title: Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then-cisplatin in patients with previously untreated advanced epithelial ovarian cancer.
abstract: OBJECTIVE
  To examine the activity and safety of two sequentially scheduled chemotherapy regimens comprising four cycles of paclitaxel (pctx) 200 mg/m2/3 hours then four cycles ofcisplatin (cisDDP) 100 mg/m2, and vice versa, in patients with previously untreated advanced ovarian cancer.
  
  
  METHODS
  Between January 1994 and February 1996, we recruited 30 patients to the pctx-then-cisDDP regimen and 29 to cisDDP-then-pctx, in parallel phase II trials.
  
  
  RESULTS
  Both regimens were predictably active with responses seen in 22 of 30 patients (OR 74%; CR 27%, PR 47%) treated with pctx-then-cisDDP, as against 13 of 21 patients (OR 62%; CR 38%, PR 24%) treated with cisDDP-then-pctx. The OR rate to four cycles of pctx (induction) was 43%, with 27% disease progression; the OR to four cycles of cisDDP (induction) was 57%, with 5% progression. However, progression rates across both induction and consolidation phases were 16% (pctx-then-cisDDP) and 29% (cisDDP-then-pctx). Both regimens were unacceptably neurotoxic. II patients suffering grade 3 sensory neurotoxicity (5 on pctx-then-cisDDP, 6 on cisDDP-then-pctx) and 20 having grade 3 deafness (9 on pctx- then-cisDDP, 11 on cisDDP-then-pctx).
  
  
  CONCLUSIONS
  The activity of these sequential regimens justifies their further development using the less neurotoxic platinum analogue carboplatin, perhaps combining paclitaxel with other platinum non-cross resistant drugs.
authors.affiliation: CRC Trials Unit, Institute for Cancer Studies, University of Birmingham, UK. PooleCJ@aol.com
authors.forename: C J
authors.initials: CJ
authors.lastname: Poole
authors.forename: T
authors.initials: T
authors.lastname: Perren
authors.forename: A
authors.initials: A
authors.lastname: Burton
authors.forename: S D
authors.initials: SD
authors.lastname: Jordan
authors.forename: A H
authors.initials: AH
authors.lastname: Jenkins
authors.forename: J J
authors.initials: JJ
authors.lastname: Mould
authors.forename: D A
authors.initials: DA
authors.lastname: Spooner
authors.forename: D
authors.initials: D
authors.lastname: Luesley
authors.forename: K K
authors.initials: KK
authors.lastname: Chan
authors.forename: S
authors.initials: S
authors.lastname: Sturman
authors.forename: H M
authors.initials: HM
authors.lastname: Earl
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D002945:Cisplatin