Abstract
BackgroundThe optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis (PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC from colorectal cancer (CRC).MethodsPC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset.ResultsMesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients.ConclusionsDrug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. In the CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.
Highlights
The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis (PC) is poorly defined
We investigated ex vivo the activity of standard cytotoxic drugs in IPC on tumor cells derived from patients with various types of PC using an ex vivo model reflecting clinical drug activity
Drug sensitivity ex vivo Samples from colorectal cancer (CRC), appendix cancer, and pseudomyxoma peritonei (PMP) generally had higher 50% inhibitory concentration (IC50) values compared to the other groups with the exception of 5-FU (Figure 1)
Summary
The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis (PC) is poorly defined. Aggressive cytoreductive surgery (CRS) followed by intraperitoneal chemotherapy (IPC), may produce prolonged long-term survival and even cure [1,2,3,4,5]. The most recent development in the management of PC is the intraoperative use of hyperthermic intraperitoneal chemotherapy (HIPEC) [6]. The individual therapeutic impact of cytoreductive surgery and IPC, respectively, has not been sufficiently. The IPC protocols in use do not take into consideration possible differences in drug sensitivity in the different tumor types or differences in tumor cell sensitivity between individual patients. A more differential approach to drug selection for the IPC in PC might provide more benefit from this part of the treatment of PC
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