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Related Experiment Videos

2-Chlorodeoxyadenosine dose escalation in nonhematologic malignancies

A Saven1, H Kawasaki, C J Carrera

  • 1Department of Radiology, Ida M. and Cecil H. Green Cancer Center, Scripps Clinic and Research Foundation, La Jolla, CA 92037.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|April 1, 1993
PubMed
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The maximum-tolerated dose (MTD) of 2-chlorodeoxyadenosine (2-CdA) for solid tumors is 0.1 mg/kg/d. While 2-CdA showed activity in malignant astrocytomas, deoxycytidine kinase levels did not predict response.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • 2-chlorodeoxyadenosine (2-CdA) is an antineoplastic agent.
  • Dose-escalation studies are crucial for determining safe and effective cancer therapies.
  • Understanding the toxicity profile and MTD of novel agents is essential for clinical application.

Purpose of the Study:

  • To determine the maximum-tolerated dose (MTD) of 2-chlorodeoxyadenosine (2-CdA) in patients with solid tumors.
  • To define the toxicity profile of 2-CdA at higher doses.
  • To explore the relationship between deoxycytidine kinase (dCK) levels and 2-CdA efficacy.

Main Methods:

  • A dose-escalation study involving 21 patients with malignant astrocytoma, metastatic melanoma, or metastatic hypernephroma.
  • Administration of 2-CdA via continuous intravenous infusion at doses of 0.1, 0.15, or 0.2 mg/kg/d for 7 days every 28 days.

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  • Measurement of 2-CdA levels and deoxycytidine kinase (dCK) in tumor tissue.

    • Main Results:

    • The MTD was determined to be 0.1 mg/kg/d, with myelotoxicity observed at higher doses.
    • Two of seven patients with astrocytomas achieved partial responses, with a median duration of 8 months.
    • 2-CdA penetrated the blood-brain barrier; dCK levels did not correlate with tumor response.

    Conclusions:

    • The MTD of 2-CdA for nonhematologic malignancies is 0.1 mg/kg/d, consistent with that for hematologic malignancies.
    • No clinical correlation was found between dCK expression and response to 2-CdA.
    • Observed responses in malignant astrocytoma warrant further investigation in Phase II studies.