Ex vivo assessment of chemotherapy sensitivity of colorectal cancer peritoneal metastases.

Abstract

Patients with peritoneal metastasis from colorectal cancer (PMCRC) may have a chance of cure when treated with cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC)1–5. Choice of chemotherapy for HIPEC has been based on knowledge of its systemic effects, pharmacokinetics, technical feasibility, hyperthermic efficacy enhancement, and tolerance6–8. Selection of cancer drugs for treatment based on phenotypical assessment of patient cancer cell drug sensitivity ex vivo is one approach to personalized cancer treatment. One technique for this is the fluorometric microculture cytotoxicity assay (FMCA) that has been used in drug development and for the development of personalized cancer medicine9–16. This study investigated whether ex vivo assessment of drug sensitivity by the FMCA provides predictive information in terms of peritoneal recurrence-free survival (PRFS) and overall survival (OS) in patients treated with CRS and HIPEC for isolated PMCRC. The patient cohort for this study was from a prospectively maintained institutional database at the Uppsala University Hospital, a tertiary care unit for PMCRC in Uppsala, Sweden. Patients with PMCRC treated with CRS and HIPEC have been registered since 2003. Ex vivo drug sensitivity testing using the FMCA started in April 2007. Thus, consecutive patients treated with CRS and HIPEC for PMCRC from April 2007 to October 2018 were considered for providing data for this report. Patients underwent HIPEC with either single-drug oxaliplatin, mitomycin C, or irinotecan, or a combination of oxaliplatin and irinotecan. HIPEC was performed in an open manner according to the coliseum method. Single-drug oxaliplatin was dosed at 350–460 mg/m2, and oxaliplatin and irinotecan combined at 360 mg/m2 for both drugs. These treatments lasted for 30 min. Mitomycin C was dosed at 35 mg/m2 divided into three injections with 50 per cent given at time 0, 25 per cent at 30 min, and 25 per cent at 60 min from the start of HIPEC for a total of 90 min. Follow-up data on PRFS and OS were collected for the final analysis. The Uppsala University ethical committee approved the study (Dnr 2007/237 for tumour sampling and ex vivo assessment of drug activity, and Dnr 2013/203 for clinical data collection).