Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis

Eur J Surg Oncol. 2008 May;34(5):547-52. doi: 10.1016/j.ejso.2007.05.002. Epub 2007 Jun 18.

Abstract

Aims: To investigate if the pattern of cytotoxic drug sensitivity in vitro in patient samples of peritoneal carcinomatosis (PC) is supportive to the current standardized approach for drug selection for perioperative intraperitoneal chemotherapy (IPC).

Methods: The cytotoxic effect of cisplatin, oxaliplatin, irinotecan, 5-fluorouracil, mitomycin-C, doxorubicin and melphalan was investigated in vitro on tumour cells from 223 patient tumour samples of different PC origins.

Results: Considerable differences in cytotoxic drug sensitivity between tumour types of the PC entity and within each tumour type were observed. Cisplatin showed high cross-resistance with oxaliplatin but low cross-resistance with doxorubicin and irinotecan. No cross-resistance was found between irinotecan and doxorubicin. The dose-response relationships for melphalan and irinotecan in individual samples showed great variability.

Conclusions: The activity in vitro of cytotoxic drugs commonly used in IPC for PC is very heterogeneous. Efforts for individualizing drug selection for PC patients undergoing IPC seem justified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Cisplatin / pharmacology
  • Cytotoxins / pharmacology*
  • Cytotoxins / therapeutic use
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm
  • Female
  • Fluorouracil / pharmacology
  • Humans
  • Irinotecan
  • Male
  • Melphalan / pharmacology
  • Mitomycin / pharmacology
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Perioperative Care
  • Peritoneal Neoplasms / drug therapy*
  • Tumor Cells, Cultured

Substances

  • Cytotoxins
  • Organoplatinum Compounds
  • Oxaliplatin
  • Mitomycin
  • Irinotecan
  • Doxorubicin
  • Cisplatin
  • Melphalan
  • Fluorouracil
  • Camptothecin