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Chapter 236Table 3. Median PFS and OS for each dose cohort1 mg/kg 1,5 mg/kg 2,0 mg/kgn 3* 6** 5Median PFS(per cohort)11.0 11.8 4.3median OS(per cohort)19.5 17.0 9.1*One patient in the 1 mg/kg cohort is not assessable for tumor response, PFS and OS**In the 1,5 mg/kg cohort 1 patients were progression free at evaluation and 2 patients were alive at evaluation.Discussion Here, we report the results of a phase I study designed to determine the safety, tolerability, and potential clinical efficacy of the anti-EGFR mAb panitumumab added to standard gemcitabine-based CRT in patients with LAPC. The MTD of panitumumab was determined to be 1.5 mg/kg. We concluded that adding panitumumab to gemcitabine-based CRT is feasible with considerable, but manageable toxicity, as expected based on the non- overlapping toxicity profile of CRT and panitumumab. No differences in performance status, nodal status (Table 1), comorbidity, intensity of RT (tumorsize and radiation fields were equal between the cohorts; Supplementary Table S2), or dosing of gemcitabine by itself could explain the observed DLTs in cohort three compared with the other two cohorts and were therefore most likely caused by the addition of a higher dose of panitumumab to the combination treatment. Major toxicities potentially related to the addition of panitumumab were nausea, vomiting, neutropenia, fatigue, and anorexia, whereas acneiform rash was considered to be definitively related. These toxicities, apart from skin toxicity (22), are not common for treatment with anti-EGFR mAb treatment, and are likely to be predominately caused by the combination with gemcitabine-based CRT (8, 27). In addition, patients with LAPC often suffer from fatigue and gastrointestinal symptoms such as nausea and vomiting, even without treatment. Because of these common gastrointestinal problems and the small number of patients per cohort in this study, we cannot rule out that establishing the MTD might be influenced by mild differences of gastrointestinal or even other complaints in the three cohorts before start of treatment. How- ever, these differences were not clinically recognized despite intensive observation and there is no evidence of objective measurable differences that may have influenced