Phase I results from a study of lapatinib with gemcitabine and cisplatin (GC) in advanced/metastatic bladder cancer.

Abstract

252 Background: Lapatinib (Tykerb, Tyverb) is a potent EGFR and ErbB2 inhibitor approved for the treatment of breast cancer. GC is a standard chemotherapy regimen for advanced/metastatic bladder cancer and there are preclinical and clinical data suggesting the role of EGFR and HER2 in urothelial carcinoma. This phase I study examined the safety of lapatinib in combination with GC in patients (pts) with bladder cancer. Methods: The primary phase I objective was to determine the maximum tolerated dose of lapatinib 750–1,250 mg that could be administered safely with GC in bladder cancer pts. A 3+3 dose escalation was used with lapatinib 750 mg, 1000 mg and then 1250 mg. Lapatinib was dosed daily and G (1000 mg/m² days 1, 8, 15) + C (70 mg/m² day 2) every 28 days. Results: 18 pts with median age 63 yrs (range 50-77) and ECOG PS 0/1 (66.7% with WHO-PS 0 and 33.3% with WHO-PS 1) were included. 3/6, 3/5 and 6/7 pts completed at least one cycle according to the protocol and received lapatinib 750 mg, 1000 mg and 1250 mg + GC, in cohorts 1, 2 and 3, respectively. No dose-limiting toxicities (DLTs) occurred in cohort 1 or 2 (3 pts each); in cohort 3 (2 x 3 pts), 1 of 6 pts had DLT (Gr4 related febrile neutropenia and renal failure). One discontinued due to pt decision after 1 cycle. Ten pts received 6 cycles and one 7 cycles. The response rate among the 11/12 eligible patients was 73% (1 CR, 7 PR, 3 SD and 1 not assessable). Further toxicity data together with responses in relation to EGFR and HER2 status will be presented. Conclusions: Within the limits of a phase I study, lapatinib 750–1,250 mg + GC appears safe and tolerable with considerable activity at the maximum planned dose in bladder cancer. Clinical trial information: NCT00623064.