Chemosensitivity of various peritoneal cancer cell lines to HIPEC and PIPAC: comparison of an experimental duplex drug to standard drug regimens in vitro

Investigational New Drugs
Jürgen WeinreichTimm C Schott

Abstract

We performed an in-vitro study testing the chemosensitivity of peritoneal cancer cell lines (SW620, HCT116, MKN45, 23,132/87, OAW42) to various cytostatic drug regimens. A duplex drug, characterized by reversible linking of the antimetabolites 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), was compared to oxaliplatin or to cisplatin plus doxorubicin. The experiments were designed to reflect the conditions of intraperitoneal chemotherapy. CASY® (Cell Analysis System) technology was used to compare the impact of incubation temperature/duration and drug concentration on the viability of the cancer cell lines versus normal human dermal fibroblasts. Two incubation scenarios were explored: (i) hyperthermic intraperitoneal chemotherapy (HIPEC) with 1 h of incubation at 42 °C, and (ii) pressurized intraperitoneal aerosol chemotherapy (PIPAC) with several successive incubations at 37 °C. Under HIPEC conditions, oxaliplatin induced a potent temperature-dependent growth inhibition of colon cancer cells not seen with the duplex drug. Under PIPAC conditions, the duplex drug achieved the same growth inhibition at a fraction of the dose level required with oxaliplatin. Gastric and ovarian cancer cells were more sensitive to...Continue Reading

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