Glucose effects in an ovarian cancer protocol of exceptional activity.
A French multidrug protocol for stage III ovarian cancer has achieved 77% pathologic complete response, 100% total response, and 81% actuarial 4-year survival. Our analysis indicates that these rates exceed typical with very high statistical significance. Yet neither the drugs, the combined intravenous and intraperitoneal mode of delivery, nor potential bias in the predominantly suboptimal patient population appear to explain the protocol's exceptional results. Here we propose that the atypical administration of intraperitoneal glucose prior to drugs underlies the unusual activity of this protocol. We review studies demonstrating that high-dose glucose has pronounced effects on cancer cells, most notably, substantial potentiation of certain antineoplastic agents. We consider possible mechanisms of such glucose potentiation, including hypothesized osmotic effects that would be especially strong under intraperitoneal administration. We conclude that the French ovarian cancer protocol may represent a significant advance and that glucose potentiation may be more widely applicable as an adjunct to cancer chemotherapy.
Scheim
D E
DE
George Washington University Medical Center, Washington DC 20037.
Lin
J Y
JY
D000206:Actuarial Analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D005947:Glucose / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008875:Middle Aged; D008954:Models, Biological; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012086:Reoperation; D013885:Thiosulfates / Q000627:therapeutic use
D013885:Thiosulfates; D003561:Cytarabine; D001761:Bleomycin; C017717:sodium thiosulfate; D005947:Glucose; D002945:Cisplatin; D005472:Fluorouracil; D007069:Ifosfamide