Cancer Chemotherapy and Pharmacology

, Volume 10, Issue 2, pp 125–128 | Cite as

Clinical pharmacology of arabinofuranosyladenine in combination with deoxycoformycin

  • Pierre P. Major
  • Ram P. Agarwal
  • Donald W. Kufe
Original Articles Deoxycoformycin ara-A

Summary

We have administered five courses of arabinofuranosyladenine (ara-A) and deoxycoformycin (DCF) to two patients and have studied the effects of DCF on the pharmacokinetics of ara-A. Ara-A was given by IV infusion over 3 h at a dose of 300 mg/m2/day for 3 days on the first two courses of treatment for each patient. One patient received a third course at a dose of 300 mg/m2/day every 12 h for 3 days. During the first course of treatment, patients received DCF (10 mg/m2) 60 min prior to the ara-A infusion on days 2 and 3 only. However, during subsequent courses, DCF was administered on each of the 3 days. On day 1 of the first course of treatment ara-A was not detectable in the plasma, while ara-hypoxanthine (ara-hyp) reached levels of up to 12.0 μg/ml. On day 2, DCF pretreatment resulted in detectable ara-A levels and decreased ara-hyp. On day 3, the levels of ara-A increased further and ara-hyp was no longer detectable. On subsequent courses, the administration of DCF on each of the 3 days of treatment resulted in detectable ara-A levels on day 1, with progressive increases on days 2 and 3. During the second course of treatment, increases in the excretion half-life of ara-A were noted during the 3-day treatment schedule, with values increasing from 258.2 min to 546 min and from 77.3 min to 219 min for patients I and II, respectively. Peak CSF ara-A levels were approximately one-third of peak plasma levels. No toxicity was encountered in patients treated at these doses of ara-A and DCF. Abrupt declines in peripheral blast counts were observed in each patient.

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Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Pierre P. Major
    • 1
  • Ram P. Agarwal
    • 2
  • Donald W. Kufe
    • 1
  1. 1.Division of Medicine, Sidney Farber Cancer InstituteHarvard Medical SchoolBoston
  2. 2.Section of Medical Oncology, The Evans Memorial Department of Clinical Research, Department of PharmacologyBoston University Medical CenterBostonUSA

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