A phase I study of capecitabine, oxaliplatin (CapOx), and lapatinib (L) in metastatic or advanced solid tumors

Abstract

2579 Background: CapOx is a standard treatment for patients (pts) with metastatic colorectal cancer (mCRC) and has been shown to be equivalent to FOLFOX in a phase III study. L is a tyrosine kinase inhibitor with targeting of the EGF and Her-2 receptors. Preclinical data suggest there may be synergy between L and Cap as well as L and Ox. This phase I study was designed to determine the maximum tolerated dose (MTD) of CapOx and L. Methods: Pts eligible for treatment included those with advanced or metastatic cancers, ECOG PS 2 or less, adequate renal and liver function, and ≤ 3 prior chemotherapy regimens. Treatment over a 21-day cycle was as follows: Ox, single IV infusion on Day 1; Cap, twice-daily oral administration on Days 1 through 14; L, continuous once-daily oral administration. Pts were treated with escalating doses of L (starting at 1000 mg daily) and Cap (starting at 1500 mg/m2/day), while Ox was kept at 130 mg/m2. The primary endpoint was determination of MTD. Results: Ten pts (9/10 female, median age 62 yrs.) were enrolled. One pt had breast cancer and the remainder had non- colorectal GI malignancies (esophagus, hepatobiliary, and pancreas). One pt at dose level 0 experienced dose-limiting toxicity (DLT) (dehydration, elevated bilirubin, hypokalemia). Two pts at dose level 1 (L 1000, Ox 130, Cap 2000) had DLTs of hypokalemia and diarrhea. At an intermediate dose level of L 1000, Cap 1700, Ox 130, two pts experienced DLTs (grade 2 fatigue/anorexia, grade 3 fatigue and dizziness). The MTD was determined to be L 1000 mg daily, Cap 1500 mg/m2/day, Ox 130 mg/m2. There were no treatment-related grade 4 toxicities. The most common grade 3 toxicity was diarrhea (4 pts). There were no grade 3 neuropathies, hematologic toxicities, or rash, and only one case of grade 3 fatigue. One pt with pancreatic cancer had a confirmed partial response (PR) to treatment, and 3 others had stable disease for > 90 days. Conclusions: The regimen of CapOx and L has efficacy in the treatment of solid tumors with established responsiveness to fluoropyrimidines or Ox. The MTD was L 1000 mg daily, Ox 130 mg/m2, and Cap 1500 mg/m2/day. This regimen will be investigated further in a Phase II study involving pts with mCRC. [Table: see text]