Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma

Gemcitabine has modest activity in the treatment of advanced pancreatic can cer and is a potent radiosensitizer. We conducted a Phase I trial to determ ine the maximum tolerated dose of weekly gemcitabine delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinom a of the pancreatic head and to assess the treatment-related toxic effects associated with such a regimen. Eighteen patients with pathologically prove n, locally advanced adenocarcinoma of the pancreatic head were enrolled in this study. Patients received seven weekly doses of gemcitabine with 3000 c Gy of external beam radiation therapy delivered during the first 2 weeks of therapy. Six patients received gemcitabine at 350 mg/m(2)/week, nine at 40 0 mg/m(2)/week, and three at 500 mg/m(2)/week. Grade 3-4 hematological toxi city was observed in over half the patients treated. Nonhematological toxic ities were significant and included fatigue, anorexia, nausea, vomiting, an d dehydration. Forty-four % of the patients required admission to the hospi tal for management of nausea/vomiting and dehydration. The risk of hospital ization appeared to be dose-related; all of the three patients treated at 5 00 mg/m(2)/week required hospital admission during treatment. Seventeen pat ients were evaluated for response, and eight patients (47%) had evidence of a local anticancer effect. Four of these eight patients (24%) had a partia l response to therapy. The median survival for the entire group was 6 month s. The I-year survival rate for patients with an objective response to ther apy was 66%. The clinical responses observed in this group of patients sugg est gemcitabine is a clinically relevant radiosensitizer in patients with p ancreatic adenocarcinoma. However, the toxic effects are significant, sugge sting that until dose and scheduling issues are explored further, concomita nt administration of gemcitabine and radiation therapy should still be cons idered investigational.