Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis.
OBJECTIVE
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.
Mahteme
H
H
Department of Surgical Sciences, University Hospital, Uppsala University, S-75185 Uppsala, Sweden.
von Heideman
A
A
Grundmark
B
B
Tholander
B
B
Påhlman
L
L
Glimelius
B
B
Larsson
R
R
Graf
W
W
Nygren
P
P
D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D003603:Cytotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008558:Melphalan / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D019990:Perioperative Care; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D003603:Cytotoxins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D016685:Mitomycin; D000077146:Irinotecan; D004317:Doxorubicin; D002945:Cisplatin; D008558:Melphalan; D005472:Fluorouracil; D002166:Camptothecin