title: Edatrexate improves the antitumor effects of cyclophosphamide and cisplatin against non-small cell lung cancer.
abstract: The authors treated 32 patients with Stage IIIB or IV non-small cell lung cancer (NSCLC) with an outpatient regimen of edatrexate (10-ethyl-10-deaza-aminopterin) (10-EdAM) on days 1 and 8, cyclophosphamide on day 1, and cisplatin on day 1, repeated every 3 weeks with dose modification. The 22 men and 10 women (median age, 57 years of age) had no prior chemotherapy and a Zubrod performance status less than or equal to 2. A schedule with initial doses of 80 mg/m2, 800 mg/m2, and 80 mg/m2, respectively, yielded a 47% major response rate with two complete responses (95% confidence interval [CI], 25% to 70%), but it also yielded significant stomatitis and myelosuppression. A schedule with reduced starting doses (70 mg/m2, 700 mg/m2, and 70 mg/m2) was better tolerated, but dropped the major response rate to 27% with no complete responses (95% CI, 11% to 52%). Median survival time was 39 weeks for all 30 evaluable patients without a significant difference between the treatment groups (which were comparable in patient characteristics). Major response, however, was associated with longer survival time than minor response or no change (P = 0.024) or progressive disease (P = 0.001) (median survival times, 55, 39, and 27 weeks, respectively). When the doses delivered were compared, patients treated with the reduced dose schedule received less mean 10-EdAM per course (P = 0.01), although the doses of cyclophosphamide and cisplatin were comparable to the original dose schedule for the second course and thereafter. These results suggest that this three-drug regimen may have synergistic antitumor effects, with a steep dose-response relationship, particularly with 10-EdAM. With amelioration of the dose-limiting stomatitis of 10-EdAM, it seems possible to maximize the antitumor effects of this regimen.
authors.affiliation: Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.forename: H I
authors.initials: HI
authors.lastname: Libshitz
authors.forename: F V
authors.initials: FV
authors.lastname: Fossella
authors.forename: W K
authors.initials: WK
authors.lastname: Murphy
authors.forename: A C
authors.initials: AC
authors.lastname: Pang
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
authors.forename: D M
authors.initials: DM
authors.lastname: Shin
authors.forename: I W
authors.initials: IW
authors.lastname: Dimery
authors.forename: B S
authors.initials: BS
authors.lastname: Glisson
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
mesh_terms: D000328:Adult; D000368:Aged; D000630:Aminopterin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide; C040210:edatrexate; D000630:Aminopterin