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

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 cisplatin plus doxorubicin than to the duplex drug under PIPAC conditions. The duplex drug suggests itself, notably in cases of platinum resistance, as an alternative or addition to intraperitoneal chemotherapies when platinum-based PIPAC technology is used. Using it with HIPEC technology is not recommended. Higher doses of the duplex drug will enhance growth inhibition, albeit at the cost of a severely reduced difference in chemosensitivity between tumor and normal cells. Our findings provide orientation for PIPAC-based personalized intraperitoneal chemotherapy.

Thermosensitive Exosome–Liposome Hybrid Nanoparticle‐Mediated Chemoimmunotherapy for Improved Treatment of Metastatic Peritoneal Cancer

“…The therapeutic benefit of HIPEC has been limited by various factors, such as inefficient drug penetration and resistance to standard chemotherapy drugs. [8,10,14,47] In this study, we quantified the drug delivery efficiency of HIPEC at the cellular level using single-cell ICP-MS, and found that, compared with small sized tumors, larger tumors are associated with limited drug penetration ( Figure 2). To improve drug delivery to tumors, we developed a novel delivery system through fusion of genetically engineered exosomes and thermosensitive liposomes.…”

Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin or oxaliplatin for peritoneal metastasis from pancreatic adenocarcinoma and cholangiocarcinoma

“…Based on the locoregional administration of pressurized aerosol drugs, it maximizes exposure of peritoneal tumor implants to chemotherapy agents, with favorable pharmacokinetics and biodistribution, as demonstrated in several pre-clinical studies. 14 , 15 …”

Pressurized intraperitoneal aerosol chemotherapy: a review of the introduction of a new surgical technology using the IDEAL framework

“…Overall, the search identified: 23 stage 0 studies; 18 stage 1 studies and two protocol papers for stage 1 studies; 25 stage 2a studies, one protocol paper and five trial registrations (NCT01854255, NCT02735928, NCT03246321, NCT02604784 and NCT03124394) for stage 2a studies; six stage 2b studies and three protocol papers for stage 2b studies; and three protocol papers for stage 3 studies. Fig .…”