Abstract
3585 Background: Epidermal growth factor receptor (HER1/EGFR) overexpression occurs in 45–80% of CRC patients (pts). Erlotinib (Tarceva™) is a potent HER1/EGFR inhibitor. Capecitabine and oxaliplatin have proven activity in MCRC pts. This trial determined the safety, the maximum tolerated dose (MTD) and pharmacokinetics (PK) of erlotinib in combination with capecitabine and oxaliplatin. Methods: MCRC pts were previously untreated or had received first-line treatment with 5-FU ± irinotecan. Patients were to receive escalating doses of daily oral erlotinib, capecitabine (days 1–14) (100mg + 1,650mg/m2 [Cohort 1]; 100mg + 2,000mg/m2 [Cohort 2]; 150mg + 2,000mg/m2 [Cohort 3]) and i.v. oxaliplatin 130mg/m2, every 21 days. Dose-limiting toxicity (DLT) was defined according to NCI-CTC criteria (2.0) in cycle 1 or 2. The MTD was the dose below which >1/3 pts had a DLT. Results: The first 6 pts in Cohort 1 had no DLTs. In Cohort 2, 2/6 pts had DLTs: one with G3 diarrhea and G3 intolerable rash; one with G3 diarrhea. Cohort 2 was expanded to 11 pts and two more pts experienced DLTs: one pt had G4 diarrhea and one pt had G3 pruritic rash. As 4/11 pts had DLTs, this cohort exceeded the definition of MTD. Thus, Cohort 1 was expanded to 12 pts and there were no DLTs in the additional pts. The most common adverse events (AEs) were diarrhea and rash. Preliminary evidence of antitumor activity was seen in both cohorts. Overall, 5 pts had a partial response (PR) and 14 had stable disease (SD). There was no evidence of PK interaction between erlotinib, capecitabine and oxaliplatin. Conclusions: These data indicate that capecitabine 1,650mg/m2 and oxaliplatin 130mg/m2 in combination with erlotinib 100mg/d is the recommended dose for phase II trials in MCRC pts. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
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