Phase II study of gemcitabine and carboplatin in metastatic breast cancers with prior exposure to anthracyclines and taxanes

• Published in: Investigational new drugs Vol. 28; no. 6; pp. 859 - 865
• Main Authors: Chan, Daniel, Yeo, Wee-Lee, Tiemsim Cordero, Maricel, Wong, Chiung-Ing, Chuah, Benjamin, Soo, Ross, Tan, Sing-Huang, Lim, Siew-Eng, Goh, Boon-Cher, Lee, Soo-Chin
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-12-2010; Springer Nature B.V
• Subjects: Adjuvants; Adult; Aged; Anemia; Anthracycline; Anthracyclines - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Carboplatin; Carboplatin - adverse effects; Carboplatin - therapeutic use; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug therapy; Female; gemcitabine; Hematology; Humans; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; Neutropenia; Oncology; Ovarian cancer; Pharmacology/Toxicology; Phase II Studies; Platelets; Survival; taxanes; Taxoids - therapeutic use; Thrombocytopenia; Toxicity; Transfusion; Treatment Outcome; Carboplatin; Anthracyclines and taxanes failure; Breast cancer; Gemcitabine
• DOI: 10.1007/s10637-009-9305-x
• EISSN: 1573-0646
• ISSN: 0167-6997

Summary
Background
Patients with metastatic breast cancer (MBC) are usually exposed to both anthracyclines and taxanes during neoadjuvant or adjuvant treatment of primary breast cancer or during initial therapy of MBC. We investigate the combination of gemcitabine and carboplatin in MBC with prior exposure to both anthracyclines and taxanes.
Patients and Methods
MBC patients previously treated with anthracyclines and taxanes were enrolled in a single tertiary center phase II study. Treatment consisted of gemcitabine (1,000 mg/m
2
I.V on days 1 and 8) and carboplatin (AUC 5 I.V on day 1) administered every 3 weeks.
Results
41 patients were recruited. Objective response rate was 39% including 1 complete response (2%) and 15 partial responses (37%). Twelve patients (29%) had stable disease. Median time to progression was 4.6 months (95% CI 3.3–5.9 months) and median overall survival 10.5 months (95% CI 7.6–13.4 months). Grade 3 & 4 hematological toxicities included neutropenia (58%), febrile neutropenia (15%), anemia (12%) and thrombocytopenia (49%), including 7% who required platelet transfusions. Non-hematological toxicity was rarely severe. 56% of patients required at least one dose reduction; the mean relative dose intensity for gemcitabine and carboplatin were 0.82 (range 0.5–1.0) and 0.95 (range 0.75–1.00) respectively, with no difference in dose intensity between responders and non-responders.
Conclusion
Gemcitabine combined with carboplatin has promising efficacy in MBC with prior treatment with anthracyclines and taxanes but has significant haematological toxicities requiring dose modifications. The regimen may be modified to gemcitabine 800 mg/m
2
 days 1 and 8 to improve tolerability.