Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer

Background. Gemcitabine and radiotherapy are a potent combination. A clinic al assessment of the therapeutic ratio for locally advanced pancreatic canc er patients has not yet been reported. Aim of Study. To assess the toxicity, survival, and pattern of failure of l ocally advanced pancreatic cancer patients treated with concurrent gemcitab ine-based chemoradiation. Patients and Methods. Between the dates of December 1996 and August 2000 51 patients with locally advanced unresectable adenocarcinoma of the pancreas were treated with concurrent gemcitabine and radiotherapy at MDACC. Patien ts received 250-500 mg/m(2) of gemcitabine weekly x7 over 30 min and 30-33 Gy in 10-11 fractions over two weeks to the primary tumor and regional lymp hatics. Severe toxicity was defined as admission > 5 d, mucosal ulceration, > 3 dose deletions of gemcitabine or toxicity resulting in surgical interv ention or that resulted in death. Results. The median survival was 11 mo. Overall, 37 of 51 patients had obje ctive evidence of local progression. The actuarial rate of local progressio n rate at 9 mo was 70%. The 9-mo distant metastasis rate was 52%. Tumors gr eater than or equal to 10 cm(2) had worse local control, distant control, a nd overall survival. Six patients underwent pancreaticoduodenectomy after t herapy. After review of the imaging, only four of these patients had minima l arterial involvement, one was incorrectly staged, and one had initial inf lammatory change on CT that resolved. Twelve of 51 (24%) patients suffered severe acute toxicity, and 17 of 51 (33%) patients were admitted for suppor tive care. Conclusion. Concurrent gemcitabine and radiotherapy can be a very difficult combination to administer safely. Our results do not suggest a prolongatio n of median survival for patients with localized pancreatic cancer treated with this therapy. It is possible that gemcitabine-based chemoradiation con tributes to the margin-negative resectability of a small number of patients with minimal arterial involvement, but this benefit is obscured by the fre quent toxicity encountered in most patients. Locally advanced pancreatic ca ncer patients should continue to be enrolled on prospective studies investi gating novel combinations of cytotoxic and/or biologic agents with concurre nt radiotherapy.