Combined radiochemotherapy of locally advanced unresectable pancreatic adenocarcinoma with mitomycin C plus 24-hour continuous infusional gemcitabine

Background: In locally advanced pancreatic cancer, the combination of chemo therapy with radiotherapy is gaining increasing importance; although, in vi ew of the reported long-term results of several contemporary trials, furthe r improvements are certainly warranted, The aim of the present study was to evaluate the effectiveness and safety of a combined-treatment modality con sisting of systemic chemotherapy with 24-h continuous infusional gemcitabin e and mitomycin C, plus external beam radiotherapy in patients with localiz ed unresectable adenocarcinoma of the pancreas, Methods and Materials: Systemic chemotherapy consisted of mitomycin C 8 mg/ m(2) given as i.v. bolus injection on day 1 and gemcitabine administered as a 24-h continous infusion once weekly for 3 of 4 weeks, The starting dose of gemcitabine was 100 mg/m(2) and dose levels were escalated in consecutiv e cohorts of 3-6 patients to 130 and 160 mg/m(2), utilizing an escalating-d ose Phase I trial design, Radiation therapy using megavolt irradiation (tot al dose, 45 Gy, 1.8 Gy/day) of 6 MV photons or greater with a 3- or 4-field technique was delivered concurrently for 5-6 weeks. Results: Between January 1997 and August 1998, a total of 15 patients were enrolled in this trial, all of whom were assessable for toxicity, response, and survival, The dose-limiting toxicities at the 160 mg/m(2) gemcitabine level were myelosuppression, specifically neutropenia +/- thrombocytopenia, and gastrointestinal symptoms, including stomatitis, vomiting, and diarrhe a, Only 1 partial response was observed (7%), and disease was stabilized in 10 additional patients (67%), The median time to progression was 5.5 month s (range, 2-12 months). Whereas all patients developed distant metastases, locoregional failure occurred in only 3, The median survival time was 8.3 m onths (range, 2.5 to 22.0+ months), and the I-year survival rate was 13.3%. Conclusion: The MTD of gemcitabine when given as prolonged infusion in comb ination with mitomycin C and radiation therapy was 130 mg/m(2)/week. Therap eutic results suggest that combined chemoradiation with this regimen is fea sible and effective for local control of pancreatic cancer, but essentially ineffective in counteracting metastatic tumor growth. (C) 2001 Elsevier Sc ience Inc.