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

Abstract

In locally advanced pancreatic cancer, the combination of chemotherapy with radiotherapy is gaining increasing importance; although, in view of the reported long-term results of several contemporary trials, further improvements are certainly warranted. The aim of the present study was to evaluate the effectiveness and safety of a combined-treatment modality consisting of systemic chemotherapy with 24-h continuous infusional gemcitabine and mitomycin C, plus external beam radiotherapy in patients with localized unresectable adenocarcinoma of the pancreas. Systemic chemotherapy consisted of mitomycin C 8 mg/m2 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/m2 and dose levels were escalated in consecutive cohorts of 3-6 patients to 130 and 160 mg/m2, utilizing an escalating-dose Phase I trial design. Radiation therapy using megavolt irradiation (total 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. 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/m2 gemcitabine level were myelosuppression, specifically neutropenia +/- thrombocytopenia, and gastrointestinal symptoms, including stomatitis, vomiting, and diarrhea. Only 1 partial response was observed (7%), and disease was stabilized in 10 additional patients (67%). The median time to progression was 5.5 months (range, 2-12 months). Whereas all patients developed distant metastases, locoregional failure occurred in only 3. The median survival time was 8.3 months (range, 2.5 to 22.0+ months), and the 1-year survival rate was 13.3%. The MTD of gemcitabine when given as prolonged infusion in combination with mitomycin C and radiation therapy was 130 mg/m2/week. Therapeutic results suggest that combined chemoradiation with this regimen is feasible and effective for local control of pancreatic cancer, but essentially ineffective in counteracting metastatic tumor growth.