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Panitumumab and chemoradiation for inoperable pancreatic cancer372gastrointestinal complaints between the cohorts except for the difference in combination treatment (e.g., higher dose of panitumumab in cohort 3 compared with cohorts 1 and 2). Whether this combination treatment is of clinical benefit needs to be studied in the phase II part of this study. The first preliminary results on this small study population with a median PFS and OS of respectively 11.8 and 17.0 months in the MTD cohort suggest some efficacy. However, a true comparison of efficacy related to the different dose cohorts is not possible due to the small numbers of patients. OS and PFS were relatively short for patients treated in the high-dose cohort, while having comparable base line characteristics compared with patients in the MTD cohort (respectively 60% vs. 50% WHO PS 0 and respectively 90% vs. 83% elevated baseline Ca 19.9). The distribution of T4 tumors was also equal between the different cohorts. Multiple studies included targeted therapy. Different CHT schedules and RT modalities report variable outcomes without a clear advantage of one treatment schedule. Our previous reports on chemoradiation for LAPC revealed a median survival of 10 months for the combination of gemcitabine 300 mg/m2 weekly with RT (24 Gy in three consecutive weekly fractions of 8 Gy) (27) and for the combination of UFT 300 mg/m2 daily, leucovorin 30 mg and celecoxib 800 mg daily for 28 days concomitant with RT (20 x 2.5Gy) (28). In the present trial, radiation and CHT seemed to be better tolerated compared with our previous studies. The day to day position variation (29) of pancreatic tumors and their intrafraction motion (30) due to breathing pose are challenging concerns in RT of LAPC. Currently, we tackle these issues by performing image guided radiation therapy (IGRT), using gold fiducial markers (31). Our study is the first clinical trial in which panitumumab is combined with gemcitabine-based CRT in LAPC. Previously, the combination of panitumumab 6 mg/kg on days 1, 15, and 29 in combination with 5FU/capecitabine-based CRT followed by gemcitabine and panitumumab followed by maintenance panitumumab for 6 months in LAPC was reported at ASCO 2012 (32). At a median follow-up of 12.3 months, median OS and PFS were 12.1 and 7.4 months, respectively. AEs (67% grade 3 and 20% grade 4), especially during the chemo-RT portion, were considerable and affected administration of subsequent systemic maintenance therapy. The observed toxicities in the current dose finding study suggest that the panitumumab dose was too high, at least during CRT. Other anti