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Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis
Authors:H. Mahteme,A. von Heideman,B. Grundmark,B. Tholander,L. På  hlman,B. Glimelius,R. Larsson,W. Graf,P. Nygren
Affiliation:1. Department of Surgical Sciences, University Hospital, Uppsala University, S-75185 Uppsala, Sweden;2. Department of Oncology, Radiology and Clinical Immunology, University Hospital, Uppsala University, S-751 85 Uppsala, Sweden;3. Department of Medical Sciences, University Hospital, Uppsala University, S-751 85 Uppsala, Sweden;4. Department of Oncology and Pathology, Radiumhemmet, Karolinska Institutet, S-171 76 Stockholm, Sweden
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.
Keywords:Peritoneal carcinomatosis   Intraperitoneal chemotherapy   Cytotoxic drug   In vitro
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