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Lookup NU author(s): Professor Alan Calvert, Professor Herbie Newell
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This paper reviews the role of pharmacokinetic methods in the clinical use of carboplatin. Published data establish that pretreatment renal function is the most significant determinant of carboplatin pharmacokinetics. Evidence suggests that the area under the plasma concentration versus time curve (AUC) correlates well with hematologic toxicity. Published data also suggest that a relationship exists between the AUC and therapeutic outcome in testicular teratoma and in ovarian cancer, although in the latter case the data are not conclusive. It is suggested that pharmacokinetically based dosing schemes may be advantageous and that randomized trials should be performed to test this hypothesis. In some clinical situations where dose prediction is not feasible, a simple therapeutic drug-monitoring strategy may prove useful. Since the toxicities of carboplatin are mainly hematologic, it has been possible to study the use of high-dose carboplatin with various forms of hematologic support. Carboplatin doses have been increased fourfold to sixfold and high response rates have been reported in ovarian cancer. An overall therapeutic advantage for this strategy has not yet been demonstrated in a randomized setting. Published data on ovarian cancer cell lines suggest that the range of sensitivities encountered is very large (30- to 100-fold). If the range of sensitivities found in vivo is equally large, then a clinical dose escalation of 10- to 100-fold may be necessary to produce a curative therapy for this disease. The investigation of the use of hematopoietic growth factors in association with carboplatin has just begun. Early data suggest that some support of the WBC count may be achieved, but the toxicities of granulocyte-macrophage colony-stimulating factor have themselves been a problem. Our own studies will attempt to achieve a substantial escalation in the administered AUC of carboplatin by increasing the frequency of carboplatin dosing, while administering granulocyte colony-stimulating factor and platelet support.
Author(s): Calvert AH, Newell DR, Gore ME
Publication type: Article
Publication status: Published
Journal: Seminars in Oncology
Year: 1992
Volume: 19
Issue: 1 supplement 2
Pages: 155-163
Print publication date: 01/02/1992
ISSN (print): 0093-7754
ISSN (electronic): 1532-8708
PubMed id: 1411627
