title: Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology group study.
abstract: OBJECTIVE
  To assess progression-free survival (PFS) and overall survival (OS) in patients with suboptimally debulked epithelial ovarian cancer receiving cisplatin (100 mg/m(2)) or 24-hour infusion paclitaxel (200 mg/m(2)) or the combination of paclitaxel (135 mg/m(2)) followed by cisplatin (75 mg/m(2)).
  
  
  METHODS
  After stratification for disease measurability, patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined.
  
  
  RESULTS
  Six hundred fourteen of 648 patients who entered onto the trial were eligible. Monotherapies were discontinued more frequently (cisplatin because of toxicity or patient refusal [17%], and paclitaxel because of progression [20%]) compared with the combination therapy (7% and 6%, respectively). Neutropenia, fever, and alopecia were more severe with paclitaxel-containing regimens; whereas anemia, thrombocytopenia, neurotoxicity, nephrotoxicity, and gastrointestinal toxicity were more severe with cisplatin-containing regimens. The CR/PR rates on paclitaxel monotherapy were significantly lower compared with the cisplatin regimens (42% v 67%, respectively; P <.001). The relative hazard (RH) of first progression or death was significantly greater among those randomized to paclitaxel (RH = 1.41; 95% confidence interval [CI], 1.15 to 1.73; P <.001) when compared with cisplatin; however, RH did not differ significantly between the two cisplatin regimens (RH = 1.06; 95% CI, 0.895 to 1.30). Relative to cisplatin, the death rate on paclitaxel was 15% greater (RH = 1.15; 95% CI, 0. 929 to 1.42), and the death rate on the combination treatment was 1% less (RH = 0.99; 95% CI, 0.795 to 1.23). These differences among treatment groups were not statistically significant (P =.31).
  
  
  CONCLUSIONS
  Cisplatin alone or in combination yielded superior response rates and PFS relative to paclitaxel. However, OS was similar in all three arms, and the combination therapy had a better toxicity profile. Therefore, the combination of cisplatin and paclitaxel remains the preferred initial treatment option.
authors.affiliation: Department of Medicine, Kaplan Cancer Center, New York University, New York, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Muggia
authors.forename: P S
authors.initials: PS
authors.lastname: Braly
authors.forename: M F
authors.initials: MF
authors.lastname: Brady
authors.forename: G
authors.initials: G
authors.lastname: Sutton
authors.forename: T H
authors.initials: TH
authors.lastname: Niemann
authors.forename: S L
authors.initials: SL
authors.lastname: Lentz
authors.forename: R D
authors.initials: RD
authors.lastname: Alvarez
authors.forename: P R
authors.initials: PR
authors.lastname: Kucera
authors.forename: J M
authors.initials: JM
authors.lastname: Small
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D017239:Paclitaxel; D002945:Cisplatin