title: High-intensity intravenous cyclophosphamide and cisplatin, interim surgical debulking, and intraperitoneal cisplatin in advanced ovarian carcinoma: a pilot trial with ten-year follow-up.
abstract: OBJECTIVE
  This trial was undertaken to study the effect of intensified intravenous cyclophosphamide/cisplatin and interim surgical debulking, followed by intraperitoneal cisplatin on surgically defined complete remission rate and survival in advanced ovarian cancer.
  
  
  METHODS
  Forty patients with stage IIB through IV ovarian cancer were entered and 36 were evaluable for response and survival and approximately 10 years. Following a first laparotomy for diagnosis and debulking, the patients received two cycles, spaced 28 days apart, of intravenous cisplatin 30-40 mg/m2/day with hypertonic saline for 4 to 5 days and cyclophosphamide 200 mg/m2/day for 5 days. A second laparotomy was done to further debulk remaining cancer and to place an intraperitoneal catheter. Four cycles of intraperitoneal cisplatin at 50 or 100 mg/m2 were administered 21 days apart and followed by a third laparotomy to define response and plan any further therapy.
  
  
  RESULTS
  The surgically confirmed complete response rate was 47% and median survival is 68.3 months for this group. Ten of the 17 patients (58.8%) relapsed following complete response at a median of 19.5 months (range, 5-98). Both aggressive chemotherapy and surgery seemed to play a role in inducing this high complete response rate. Traditional prognostic factors, including stage and diameter of largest residual disease, had little apparent effect on likelihood of complete response or survival, whereas tumor grade had a more significant effect on survival. Nadir fever was experienced by 33% of patients but peripheral neuropathy was dose limiting.
  
  
  CONCLUSIONS
  In the context of recent data failing to support any clinical benefit to modest increases in dose escalations of cisplatin or carboplatin, in this trial the high complete response rate suggests that the multimodality approach (i.e., interval surgical debulking and intraperitoneal cisplatin) is worthy of further study. The high relapse rate among complete responders and the unacceptable neurotoxicity also suggest that modifications could improve the results. The use of newer agents and further intensification (substituting carboplatin for cisplatin and the use of paclitaxel) with stem cell support are two examples.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: F
authors.initials: F
authors.lastname: Shapiro
authors.forename: J
authors.initials: J
authors.lastname: Schneider
authors.forename: M
authors.initials: M
authors.lastname: Markman
authors.forename: B S
authors.initials: BS
authors.lastname: Reichman
authors.forename: E
authors.initials: E
authors.lastname: Venkatraman
authors.forename: R
authors.initials: R
authors.lastname: Barakat
authors.forename: L
authors.initials: L
authors.lastname: Almadrones
authors.forename: D
authors.initials: D
authors.lastname: Spriggs
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D010865:Pilot Projects
chemical_list: D003520:Cyclophosphamide; D002945:Cisplatin