pretreated patients and up to 80% in untreated subjects. This phase II trial studied the efficacy and safety of gemcitabine/carboplatin with or without trastuzumab in patients with MBC. Patients and Methods Patients were stratified into 3 groups: group 1, HER2-positive; group 2, HER2-negative and taxane-naive/remote (no taxanes within past 2 years); and group 3, HER2-negative and previous taxane therapy. Included were women aged ≥ 18 years, Eastern Cooperative Oncology Group performance status of 0-2, with Response Evaluation Criteria in Solid Tumors–defined measurable MBC; HER2-negative or HER2 (3+) by immunohistochemistry or fluorescence in situ hybridization positive. All cycles were repeated every 14 days. On day 1, gemcitabine 1500 mg/m2 over 30 minutes was administered followed by carboplatin area under the curve of 2.5. Group 1 also received trastuzumab 8 mg/kg on day 1 of each cycle followed by 4 mg/kg for every 2 weeks thereafter. Results One hundred fifty patients were registered (50, 51, and 49 in groups 1, 2, and 3, respectively). The overall RRs were 64%, 27%, and 32%, respectively, with median time to progression of 7.2, 5.5, and 4.4 months, respectively. Overall, grade 3/4 toxicities included neutropenia (45%), leukopenia (17%), and thrombocytopenia (7%). Alopecia was infrequent: grade 1 (34%) and grade 2 (3%), and there was no significant cardiac toxicity. Conclusion Gemcitabine/carboplatin/trastuzumab is highly active in patients with HER2-positive MBC. Gemcitabine/carboplatin is active in patients with HER2-negative MBC independent of previous taxane therapy. Gemcitabine/carboplatin with or without trastuzumab administered every 2 weeks is associated with a low frequency of serious toxicity.