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Intraperitoneal cisplatin-based chemotherapy for ovarian carcinoma
S B Howell1, S Kirmani, E F McClay
1Department of Medicine, University of California San Diego, La Jolla 92093.
Seminars in Oncology
|February 1, 1991
Summary
Intraperitoneal cisplatin and etoposide chemotherapy offers improved survival for ovarian cancer patients. This approach enhances drug delivery, overcoming resistance and minimizing toxicity, supporting further clinical trials.
Area of Science:
- Gynecologic Oncology
- Pharmacology
- Clinical Trials
Background:
- Ovarian carcinoma exhibits a steep dose-response curve to cisplatin, yet acquired cellular resistance limits intravenous (IV) chemotherapy efficacy.
- Intraperitoneal (IP) administration significantly increases drug exposure to the peritoneal cavity compared to IV administration.
- Concurrent IV thiosulfate enables safe administration of higher doses of IP cisplatin.
Purpose of the Study:
- To evaluate the efficacy and toxicity of a novel intraperitoneal (IP) chemotherapy regimen in ovarian carcinoma patients.
- To assess the IP cisplatin/etoposide regimen as both salvage and first-line therapy.
- To investigate the impact of tumor burden on treatment outcomes.
Main Methods:
- Two Phase II clinical trials were conducted using an IP regimen of cisplatin (200 mg/m2) and etoposide (350 mg/m2) with IV thiosulfate.
- Trial 1: Salvage therapy for patients with residual disease (<2 cm) after prior cisplatin-based IV chemotherapy.
- Trial 2: First-line therapy for newly diagnosed ovarian carcinoma patients, regardless of post-surgical residual disease size.
Main Results:
- Salvage therapy demonstrated a median survival of 26 months from IP treatment initiation and 51 months from diagnosis.
- First-line therapy has not reached median survival, with a projected 68% survival at 27 months.
- Myelosuppression was the primary toxicity; thiosulfate nearly eliminated nephrotoxicity and neurotoxicity. Tumor size was a key efficacy determinant.
Conclusions:
- The IP cisplatin/etoposide regimen shows promising survival benefits in ovarian carcinoma, both as salvage and first-line treatment.
- Increased drug delivery via the IP route appears to overcome cisplatin resistance and improve patient outcomes.
- Results warrant further investigation in Phase III randomized trials to confirm the efficacy of this treatment approach.