Phase I clinical trial to determine the feasibility and maximum tolerated dose of panitumumab to standard gemcitabine-based chemoradiation in locally advanced pancreatic cancer
Mené sur 14 patients atteints d'un cancer du pancréas de stade localement avancé, cet essai de phase I évalue la dose maximale tolérée, l'efficacité, du point de vue de la survie sans progression, et la toxicité du panitumumab dans le cadre d'un traitement combinant une chimiothérapie à base de gemcitabine et une radiothérapie
Purpose : Epidermal Growth Factor receptor (EGFR) inhibitors may improve both the therapeutic efficacy of radiotherapy and the radiosensitizing activity of gemcitabine. Based on this rationale and the non-overlapping toxicity profiles of gemcitabine and the monoclonal EGFR antibody panitumumab, we designed a phase I trial to investigate the maximum-tolerated dose (MTD), safety and activity of panitumumab added to gemcitabine-based chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer (LAPC). Patients and methods : Patients with LAPC and WHO Performance status 0-1 were treated with weekly panitumumab at four dose levels (1-2.5mg/kg), combined with weekly gemcitabine 300mg/m2 and radiotherapy (50.4Gy in 28 fractions) for 6 weeks, followed by gemcitabine 1000mg/m2 weekly for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. Each cohort was monitored during the combination therapy to establish dose limiting toxicity (DLT). Tumor evaluation was performed after CRT and during gemcitabine monotherapy. Results : Fourteen patients were enrolled; 14 were evaluable for toxicity and 13 for response. The MTD for panitumumab was 1.5mg/kg. Three of the 6 patients, treated at MTD, experienced grade 3 adverse events during the combination therapy; neutropenia (n=2; 33%), fatigue (n=1; 17%), nausea (n=1; 17%) and vomiting (n=1; 17%). Partial response was achieved by three patients (23%), one in each dose cohort. Median progression free survival (PFS) of the three cohorts together was 8.9 months. Conclusions: The addition of panitumumab to gemcitabine-based chemoradiotherapy in LAPC, has manageable toxicity and potential clinical efficacy.