Prospective Validation of a Pharmacologically Based Dosing Scheme for the cis-Diamminedichloroplatinum(ll) Analogue Diamminecyclobutanedicarboxylatoplatinum

Merrill J. Egorin, Eve A. Olman, Alan Forrest, David A. Van Echo, Margaret Y. Whitacre, Joseph Aisner

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

Abstract

We previously correlated both renal function and thrombocytopenia, the dose limiting toxicity of carboplatin, with the plasma pharmacokinetics of carboplatin. From these correlations, we developed equations to calculate carboplatin dosage for any patient based on that patient's creatinine clearance, body surface area, pretreatment platelet count, desired platelet nadir, and status of prior chemotherapy. We prospectively applied these equations in 44 courses of carboplatin given to 24 patients. There were 13 males and 11 females with median age 53 (range, 33-77), median Kamofsky performance status 80 (range, 50-100), and creatinine clearance 32 to 118 ml/min. Ten patients had creatinine clearances less than 60 ml/min. Precision of the equations used for dose calculation was evaluable in 38 courses administered to 23 patients. In 23 courses of carboplatin administered to 12 patients without extensive prior chemotherapy, the observed change in platelets = 1.04 x predicted change 48,000 (r = 0.96). In the 15 courses of carboplatin administered to 11 heavily pretreated patients, the observed change in platelets = 1.13 x predicted change + 6,600 (r = 0.97). For the overall combined population, the observed change in platelets = 0.96 x predicted change - 7,000 (r = 0.94). These relationships which nearly define the line of identity (observed = expected) validate our initial observations. Only 2 patients developed WBC <2,000, but 12 patients developed hematocrit <29% and 8 required RBC transfusions. Fifteen patients had nausea and vomiting >grade 2. There were no other nonhematological toxicities observed. In view of continuing documentation of the antitumor activity of carboplatin, these equations allow safe and rational drug dosing of patients with potentially platinum-responsive tumors but with renal function too poor to receive cispiatin. Among the 9 patients in this study evaluable for response, there was 1 partial response in a patient with malignant melanoma and 1 objective response (<partial response) in a patient with adenocarcinoma of the cervix.

Original languageEnglish (US)
Pages (from-to)6502-6506
Number of pages5
JournalCancer Research
Volume45
StatePublished - Dec 1 1985
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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