Page 33 - Demo

Panitumumab and chemoradiation for inoperable pancreatic cancer31Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9Week 10 %u2026..2Panitumumab (day 3-5 of the firstweek; day 1-5 of the 5 followingweeks)Radiotherapy *Gemcitabine on day 1**** From week 8 and further Gemcitabine will be administered as monotherapy * 1.8 Gy for 28 days (in total 50.4 Gy) between days 1 and 38 Figure 1. Treatment schedule for patients with LAPC. Toxicity evaluation, dose escalation rules, and response assessment Dose limiting toxicity (DLT) and adverse events (AE) were graded by the NCI Common Terminology Criteria of Adverse Events (CTC-AE) grading system version 3.0 (25). Patients were continuously monitored for toxicity. Patients were enrolled per dose level in cohorts of 3. At the final dose level, a minimum of 6 patients were treated to determine the MTD, defined as less than 2 patients out of 6 with a DLT. DLTs were defined as any of the following hematologic events during the first 43 days from start of combination treatment and attributable to combination therapy: febrile neutropenia, neutropenic infection, grade 4 neutropenia lasting over 7 days, grade 3 thrombocytopenia for >7 days, and grade 4 thrombocytopenia. Non-hematological DLTs included grade 3 nausea, vomiting, or diarrhea despite optimal medical support, grade 3 fatigue persisting >7 days, or grade 4 fatigue. Any other grade 3 AE (except alopecia), failure to recover from related toxicities to grade 1 or baseline severity (or grade 2 at investigator and sponsor discretion) after delaying the next cycle up to 7 days and failure to complete the first 6 weeks of treatment (75% of planned dose of RT, gemcitabine, and panitumumab) were also considered as a DLT. Mucositis, diarrhea, dermatitis, and rash were considered as specific panitumumab-related toxicities. The use of prophylactic treatment for skin toxicities was allowed. All patients underwent a baseline CT scan and an efficacy evaluation CT after chemoradiation, during gemcitabine monotherapy at 3, 5, 7, and 9 months and every 3 months thereafter until progressive disease. The RECIST version 1.1 (26) were used for response assessment. Time to progression (TTP), mentioned in the study protocol as secondary endpoint, was defined as the time from registration in the study to progression or death, whichever came