A phase I trial of lapatinib in combination with carboplatin in patients with platinum sensitive recurrent epithelial ovarian cancer

Abstract

14106 Objective: Lapatinib is an inhibitor of EGFR and ErBb-2 tyrosine kinase. It has demonstrated anti-tumor activity in preclinical trials. Early trials evaluated toxicities and doses in several tumors types, however very few ovarian cancer patients have been included in lapatanib trials. The primary objective of this study was to determine the nature and degree of toxicity as well as the maximum tolerated dose (MTD) of Lapatinib in combination with carboplatin when used as second line therapy for platinum sensitive, recurrent ovarian or primary peritoneal carcinoma. The secondary outcome includes preliminary evaluation of response to therapy. Methods: After obtaining IRB approval, patients with measurable, recurrent, platinum sensitive epithelial ovarian or primary peritoneal carcinoma were eligible for enrollment. Patient cohorts were treated with intravenous (IV) carboplatin (AUC 6) every 21 days in combination with escalating dosages of daily oral lapatinib for 6 planned cycles. Toxicity was assessed using NCI Common Terminology Criteria for Adverse Events. Response and time to documented progression were also monitored. Results: Nine patients have been enrolled in 2 cohorts to date. Six women with recurrent cancer were administered eighteen cumulative cycles of IV carboplatin and 750 mg of oral lapatinib and were evaluable for toxicity data. The most common toxicity was hematologic with 8 (44%) cycles effected by grade 3 or 4 neutropenia or thrombocytopenia. Two patients were taken off the study secondary to excessive delay for hematologic depression. The dose of carboplatin was reduced to an AUC 5 in the second cohort due to excessive hematologic toxicity and treatment delay. Grade 3 nonhematologic toxicities consisted of abdominal pain (38%), indigestion (6%), fatigue (6%), and urinary frequency (11%). One patient withdrew due to abdominal pain not related to the study drug. Two subjects were evaluable for response. As indicated by biochemical and radiographic examination, both had a complete response and have no evidence of disease. Conclusions: Lapatinib, in combination with IV carboplatin at an AUC 5, portrays an acceptable toxicity profile and antitumor activity. Accrual to cohorts of escalating lapatinib doses is ongoing. No significant financial relationships to disclose.