Carboplatin and paclitaxel, alone and in combination: dose escalation, measurement of renal function, and role of the p53 tumor suppressor gene.
In this pharmacokinetic and dose-escalation study of the carboplatin/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combination, patients were randomly assigned to receive paclitaxel either as a 1-hour or a 3-hour infusion. The 1-hour infusion was feasible, with maximum tolerated doses similar to those previously reported for a 3-hour infusion. Using patients' age, height, plasma creatinine, and plasma creatine kinase provided an improved estimate of the glomerular filtration rate compared with the more traditional creatinine-based formulas according to population analysis of data derived from glomerular filtration rate estimates performed by an isotope method. Studies of the p53 gene sequence of ovarian tumors at diagnosis suggest that p53 mutations are a potent predictor of response to subsequent treatment with carboplatin.
Calvert
A H
AH
Cancer Research Unit, University of Newcastle upon Tyne, Northern Centre for Cancer Treatment, Freeman Hospitals Trust, UK.
Ghokul
S
S
Al-Azraqi
A
A
Wright
J
J
Lind
M
M
Bailey
N
N
Highley
M
M
Siddiqui
N
N
Lunec
J
J
Sinha
D
D
Boddy
A
A
Roberts
T
T
Fenwick
J
J
D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D016158:Genes, p53; D006801:Humans; D007677:Kidney Function Tests; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D017239:Paclitaxel