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U.S. National Institutes of Health
Cancer Diagnosis Program Cancer Imaging Program Cancer Therapy Evaluation Program Developmental Therapeutics Program Radiation Research Program Translational Research Program Biometric Research Branch Office of Cancer Complementary and Alternative Medicine

Carboplatin (NSC 241240)

Overview

The utility of platinum compounds in the treatment of cancer was recognized in the 1970s with the development of cisplatin, which was approved by the FDA for use in testicular and ovarian cancer in 1978. Severe toxicities associated with cisplatin motivated efforts to find analogues with improved safety profiles. The greatest success in these early efforts was carboplatin which entered clinical trials in 1982 and was approved by the FDA for use in ovarian cancer in 1989. Carboplatin, like all the platinum compounds, is thought to act primarily as an alkylating agent, causing intrastrand crosslinks in DNA (Rabik and Dolan, Cancer Treat. Rev. 33(1):9-23 (2007)).

Basic Chemistry

  • Chemical Names: Carboplatin, CBDCA, cis-Diammine (1,1-cyclobutanedicarboxylato)platinum(II)
  • Chemical Structure: platinum compound with bidentate cyclobutane dicarboxylate
  • Approximate Solubility:

    Solvent Solubility (mg/mL)
    Water
    > 15
    pH 4 Acetate Buffer
    5 - 10
    pH 9 Carbonate Buffer
    5 - 10
    10% Ethanol/H2O
    5 - 10
    95% Ethanol/H20
    < 1
    0.1 N HCl
    5 - 10
    0.1 N NaOH
    5 - 10
    Methanol
    < 1
    Chloroform
    < 5
    Dimethylsulfoxide
    5
    Acetic Acid
    < 1
    Trifluoroacetic Acid
    < 1

  • Stability
    • Bulk: No decomposition was detected after 30 days at 60 C in the dark (HPLC)
    • Solution: After 48 hours at room temperature an aqueous solution showed < 1% decomposition (HPLC)
  • High Performance Liquid Chromatography
    • Column: Unimetrics LiChrosorb RP -8, 250 4.6 mm i.d.
    • Mobile Phase: Water
    • Flow Rate: 1.0 mL/min
    • Detection: UV at 205 nm
    • Sample Preparation: 0.6 mg/mL in water
    • Internal Standard: (0.11 mg uracil/mL water)
    • Retention Volume: 6.2 mL (NSC - 241240), 5.5 mL (I.S.)

Preclinical Studies

  • in vitro
    • 60 cell screen:
      • 60 cell line screen – carboplatin has limited activity in the 60 cell line screen, with an overall mean GI50 (52 experiments) of 100 micromolar. The most sensitive cell line is HL-60 leukemia line (32 micromolar).

        dose response | mean graph (GI50)

    • in vitro bone marrow toxicity data

      CFUGM inhibitory concentrations (µM)
      Species
      IC50
      IC75
      IC90
      mouse
      250
      500
      800
      dog
      30
      180
      500
      human
      150
      550
      2500
  • in vivo

Clinical Trials

  • Carboplatin was approved by the FDA in 1989 and is in wide use, especially in the treatment of ovarian cancer. There is extensive ongoing work to define the utility of this drug in other cancers, especially in combination with other agents. active trials