title: Tirapazamine plus cisplatin in advanced or recurrent carcinoma of the uterine cervix: a Southwest Oncology Group study.
abstract: The objective of this study was to determine objective response and overall survival (OS) and progression-free survival (PFS) following cisplatin plus tirapazamine treatment in eligible consenting patients with metastatic or recurrent squamous or adenosquamous carcinoma of the cervix. Treatment consisted of intravenous tirapazamine, 260 mg/m(2), followed by cisplatin, 75 mg/m(2), every 21 days for six cycles. Of 56 registered cases, 52 were evaluable for toxicity. There were six grade 4 toxicities (anemia [three], dyspnea [one], neutropenia/granulocytopenia [one], and dehydration [one]). Fifty-three patients were evaluable for response, OS, and PFS. The 6-month OS rate was 56.6% (95% CI 43.3-69.9%). The objective response rate was 32.1% (4 complete [2 confirmed and 2 unconfirmed] and 13 partial [8 confirmed and 5 unconfirmed]). Higher response rates (16/34 [47.1%] vs 1/19 [5.3%], P= 0.0018) were observed in patients who had not previously received radiation-sensitizing chemotherapy, as were OS and PFS (13.9 vs 4.0 months, P < 0.0001; 5.3 vs 1.8 months, P= 0.01). The OS was considered too low to warrant further testing in this disease setting. Despite this, tirapazamine plus cisplatin was active in patients who had not received cisplatin previously. Prior use of radiosensitizing chemotherapy impacted response and survival significantly and should be considered in future clinical trials.
authors.affiliation: Department of Obstetrics and Gynecology, 1 University of New Mexico Health Sciences Center, MSC 10 5580, Albuquerque, NM 87131-5286, USA. hsmith@salud.unm.edu
authors.forename: H O
authors.initials: HO
authors.lastname: Smith
authors.forename: C S
authors.initials: CS
authors.lastname: Jiang
authors.forename: G R
authors.initials: GR
authors.lastname: Weiss
authors.forename: A V
authors.initials: AV
authors.lastname: Hallum
authors.forename: P Y
authors.initials: PY
authors.lastname: Liu
authors.forename: W R
authors.initials: WR
authors.lastname: Robinson
authors.forename: P C
authors.initials: PC
authors.lastname: Cheng
authors.forename: S A
authors.initials: SA
authors.lastname: Scudder
authors.forename: M
authors.initials: M
authors.lastname: Markman
authors.forename: D S
authors.initials: DS
authors.lastname: Alberts
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D016879:Salvage Therapy; D016019:Survival Analysis; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin