Phase I dose-finding study of eribulin and capecitabine for metastatic breast cancer: JBCRG-18 cape study

BACKGROUND: Eribulin is a nontaxane microtubule inhibitor with activity in patients with metastatic breast cancer (MBC). We conducted a phase I dose-finding study of eribulin and capecitabine in patients with MBC pretreated with anthracycline and taxane. METHODS: Women with MBC aged ≤70 years were enrolled. A 3 + 3 dose escalation design was used: level 0 dosing, eribulin (1.4 mg/m(2) intravenously on days 1 and 8) plus capecitabine [825 mg/m(2) orally twice daily (BID)]; 2-weeks-on, 1-week-off in a 21-day cycle. If there were no dose-limiting toxicities (DLTs), level 1 capecitabine dose was 1000 mg/m(2) BID. The primary objective was to determine maximum tolerated dose, DLTs, and recommended dose (RD). Secondary objectives included pharmacokinetics, safety, and best overall response rate. RESULTS: Nine women with MBC were enrolled; six at level 0, three at level 1. One patient had grade 4 DLTs at level 0 (serum creatinine 7.65 mg/dL and uric acid 13.4 mg/dL), considered associated with study drugs. Level 1 dosing was taken as the RD. Neutropenia was the most common ≥grade 3 toxicity. Pharmacokinetic parameters of eribulin were not influenced by co-administration of capecitabine. Of three patients in level 1, one achieved partial response and one had prolonged stable disease. CONCLUSION: Eribulin with capecitabine in the level 1 dosing schedule was associated with manageable toxicities and promising clinical activity. This combination is recommended for phase II investigation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12282-017-0798-4) contains supplementary material, which is available to authorized users.