New perspectives on an old friend

Optimizing carboplatin for the treatment of solid tumors

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background. Since its clinical introduction in 1981, carboplatin has proved a feasible alternative to cisplatin for the treatment of many solid tumors, especially ovarian cancer. Because the pharmacokinetics and, ultimately, the pharmacodynamics of carboplatin are highly dependent on the status of renal function, fixed dosing based on body surface area has led to carboplatin overdosing or, especially, underdosing. This has resulted in less than optimal treatment results compared with cisplatin in a variety of solid tumor types. Only in the past few years has the optimal dosing method for carboplatin-individualizing the dose (area under the concentration-versus- time curve [AUC]) rather than conventional use of body surface area-been adopted by clinical oncologists. Methods. An extensive review of the oncology literature has been performed to update both carboplatin dosing guidelines as well as its present role in solid tumor chemotherapy. Initial efforts to devise a dosing formula for carboplatin focused on reducing myelotoxicity (especially thrombocytopenia). Subsequently, a simple formula was developed to adjust the carboplatin dose according to renal function. By targeting a carboplatin AUC rather than empirically dosing according to body surface area, doses of carboplatin can be individualized to fall within the drug's therapeutic index. Results. The use of carboplatin dosing guidelines based on renal function has led to optimization of its pharmacodynamic effects both with respect to its safety profile and its ultimate impact on solid tumor response and patient survival. Since carboplatin has little neurotoxicity, it has become the platinum agent of choice in combination with paclitaxel for therapy of previously untreated ovarian cancer. Carboplatin plus etoposide and carboplatin plus paclitaxel have been studied in phase II and III trials, with the latter combination demonstrating improved activity against advanced non-small cell lung cancer. Additional trials in patients with other solid tumors have shown that carboplatin is more cost-effective and less toxic than cisplatin. Conclusions. Dosing based on renal function and a targeted serum AUC, rather than on body surface area, has resulted in the Optimal utilization of carboplatin in cancer chemotherapy. Its predictable toxicity and clinical efficacy equivalent to cisplatin make carboplatin the drug of choice for selected tumor types.

Original languageEnglish (US)
Pages (from-to)15-34
Number of pages20
JournalOncologist
Volume3
Issue number1
StatePublished - 1998

Fingerprint

Carboplatin
Neoplasms
Body Surface Area
Therapeutics
Cisplatin
Area Under Curve
Kidney
Paclitaxel
Ovarian Neoplasms
Guidelines
Drug Therapy
Poisons
Etoposide
Platinum
Non-Small Cell Lung Carcinoma
Thrombocytopenia
Pharmaceutical Preparations

Keywords

  • Carboplatin
  • Cisplatin
  • Etoposide
  • Non-small cell lung cancer
  • Ovarian cancer
  • Paclitaxel
  • Pharmacodynamics
  • Pharmacokinetics
  • Small cell lung cancer
  • Solid tumors

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

New perspectives on an old friend : Optimizing carboplatin for the treatment of solid tumors. / Alberts, David S; Dorr, Robert T.

In: Oncologist, Vol. 3, No. 1, 1998, p. 15-34.

Research output: Contribution to journalArticle

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abstract = "Background. Since its clinical introduction in 1981, carboplatin has proved a feasible alternative to cisplatin for the treatment of many solid tumors, especially ovarian cancer. Because the pharmacokinetics and, ultimately, the pharmacodynamics of carboplatin are highly dependent on the status of renal function, fixed dosing based on body surface area has led to carboplatin overdosing or, especially, underdosing. This has resulted in less than optimal treatment results compared with cisplatin in a variety of solid tumor types. Only in the past few years has the optimal dosing method for carboplatin-individualizing the dose (area under the concentration-versus- time curve [AUC]) rather than conventional use of body surface area-been adopted by clinical oncologists. Methods. An extensive review of the oncology literature has been performed to update both carboplatin dosing guidelines as well as its present role in solid tumor chemotherapy. Initial efforts to devise a dosing formula for carboplatin focused on reducing myelotoxicity (especially thrombocytopenia). Subsequently, a simple formula was developed to adjust the carboplatin dose according to renal function. By targeting a carboplatin AUC rather than empirically dosing according to body surface area, doses of carboplatin can be individualized to fall within the drug's therapeutic index. Results. The use of carboplatin dosing guidelines based on renal function has led to optimization of its pharmacodynamic effects both with respect to its safety profile and its ultimate impact on solid tumor response and patient survival. Since carboplatin has little neurotoxicity, it has become the platinum agent of choice in combination with paclitaxel for therapy of previously untreated ovarian cancer. Carboplatin plus etoposide and carboplatin plus paclitaxel have been studied in phase II and III trials, with the latter combination demonstrating improved activity against advanced non-small cell lung cancer. Additional trials in patients with other solid tumors have shown that carboplatin is more cost-effective and less toxic than cisplatin. Conclusions. Dosing based on renal function and a targeted serum AUC, rather than on body surface area, has resulted in the Optimal utilization of carboplatin in cancer chemotherapy. Its predictable toxicity and clinical efficacy equivalent to cisplatin make carboplatin the drug of choice for selected tumor types.",
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