A phase I-II trial of intraperitoneal cisplatin and alpha-interferon in patients with persistent epithelial ovarian cancer.

Abstract

A toxicity, dose, and schedule study of intraperitoneal (ip) cisplatin and alpha-interferon was conducted as a salvage therapy for patients with persistent, advanced epithelial ovarian cancer after primary systemic therapy with cisplatin-combination chemotherapy. Twenty-four patients were entered into this prospective, nonrandomized phase I-II trial conducted at two institutions following a uniform protocol. Cisplatin doses were escalated from 45 to 90 mg/m2, and alpha-interferon doses were escalated from 10 to 50 x 10(6) IU. At protocol entry, 4 (16%) patients had microscopic residual disease at second-look laparotomy, 5 (21%) had minimal residual disease less than 5 mm, 7 (30%) had residual disease 5-20 mm, and 8 (33%) had bulky residual disease greater than 20 mm. Toxicity was acceptable overall. Hematopoietic toxicity included a grade 3 total white cell count in 12% of courses when the cisplatin dose was equal to or greater than 60 mg/m2. Renal toxicity was modest with grade 2 toxicity in 20% of courses with a cisplatin dose greater than 60 mg/m2. Gastrointestinal toxicity, especially nausea and vomiting was seen in most courses; however, it was grade 3 and dose-limiting in greater than 30% of courses with cisplatin 75-90 mg/m2. General malaise, fever, flu-like symptoms, chills, and myalgias were seen in most courses, but it was dose-limiting (grade 3) toxicity in 6-11% of cycles when the dose of interferon was 25-50 x 10(6) IU. There was no grade 4 toxicity. Thus, the maximum tolerated dose (MTD) of the combination is 60 mg/m2 cisplatin and 25 x 10(6) IU interferon. Eighteen patients were evaluable for response, 15 of whom had responded to prior cisplatin therapy and 3 had not. Of the 10 patients evaluable for clinical response, one patient (10%) achieved a complete response (CCR), and one (10%) had a partial response (PCR). The progression free interval (PFI) and survival were 11 months and 19 months, respectively, for the CCR patient, 6 and 11 months, respectively, for the PCR patient, and the mean survival for nonresponders was 8 months. The other 8 patients underwent a reassessment laparotomy: 2 (25%) achieved a complete pathologic response (CPR), and 3 (38%) had a partial pathologic response (PPR). Both pathologic responses were in patients with minimal residual disease less than 5 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

• Authors: J S Berek, C Welander, J C Schink, H Grossberg, F J Montz, J Zigelboim
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 40 Issue 3 Pg. 237-43 (Mar 1991) ISSN: 0090-8258 [Print] United States
• PMID: 2013446 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Type I
• Cisplatin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cisplatin (administration & dosage, adverse effects)
• Drug Evaluation
• Female
• Humans
• Injections, Intraperitoneal
• Interferon Type I (administration & dosage, adverse effects)
• Leukopenia (chemically induced)
• Middle Aged
• Ovarian Neoplasms (drug therapy)