Hyperthermia and fibrinolytic therapy do not improve the beneficial effect of radioimmunotherapy following cytoreductive surgery in rats with peritoneal carcinomatosis of colorectal origin.
OBJECTIVE
Cytoreductive surgery (CS) and heated intraperitoneal chemotherapy (HIPEC) are standard treatment for peritoneal carcinomatosis (PC) of colorectal cancer. Previously, we demonstrated that preclinical radioimmunotherapy (RIT) adjuvant to surgery in PC is a good alternative for HIPEC. Now we aimed to improve the effectiveness of RIT by combining it with whole-body hyperthermia (WBH) or fibrinolytic therapy.


METHODS
Rats were inoculated intraperitoneally with colon carcinoma cells. Animals underwent CS, CS + WBH (40 degrees C, 3 hours), CS + RIT (74 MBq 177Lu-labeled MG1), or CS + WBH + RIT. In the second experiment, rats underwent CS, CS + RIT, CS + recombinant tissue plasminogen activator (rtPA, twice daily, 3 days), or CS + RIT + rtPA.


RESULTS
Median survival after CS and CS + WBH was 34 and 37 days. Median survival after CS + RIT or CS + RIT + WBH was 63 and 86 days (p < 0.0003, p < 0.0006 compared to CS + WBH). Median survival after CS and CS + rtPA was 50 and 42 days (p = 0.1). Median survival was 106 days after CS + RIT and 103 days after CS + RIT + rtPA (p < 0.0001 compared to CS + rtPA). No difference was found between CS + RIT and CS + RIT + rtPA (p = 0.83).


CONCLUSIONS
The application of WBH or rtPA in combination with adjuvant RIT after CS for the treatment of PC of colonic was feasible but did not significantly potentiate the efficacy of RIT.
Aarts
Frits
F
Department of Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. F.Aarts@chir.umcn.nl
Hendriks
Thijs
T
Boerman
Otto C
OC
Oyen
Wim J G
WJ
Bleichrodt
Robert P
RP
D000818:Animals; D001835:Body Weight; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D006979:Hyperthermia, Induced; D008297:Male; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000556:secondary* / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D051381:Rats; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D016896:Treatment Outcome
D010959:Tissue Plasminogen Activator