Page 32 - Demo

Chapter 230Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1, adequate hematological, hepatic (2.5 upper limit of normal, ULN) and renal function (estimated glomerular filtration rate >50 mL/min), normal calcium and magnesium levels. Patients with a history of allergic reactions to antibody treatment, impossibility of adequate radiation therapy, for example, due to tumor size, and patient suffering from any serious concomitant systemic disorders incompatible with the clinical study were considered not eligible. The institutional Medical Ethical board of the two participating centers, VU University Medical Center and the Academic Medical Center (both in Amsterdam, the Netherlands), approved the conduction of the trial (ClinicalTrials.gov Identifier: NCT01175733), which was in accordance with the Declaration of Helsinki and Good Clinical Practice. Written informed consent was obtained from all patients prior to inclusion into the study. Study treatmentThe treatment scheme is summarized in Fig. 1. The study was designed as 3 %u00fe 3 dose escalation clinical trial (23, 24). Panitumumab was administered weekly for 6 weeks by intravenous infusion in different dose levels per cohort (1, 1.5, 2, and 2.5 mg/kg) during gemcitabine-based CRT. Gemcitabine was administered weekly by intravenous infusion at a dose of 300 mg/m2 during RT in the first 6 weeks, followed by a dose of 1,000 mg/m2 weekly for 3 weeks every 4 weeks from day 50 until disease progression or unacceptable toxicity and otherwise continued for a maximum period of 1 year. The RT schedule consisted of a dose of 1.8 Gy per fraction for 28 days (total dose of 50.4 Gy) between days 1 and 38, on days 3 to 5 of the first week and on day 1 to 5 in the five consecutive weeks. The planning target volume for the radiation treatment consisted of all gross tumor on a 4D-CT scan including regional enlarged lymph nodes, enlarged with a 1.0-cm margin. The craniocaudal margin was extended with an extra 1 cm, when a 3D-CT scan was used. Typically, a multiple coplanar field technique or a volumetric modulated arc technique was used for treatment planning. Depending on the radiation oncology center (VUmc or AMC), either spinal column imaging or intratumoral fiducial markers were used for daily set-up. Follow-up lasted until death of the patient. In case of progressive disease, the choice of offering further treatment with palliative CHT was at the discretion of the treating physician.