Purpose: This phase I study explored gefitinib (G) and capecitabine (C) in metastatic breast cancer (MBC).
Methods: Sequential cohorts (n = 3) received G and escalating C on a 14 day on/7 day off schedule, with a validation cohort (n = 10) at the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was defined in cycle 1. The primary endpoint was safety; secondary endpoints included response and adherence.
Results: About 19 patients were treated for a median of 5 cycles. No patients in sequential cohorts experienced DLT; C MTD was 2,000 mg/m(2)/day when paired with daily G 250 mg. In the validation cohort, four experienced serious toxicities, including diarrhea, mucositis, and palmarplantar dysesthesia. At the MTD, 6 (46%) required a C dose reduction, and 3 (23%) came off study for toxicity. One partial response was observed (8%, 95% CI 0.2-38.5%); five had stable disease >24 weeks (26, 95% CI 9-51%). Patients missed few drug doses, with the suggestion of overadherence to therapy.
Conclusions: In this phase I study of G and C in MBC, a C MTD was identified, and significant toxicity was observed. About 8% demonstrated a response, with 26% maintaining stable disease. The possibility of overadherence, as suggested in this study, may have implications for other trials of oral antineoplastic therapy.