Erlotinib + gemcitabine in patients with unresectable pancreatic carcinoma: Results from a phase IB trial

Abstract

4110 Background: Erlotinib (Tarceva) is a reversible inhibitor of HER1/EGFR tyrosine kinase. It has demonstrated antitumor activity in various epithelial malignancies and additive antitumor effect when combined with chemotherapy drugs. The purpose of this trial was to evaluate the tolerability and preliminary activity of escalating doses of erlotinib given in combination with standard-dose gemcitabine (GEM 1000 mg/m2). Methods: Eligible patients included those with advanced pancreatic carcinoma or other malignancies potentially responsive to GEM. In the escalating phase of the trial patients with pancreatic and non-pancreatic carcinomas were enrolled in sequential cohorts using 100 mg or 150 mg oral daily dosing of erlotinib. GEM 1000 mg/m2 was given weekly for 7 weeks (1st cycle), then weekly x 3 every 4 weeks (subsequent cycles). Preliminary results from the dose-escalating phase of this trial were previously reported (ASCO 2003). After establishing tolerability, additional gemcitabine-naïve patients with pancreatic cancer were enrolled. Overall, we have enrolled 14 patients with unresectable pancreatic carcinoma: 2 patients at the 100 mg dose level of erlotinib and 12 patients at the 150 mg dose level. Characteristics: measurable or evaluable disease, gender M/F 7/7, median age 66 yrs (range 45–82), median PS 90 % KS (range 80–100%). Results: 1 partial response (PR, 7%), 3 minor responses and 6 with stable disease for an overall disease control rate of 70 % (PR+SD), and 4 patients progressed (PD, 30%). The median duration of study treatment was 4 months (range from 2 to 12+) with 4 patients remaining on study treatment. The most common toxicities included skin rash, neutropenia, fatigue, nausea and diarrhea. The full PK analysis is ongoing and will be updated at the time of meeting. Conclusion: The erlotinib + gemcitabine combination appears promising, with a high rate of disease stabilization and acceptable toxicity profile seen in patients with unresectable pancreatic carcinoma. This combination is currently being compared to standard GEM therapy in a phase III randomized trial conducted by the NCIC. Supported by grant from OSI Pharmaceuticals. No significant financial relationships to disclose.