A phase II trial of dacarbazine, fluorouracil and epirubicin in patients with neuroendocrine tumours. A study by the Italian Trials in Medical Oncology (I.T.M.O.) Group.

Background: Previous experiences in the treatment of neuroendocrine tumours have demonstrated some activity of single agents such as adriamycin, fluorouracil (FU), streptozotocin and dacarbazine (DTIC). Opinions concerning the usefulness of polychemotherapy in carcinoid tumours are discordant, whereas better results have been achieved in other endocrine pancreatic neoplasms. Based on this background, we used multidrug chemotherapy with DTIC, FU and epirubicin in the treatment of different neuroendocrine tumours.

Methods: The study involved 38 pts with progressive and measurable disease. The treatment schedule was FU 250 mg/m2 i.v., epirubicin 25 mg/m2 i.v., and DTIC 200 mg/m2 i.v. on days 1, 2 and 3 every 3 weeks.

Results: The responses achieved by histologic types were carcinoids 2/20, medullary thyroid carcinoma 1/7, neuroendocrine tumours 1/6; and Merkel cell carcinoma 3/5. The median duration of response was 5 months (range 2-11). Stable disease was observed in 13 cases (34%). Out of the 18 cases in progression, 17 had not responded to previous medical treatment. No symptom control was observed in 4 pts with carcinoid syndrome. Treatment toxicity was moderate and included nausea and vomiting, alopecia, leukopenia and mucositis.

Conclusions: Our results document the moderate efficacy of the regimen in all of the histologic types. The major difference in comparison with previous studies was the lower response rate observed in patients with neuroendocrine tumours.