Correlation of clinical pharmacokinetic parameters of cisplatin with efficacy and toxicity. 1991

B Desoize, and F Marechal, and H Millart, and A Cattan
Institut Jean Godinot, Reims, France.

Twenty-two pharmacokinetic studies were carried out in 11 patients receiving cisplatin (20 mg/m2 per d) associated with etoposide (50 mg/m2 per d), as 5-day continuous infusions, every 4 weeks. Blood was withdrawn at 8:30 am from day 1-5. Within 15 min after taking the blood, an aliquot of plasma was filtered for the ultrafilterable platinum (UP) assay. Total platinum (TP) and UP were assayed by flameless atomic absorption. The plasma concentrations and AUC0-120 h of TP were correlated with those of UP (P less than 0.05 to P less than 0.001). TP concentrations increased significantly during the infusion and with each successive course, whereas the increase of plasma concentration of UP during and between courses was not statistically significant. The responders had significantly higher levels of TP (AUC, concentrations) in the first and second courses than the non-responders. No renal toxicity was observed, nevertheless, the AUC0-120 h of TP and UP were positively correlated with the serum creatinine (P less than 0.05). The digestive intolerance (grade 1-3) was significantly correlated with TP concentrations and AUC0-120 h. There was no statistical difference in UP concentrations either between responders and non-responders in any course, nor between toxic and non-toxic courses. Since etoposide was concomitantly administered, we can formulate the conclusion as follows: no "objective" response was observed in the patients with low TP plasma concentrations and AUC0-120 h.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004066 Digestive System Diseases Diseases in any part of the GASTROINTESTINAL TRACT or the accessory organs (LIVER; BILIARY TRACT; PANCREAS). Digestive System Disorders,Hepatobiliary Diseases,Hepatobiliary Disorders,Digestive System Disease,Digestive System Disorder,Hepatobiliary Disease,Hepatobiliary Disorder,System Disorders, Digestive
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014462 Ultrafiltration The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in DIALYSIS separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as HEMOFILTRATION or HEMODIAFILTRATION (if combined with HEMODIALYSIS).

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