Marimastat as first-line therapy for patients with unresectable pancreaticcancer: A randomized trial

Purpose: The prognosis for unresectable pancreatic cancer remains dismal (1 -year survival rate, < 10%; 5-year survival rate, < 5%). Recent advances in conventional chemotherapy and novel molecular treatment strategies warrant investigation. This, the largest randomized study in pancreatic cancer per formed to date, compares marimastat, the first of a new class Of agents, wi th gemcitabine. Patients and Methods: Four hundred fourteen patients with unresectable panc reatic cancer were randomized to receive marimastat 5, 10, or 25 mg bid or gemcitabine 1,000 mg/m(2). The primary end point was survival. Progression- free survival, patient benefit, and safety were also assessed. Results: There was no significant difference in survival between 5, 10, or 25 mg of marimastat and gemcitabine (P = .19). Median survival times were 1 11, 105, 125, and 167 days, respectively, and 1-year survival rates were 14 %, 14%, 20%, and 19%, respectively. There was a significant difference in s urvival rates between patients treated with gemcitabine and marimastat 5 an d 10 mg (P < .003). Both agents were well tolerated, although grade 3 or 4 toxicities were reported in 22% and 12% of the gemcitabine- and marimastat- treated patients, respectively. The major toxicity of marimastat was muscul oskeletal (44% of marimastat patients, compared with 12% of gemcitabine pat ients; musculoskeletal toxicity was severe in only 8% of marimastat patient s). Conclusion: The results of this study provide evidence of a dose response f or marimastat in patients with advanced pancreatic cancer. The 1-year survi val rate for patients receiving marimastat 25 mg was similar to that of pat ients receiving gemcitabine. in view of the manageable tolerability of mari mastat and its ease of administration, further studies are warranted.