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Panitumumab and chemoradiation for inoperable pancreatic cancer332DLT and maximum-tolerated and safe dose No DLTs were observed in the first 3 patients in the first and second dose level (1 and 1.5 mg/kg panitumumab). Two of the 5 patients treated in the third dose level (2 mg/kg panitumumab) experienced a DLT and therefore this dose level was considered non-tolerable. One of these patients fulfilled the DLT criteria, because of nausea grade 3 despite optimal medical support, including hospitalization. This was reported as a serious adverse event (SAE) related to panitumumab in combination with gemcitabine and RT. The other patient experienced a DLT based on failure to complete the first 6 weeks of treatment as defined by the protocol, due to multiple grade 1 to 2 toxicities. The next 3 patients were enrolled in the second dose level (1.5 mg/kg) and none had a DLT, providing the MTD as defined in the protocol. Toxicity was manageable at a panitumumab dose of 1.5 mg/kg (MTD). All 6 patients in this dose cohort experienced some grade of nausea and vomiting and 3 of the 6 patients experienced one or more (possibly) treatment-related grade 3 AEs during the first 43 days of treatment. One patient experienced neutropenia, the second patient experienced neutropenia, nausea, and vomiting, and the third patient experienced fatigue. These AEs were manage- able and resolved within 4 days (nausea and vomiting), 5/6 days (neutropenia), and 6 days (fatigue). No grade 4 AEs were observed at the MTD. All AEs during CRT with panitumumab are listed in Table 2. Rash, nausea, vomiting, weight loss, taste alteration, diarrhea, paronychia, and dermatitis are considered as (possible) panitumumab-related AEs. Four patients experienced hypomagnesaemia grade 1, 3 patients only during CRT, 1 patient also during the first 2 months of gemcitabine monotherapy. A total of 12 SAEs were reported in 8 of the 14 study participants, which were evaluable for toxicity. Only one SAE was related to the study treatment. AEs reported after the CRT period (first 43 days) of the study are listed in Supplementary Table S1. No unexpected AEs were reported during gemcitabine monotherapy. Table 2. Adverse events during chemoradiation with panitumumab (maximum grade of each AE per patient) during the chemoradiation with panitumumab (first 43 days)AE, n (%)Cohort 1.0 mg/kg (n =3)Cohort 1.5 mg/kg (n =6)Cohort 2.0 mg/kg (n =5)Grade 1/2 Grade 3/4 Grade 1/2 Grade 3/4 Grade 1/2 Grade 3/4Blood/bone marrowThrombocytopenia%u2014%u20142 (33)%u2014 %u2014 %u2014Neutropenia %u2014 %u2014 2 (33) 2 (33) %u2014 1 (20)