title: Combination chemotherapy with cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP) for squamous cancers of the upper aerodigestive tract.
abstract: Based on the demonstration of in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP), we designed a Phase II trial of Ara-C plus CDDP for patients with advanced squamous cancers of the head and neck and esophagus. Sixteen patients were treated on a unique schedule of continuous-infusion Ara-C, 30 mg/m2/day over 72 h, plus CDDP, 30 mg/m2/day at hours 12, 36, and 60 of the Ara-C infusion. The objective response rate was 38% (95% confidence limits 14-62%), with two patients achieving complete clinical and radiographic response (9 and 27+ months duration) and four partial responses (median duration 4 months, range 1-7 months). There was no CDDP-related nephro- or neurotoxicities, but a flu-like syndrome of anorexia and asthenia was common. Myelosuppression was the dose-limiting toxicity, necessitating Ara-C dose adjustments in 11 cycles of therapy and leading to fatal sepsis in one patient. We conclude that the activity of this combination, though comparable to that of other CDDP-containing regimens, offers no significant therapeutic advantage, and given the excessive hematologic toxicity, should not be investigated further.
authors.affiliation: Department of Medical Oncology, City of Hope National Medical Center, Duarte, California 91010.
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: J
authors.initials: J
authors.lastname: Doroshow
authors.forename: L
authors.initials: L
authors.lastname: Leong
authors.forename: S
authors.initials: S
authors.lastname: Akman
authors.forename: B I
authors.initials: BI
authors.lastname: Carr
authors.forename: O
authors.initials: O
authors.lastname: Odujinrin
authors.forename: B
authors.initials: B
authors.lastname: Flanagan
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004341:Drug Evaluation; D004357:Drug Synergism; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D003561:Cytarabine; D002945:Cisplatin