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Published on: January 25, 2015
Intraperitoneal chemotherapy with melphalan
Abstract:
We administered melphalan by the intraperitoneal route to investigate its toxicity and pharmacokinetics. The drug was instilled with 2 litres of fluid and allowed to dwell in the peritoneal cavity for 4 hours. No local toxicity was detected by clinical examination, laboratory tests, or histologic examination. The intraperitoneal route allowed the dose to be increased to approximately three times the maximum dose tolerated intravenously before drug leaking into the systemic circulation produced dose-limiting myelosuppression. The peak peritoneal concentration averaged 93-fold greater than the plasma concentration, and total drug exposure for the peritoneal cavity averaged 63-fold greater than that for plasma. Tumor regressions were observed in patients with ovarian carcinoma and gastrointestinal adenocarcinomas. This study shows that from the pharmacologic point of view, if any portion of the tumor can be reached by intraperitoneal instillation, then there is a very strong rationale for the administration of melphalan by the intraperitoneal route, rather than the oral or intravenous route, for the treatment of tumors confined to the peritoneal cavity.
Insights
Intraperitoneal melphalan administration shows reduced toxicity and enhanced drug concentration in the peritoneal cavity. This route offers a strong rationale for treating peritoneal tumors, improving drug delivery compared to oral or intravenous methods.
Area of Science:
- Oncology
- Pharmacology
- Clinical Medicine
Background:
- Melphalan is a chemotherapy agent used in cancer treatment.
- Intraperitoneal (IP) drug administration is an alternative delivery method to systemic routes.
- Understanding the pharmacokinetics and toxicity of IP melphalan is crucial for optimizing cancer therapy.
Purpose of the Study:
- To investigate the toxicity and pharmacokinetics of melphalan administered via the intraperitoneal route.
- To compare the efficacy and safety of IP melphalan with traditional administration routes (oral, intravenous).
- To evaluate the potential of IP melphalan for treating tumors confined to the peritoneal cavity.
Main Methods:
- Melphalan was administered intraperitoneally with 2 liters of fluid, dwelling for 4 hours.
- Toxicity was assessed through clinical, laboratory, and histologic examinations.
- Pharmacokinetic parameters, including peak peritoneal and plasma concentrations and total drug exposure, were measured.
- Tumor response was evaluated in patients with ovarian carcinoma and gastrointestinal adenocarcinomas.
Main Results:
- No local toxicity was detected following intraperitoneal melphalan administration.
- The intraperitoneal route allowed for approximately a threefold increase in melphalan dosage compared to intravenous administration before dose-limiting myelosuppression occurred.
- Peak peritoneal melphalan concentration was 93-fold higher, and total peritoneal drug exposure was 63-fold higher than in plasma.
- Tumor regressions were observed in patients with ovarian carcinoma and gastrointestinal adenocarcinomas.
Conclusions:
- Intraperitoneal melphalan demonstrates favorable pharmacokinetics and tolerability for treating peritoneal surface malignancies.
- Higher drug concentrations and exposure in the peritoneal cavity suggest improved local efficacy.
- This route provides a strong rationale for melphalan administration in tumors confined to the peritoneal cavity, outperforming oral or intravenous routes.
