title: Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion.
abstract: OBJECTIVE
  To compare the toxicity, pharmacokinetics, and efficacy seen in ovarian cancer patients treated with escalating doses of intraperitoneal (I.P.) interleukin-2 (IL-2) by two different infusion schedules.
  
  
  METHODS
  Forty-five patients were sequentially entered onto a phase I/II study in groups of four at fixed dosage tiers of 6 x 10(4), 6 x 10(5), 6 x 10(6), and 3 x 10(7) IU/m2/d in either of two schedules: (A) intermittent weekly infusions of 24 hours' duration; or (B) alternating continuous 7-day infusions followed by 7-day intervals without therapy. Eligibility criteria included > or = six courses of prior platinum-based chemotherapy and laparotomy-confirmed persistent or recurrent ovarian cancer.
  
  
  RESULTS
  Forty-one eligible patients received I.P. IL-2 and were assessable for toxicity, but six patients were not assessable for response, which left 35 patients assessable for response. Significant locoregional dose-limiting toxicity was seen with the 7-day infusions (including bowel perforation), with 600,000 IU/m2 as the maximum-tolerated dose (MTD), but catheter infection was the only significant complication seen with the 24-hour infusions, for which an MTD was not established. Among 35 assessable patients, there were six laparotomy-confirmed complete responses (CRs) and three partial responses, for an overall response rate of 25.7% (nine of 35). The median survival time of the cohort was 13.7 months and the overall 5-year survival probability was 13.9%. For the nine patients who demonstrated responses (six on the 24-hour infusion and three on the 7-day infusion), the median survival time has not been reached (range, 27 to 90+ months).
  
  
  CONCLUSIONS
  I.P. IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to I.P. IL-2 therapy or other factors that cannot be controlled for in a single-arm study.
authors.affiliation: University of Pittsburgh Cancer Institute, Magee-Womens Hospital, University of Pittsburgh School of Medicine, PA 15213-3180, USA. edwardsb+@pitt.edu
authors.forename: R P
authors.initials: RP
authors.lastname: Edwards
authors.forename: W
authors.initials: W
authors.lastname: Gooding
authors.forename: B C
authors.initials: BC
authors.lastname: Lembersky
authors.forename: K
authors.initials: K
authors.lastname: Colonello
authors.forename: R
authors.initials: R
authors.lastname: Hammond
authors.forename: C
authors.initials: C
authors.lastname: Paradise
authors.forename: C D
authors.initials: CD
authors.lastname: Kowal
authors.forename: A J
authors.initials: AJ
authors.lastname: Kunschner
authors.forename: M
authors.initials: M
authors.lastname: Baldisseri
authors.forename: J M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: R B
authors.initials: RB
authors.lastname: Herberman
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin; D002945:Cisplatin