Gefitinib in Combination with Gemcitabine and Vinorelbine in Patients with Metastatic Breast Cancer Pre-treated with Taxane and Anthracycline Chemotherapy: A Phase I/II Trial

• Published in: Anticancer research 2008-09, Vol.28 (5B), p.3019-3025
• Main Authors: GIOULBASANIS, Ioannis, SARIDAKI, Zacharenia, KALYKAKI, Antonia, VAMVAKAS, Lambros, KALBAKIS, Kostas, IGNATIADIS, Michail, AMARANTIDIS, Kyriakos, KAKOLYRIS, Stylianos, GEORGOULIAS, Vassilis, MAVROUDIS, Dimitris
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anthracyclines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Bridged-Ring Compounds - therapeutic use; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Quinazolines - administration & dosage; Quinazolines - adverse effects; Taxoids - therapeutic use; Tumors; Vinblastine - administration & dosage; Vinblastine - adverse effects; Vinblastine - analogs & derivatives
• ISSN: 0250-7005; 1791-7530

Purpose: To determine the tolerability and efficacy of the combination of gefitinib with gemcitabine plus vinorelbine in metastatic breast cancer (MBC) patients, pre-treated with anthracyclines and taxanes. Patients and Methods: Women with measurable MBC pretreated with anthracycline- and taxane-based chemotherapy received oral gefitinib (250 mg/day) continuously combined with intravenous gemcitabine 1000 mg/m 2 and vinorelbine 25 mg/m 2 on day 1, every 2 weeks. The first 10 enrolled patients were evaluated for the safety and tolerability of the proposed fixed-dose regimen. Results: The study was discontinued prematurely due to low accrual. Twenty-five (71%) of the originally scheduled 35 patients received a total of 154 chemotherapy cycles. All the patients had previously received taxane- and 72% additionally anthracycline-based chemotherapy and 64% of them had progressive disease as best response to first-line treatment. Three episodes of dose-limiting toxicities (one non-febrile neutropenia grade 4 and two non-neutropenic infections grade 3) were observed in the safety analysis of the first 10 patients. In an intent-to-treat analysis, the overall response rate was 12% (95% CI, 0-24.7%), the median time to tumour progression was 3.5 months (range 1.0-11.5) and the median overall survival was 10.4 months (range 1.0-46.0). The main toxicity was hematological, with grade 3 and 4 neutropenia occurring in 6 (24%) and 4 (16%) patients, respectively. Febrile neutropenia occurred in 2 (8.0%) patients. Conclusion: Although well tolerated, the gefitinib plus gemcitabine and vinorelbine regimen achieved a low response rate in this prematurely terminated trial and therefore cannot be recommended for women with pre-treated MBC.