Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucosesolution administered in balloon-occluded hepatic artery: Experimental rationale and clinical pilot study

Citation
N. Isambert et al., Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucosesolution administered in balloon-occluded hepatic artery: Experimental rationale and clinical pilot study, J EXP CL C, 20(2), 2001, pp. 183-188
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
ISSN journal
0392-9078 → ACNP
Volume
20
Issue
2
Year of publication
2001
Pages
183 - 188
Database
ISI
SICI code
0392-9078(200106)20:2<183:HAIOCD>2.0.ZU;2-Y
Abstract
Reduced osmolarity in incubation medium was previously shown to increase in vitro cellular accumulation and cytotoxicity of cisplatin on cancer cells. We confirmed in the present work that cisplatin diluted in an hypotonic 25 g/l glucose solution(124 mOsm) was dramatically more cytotoxic in vitro th an cisplatin diluted in normotonic 9 g/l NaCl (300 mOsm) on the human HT29 colon and MCF7 breast cancer cells. We conducted then a pilot clinical stud y on the administration of cisplatin diluted in hypotonic 25 g/l glucose so lution given through the balloon-occluded hepatic artery for the treatment of liver metastases from colon or breast cancer tumors. Nine patients (5 me n, 4 women;mean age 58, range : 44-71) with confirmed isolated, unresectabl e metastases from colorectal (7) or breast (2) tumors were included in this study and a total of 23 cycles were administered (2.55 per patient; range 1-5) with an average dose of 50 mg cisplatin (range : 12.5-100). Hepatic ar tery dissection due to balloon injury with partial or complete arterial obs truction were encountered in 2 patients. Pain in the liver and epigastric a rea was the main symptom which was constant and intense during the IAH cisp latin injection. Fever > 38 degreesC was observed in 15/23 cycles and incre ase of creatinine in 1/23 cycles. Transient increase of hepatic transaminas es without change in prothrombin time was registered in all patients. Howev er one patient who received the highest dose of 100 mg cisplatin developed a persistent but reversible clinical jaundice and a transient increase in p rothrombin time. One patient achieved a partial response (12 weeks), 7 had stable disease (mean duration: 6 weeks) and one had a progressive disease. Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution and administered through the balloon-occluded hepatic artery is a feasible approach. Total dose of cisplatin in hypotonic glucose solution wi ll not exceed 80 mg by cure in a further phase II study.