Rationale supporting the use of vasoconstrictors for intraperitoneal chemotherapy with platinum derivatives.
By decreasing drug drainage through the peritoneal and tumoral vascular networks, epinephrine increases the penetration of cisplatin and oxaliplatin into the metastatic peritoneal tumor nodules. This improved drug penetration increases their antitumor efficacy, allowing the cure of millimetric-sized peritoneal tumor nodules that could not be obtained with cisplatin or oxaliplatin used alone. However, limited drug diffusion into supramillimetric nodules did not result in curing advanced peritoneal carcinomatosis, unless complete resection of macroscopic localized tumor nodules is performed before intraperitoneal chemotherapy. In our opinion, the intraperitoneal epinephrine-cisplatin combination should be clinically assessed in completely or almost completely surgically resected peritoneal carcinomatosis with the objective of preventing recurrent tumors. Due to its reduced toxicity, repeated courses of intraperitoneal oxaliplatin associated with epinephrine could be an interesting alternative to cisplatin for the unresectable disease.
Chauffert
Bruno
B
Unité INSERM 517, Faculty of Medicine, 7, Boulevard Jeanne d'Arc, BP 87900, 21079, Dijon, France. bchauffert@dijon.fnclcc.fr
Favoulet
Patrick
P
Polycarpe
Emmanuel
E
Duvillard
Christian
C
Beltramo
Jean-Luc
JL
Bichat
Francis
F
Rat
Patrick
P
Genne
Philippe
P
Benoit
Laurent
L
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001682:Biological Availability; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004357:Drug Synergism; D004837:Epinephrine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin; D004837:Epinephrine