title: Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281.
abstract: OBJECTIVE
  Optimal treatments for metastatic carcinoid tumor remain undefined, and the role of chemotherapy for symptomatic patients with progressive disease is uncertain.
  
  
  METHODS
  Two hundred forty-nine patients with advanced carcinoid tumors were randomized to either doxorubicin with fluorouracil (FU/DOX) or streptozocin with fluorouracil (FU/STZ). Patients crossed over to the dacarbazine (DTIC) treatment after disease progression following first-line treatment (either FU/DOX or FU/STZ), and 73 patients were assigned to one of these three treatments based on their previous treatment or on abnormal baseline cardiac or renal function.
  
  
  RESULTS
  In the randomized group, there was no difference between FU/DOX and FU/STZ in response rates (15.9% v 16%) and progression-free survival (4.5 v 5.3 months). FU/STZ (24.3 months) was superior to FU/DOX (15.7 months; P = .0267) in median survival. The response rate of crossover DTIC treatment was 8.2%, with a median survival of 11.9 months. Hematologic toxicities were the major treatment-related toxicities for both FU/DOX and FU/STZ, and mild to moderate renal toxicity was reported in 40 (34.8%) of 115 patients in the FU/STZ arm.
  
  
  CONCLUSIONS
  Response to all three treatment regimens were modest. FU/STZ improved survival compared with the doxorubicin-based regimen, suggesting that the combination should be considered to be an active regimen of therapy when chemotherapy is judged to be an option for selected patients with carcinoid tumors.
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104-4283, USA. weijing.sun@uphs.upenn.edu
authors.forename: Weijing
authors.initials: W
authors.lastname: Sun
authors.forename: Stuart
authors.initials: S
authors.lastname: Lipsitz
authors.forename: Paul
authors.initials: P
authors.lastname: Catalano
authors.forename: James A
authors.initials: JA
authors.lastname: Mailliard
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D013311:Streptozocin / Q000008:administration & dosage; D016019:Survival Analysis
chemical_list: D013311:Streptozocin; D004317:Doxorubicin; D005472:Fluorouracil