title: FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer.
abstract: OBJECTIVE
  The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer.
  
  
  METHODS
  Sixty patients were entered onto the trial, 30 receiving EAP and 30 FAMTX. All patients had measurable or assessable tumor masses. Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis.
  
  
  RESULTS
  Response rates were similar between the two arms (FAMTX, 33% [95% confidence interval (CI), 16% to 50%]; EAP, 20% [95% Cl, 6% to 34%]). Three FAMTX and no EAP patients had complete remissions. The median survival for the two arms were similar (EAP, 6.1 months; FAMTX, 7.3 months). At 1 year, 7% of EAP and 17% of FAMTX patients were alive. EAP caused significantly more myelosuppression (leukopenia, P = .002; anemia, P = .03; thrombocytopenia, P = .0001) than did FAMTX. EAP also resulted in significantly longer hospitalizations per study month (8 v 5 days). Four EAP patients died of lethal toxicity, whereas no FAMTX patients died of treatment-related causes (P = .04).
  
  
  CONCLUSIONS
  FAMTX is at least as active as EAP and is significantly less toxic. Although both regimens remain investigational, the toxicities of FAMTX are more manageable. Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway.
authors.affiliation: Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: D
authors.initials: D
authors.lastname: Kelsen
authors.forename: O T
authors.initials: OT
authors.lastname: Atiq
authors.forename: L
authors.initials: L
authors.lastname: Saltz
authors.forename: D
authors.initials: D
authors.lastname: Niedzwiecki
authors.forename: D
authors.initials: D
authors.lastname: Ginn
authors.forename: D
authors.initials: D
authors.lastname: Chapman
authors.forename: R
authors.initials: R
authors.lastname: Heelan
authors.forename: C
authors.initials: C
authors.lastname: Lightdale
authors.forename: V
authors.initials: V
authors.lastname: Vinciguerra
authors.forename: M
authors.initials: M
authors.lastname: Brennan
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate