Dual Targeting of the EGFR/HER2 Pathway in Combination with Systemic Chemotherapy in Refractory Pancreatic Cancer-The CONKO-008 Phase I Investigation

Background: Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF. Methods: We conducted a phase I trial using an accelerated dose escalation design in patients with refractory pancreatic cancer. Lapatinib was given on days 1 to 42 in combination with folinic acid 200 mg/m(2) day + 5-fluorouracil 2000 mg/m(2) (24 h) on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m(2) days 8 and 22 of a 43-day cycle (OFF). Toxicity and efficacy were evaluated. Results: In total, eighteen patients were enrolled: dose level 1 (1000 mg) was assigned to seven patients, dose level 2 (1250 mg), five patients; and dose level 3 (1500 mg), six patients. Dose-limiting toxicities were diarrhea and/or neutropenic enterocolitis observed in two of six patients: one diarrhea III degrees, one diarrhea IV degrees, as well as neutropenic enterocolitis. The maximum tolerable dose of lapatinib was 1250 mg OD. Conclusions: The combination of lapatinib 1250 mg OD with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation.

Automated summary

This study aimed to determine the maximum tolerable dose of lapatinib in combination with platinum-containing chemotherapy in refractory pancreatic cancer, and to evaluate its safety and efficacy. The maximum tolerable dose was found to be 1250 mg/day, and the combination of lapatinib with platinum-containing chemotherapy was deemed safe in patients with refractory pancreatic cancer.