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In vitro pharmalogic rationale for intraperitoneal regional chemotherapy
K H Link1, U Butzer, J Pillasch
1Department of General Surgery, University Hospital of Ulm, Germany.
Cancer Treatment and Research
|January 1, 1996
Summary
This study evaluated drug effectiveness for intraperitoneal regional chemotherapy (IPRC). In vitro tests on cell lines and tumor samples identified optimal drug concentrations and exposure times, improving drug selection for IPRC.
Area of Science:
- Oncology
- Pharmacology
- Experimental Therapeutics
Background:
- Intraperitoneal regional chemotherapy (IPRC) requires precise drug selection and administration.
- Understanding drug concentration-response and time-dependency is crucial for optimizing IPRC efficacy.
- Existing data on drug behavior in IPRC settings is limited, necessitating preclinical evaluation.
Purpose of the Study:
- To support the concept of intraperitoneal regional chemotherapy (IPRC).
- To improve drug selection rationale for IPRC through in vitro studies.
- To define concentration-response and time-dependency of cytotoxic drugs.
Main Methods:
- In vitro studies using human colorectal carcinoma cell lines (HT29, NMG 64/84) and individual tumor cell suspensions.
- Evaluation of drug cytotoxicity, concentration-response, and time-dependency for various chemotherapeutic agents.
- In vitro phase II studies using the human tumor colony assay (HTCA) with solid tumor biopsies.
Main Results:
- All tested drugs exhibited time- and concentration-dependent cytotoxic activity against cell lines.
- Human tumor colony assay (HTCA) revealed varying cytotoxic concentration responses among drugs and individual tumor biopsies.
- An overall increase in in vitro response by a factor of 2.1 +/- 0.7 was observed when comparing response rates at different concentrations.
Conclusions:
- In vitro studies successfully qualified various drugs for IPRC.
- Optimal drug exposure times for IPRC were suggested based on cytotoxicity data.
- These findings supported the successful clinical application of NOV in an IPRC study.