Phase I/II study of gemcitabine in association with vinorelbine for metastatic breast cancer

• Published in: Breast cancer research and treatment Vol. 70; no. 3; pp. 163 - 169
• Main Authors: MARIANI, G, TAGLIABUE, P, ZUCCHINELLI, P, BRAMBILLA, C, DEMICHELI, R, VILLA, E, MARCHIANO, A, VALAGUSSA, P, BONADONNA, G, GIANNI, L
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.12.2001; Springer Nature B.V
• Subjects: Adult; Aged; Agranulocytosis - chemically induced; Agranulocytosis - drug therapy; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Cancer research; Cancer therapies; Chemotherapy; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Drug Administration Schedule; Female; Humans; Maximum Tolerated Dose; Medical sciences; Menopause; Middle Aged; Pharmacology. Drug treatments; Vinblastine - administration & dosage; Vinblastine - adverse effects; Vinblastine - analogs & derivatives; Vinorelbine; Antineoplastic agent; Human; Drug combination; Intravenous administration; Gemcitabine; Toxicity; Malignant tumor; Mammary gland diseases; Increasing dose; Alkaloid; Chemotherapy; Treatment; Phase II trial; Phase I trial; Female; Advanced stage; Drug interaction; Fluorine Organic compounds; Mammary gland; Pyrimidine nucleoside; Vinorelbine
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1023/A:1013034311284

Gemcitabine (G) and vinorelbine (V) have favorable safety profile and antitumor activity in metastatic breast cancer. To exploit their different mechanism of action and lack of overlapping toxicity, we performed a phase I and II study of G and V in combination. Fifty-three patients with metastatic breast cancer were treated. In the dose-finding phase, seven cohorts of patients (22 women) received increasing doses to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination. Patients recruited in the phase II portion of the study (31 women) received the dose level immediately below the one defined as MTD (i.e., G 1200 mg/m2, V 30 mg/m2, on day 1 and day 8, every 3 weeks). Dose escalation was discontinued at G 1400mg/m2 and V 30 mg/m2 because of toxic death due to thrombocytopenia and CNS hemorrage. No other limiting toxicities were observed, and tolerability was similar at all dose levels studied in the escalation portion of the study. The main toxicity was granulocytopenia of grade 3/4 in 36 and 48% of the patients on phase I and II respectively, without episodes of neutropenic fever. Thrombocytopenia was uncommon. Other side effects were usually mild to moderate. In 46 evaluable patients, the response rate was 24% (complete response 7%, partial response 17%). Disease stabilization was observed in further 17%. The median duration of response was 12 months (range 5-14) and the median survival was 20 months (range 1 to 45+). G and V, on day 1 and 8 of 3-weekly cycles, can safely be administered to patients with metastatic breast cancer at the dose of 1200 and 30 mg/m2, respectively. The antitumor activity of G and V in combination was similar to that reported when using either drug as single agent.