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Last Updated: 04/25/2012

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

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