Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial.

BACKGROUND: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m² day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m² d1) and capecitabine (650-800 mg/m² b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. RESULTS: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m² d1, d8; oxaliplatin 130 mg/m² d1 and capecitabine 650 mg/m² b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. CONCLUSION: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigations.

Induction chemotherapy followed by parenchyma-sparing surgery in medically inoperable NSCLC-results of a feasibility study.

PURPOSE: Feasibility trial to test the toxicity and outcome of three cycles of induction chemotherapy followed by limited surgery in medically inoperable early stage NSCLC patients. PATIENTS AND METHODS: Thirteen patients with NSCLC (stages I-IIIB) with insufficient cardio-respiratory reserves for the oncologically required lung resection, received three cycles of induction chemotherapy with cisplatin (100mg/m(2)) and docetaxel (85mg/m(2)) followed by parenchyma-sparing lung surgery. Operability was evaluated with pulmonary function tests, perfusion scintigraphy and cardiopulmonary exercise testing. In selected patients coronary angiography or myocardial perfusion scintigraphy was performed. Rate of R0-resections was taken as primary outcome. RESULTS: Twelve of 13 patients received the three cycles of chemotherapy as planned. The main grade 3/4 hematological toxicity was neutropenia (62%), non-hematological toxicity was neutropenic fever (23%) and cough/dyspnea (31%). Complete, partial and stable responses to chemotherapy were seen in 1, 10 and 2 patients, respectively-the overall response rate was 85%. No patient had tumor progression. Eleven/13 (85% (CI 95% 54, 97) %) patients underwent surgery (4 lobectomies, 2 segmentectomies, and 5 wedge resections), all had a pathologically complete resection of the tumor. There was one postoperative death due to myocardial infarction. The median disease-free and overall survivals were 57(CI 95% 36-78) months and 66(CI 95% 40-92) months, with a median follow up time of 58 months. The 1-, 2- and 4-year OS was 85%, 85% and 67%, respectively. There were no significant changes in any lung function parameter compared to the preoperative assessment. The FEV(1) showed a trend for improved values after surgery. CONCLUSION: Induction chemotherapy in medically inoperable patients followed by parenchyma-sparing surgery is feasible and yields very promising results.