title: A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study.
abstract: OBJECTIVE
  The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population.
  
  
  METHODS
  Patients were randomized to receive ifosfamide (1.5 g/m(2)/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m(2)/day) times 5 days. No patient had received previous chemotherapy.
  
  
  RESULTS
  Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for "other" metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test).
  
  
  CONCLUSIONS
  The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination.
authors.affiliation: Department of Gynecologic Oncology, Indiana University Medical School, Indianapolis, Indiana, 46202, USA.
authors.forename: G
authors.initials: G
authors.lastname: Sutton
authors.forename: V L
authors.initials: VL
authors.lastname: Brunetto
authors.forename: L
authors.initials: L
authors.lastname: Kilgore
authors.forename: J T
authors.initials: JT
authors.lastname: Soper
authors.forename: R
authors.initials: R
authors.lastname: McGehee
authors.forename: G
authors.initials: G
authors.lastname: Olt
authors.forename: S S
authors.initials: SS
authors.lastname: Lentz
authors.forename: J
authors.initials: J
authors.lastname: Sorosky
authors.forename: J G
authors.initials: JG
authors.lastname: Hsiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002296:Carcinosarcoma / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D014594:Uterine Neoplasms / Q000188:drug therapy*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002945:Cisplatin; D007069:Ifosfamide