Deoxyspergualin: Phase I clinical, immunologic and pharmacokinetic study

K. A. Havlin, J. G. Kuhn, J. Koeller, D. H. Boldt, J. B. Craig, T. D. Brown, G. R. Weiss, J. Cagnola, J. Phillips, G. Harman, J. Hardy, D. D. Von Hoff

Research output: Contribution to journalArticle

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Abstract

Deoxyspergualin (DSG) is an analog of the polyamine spergualin with preclinical evidence of activity in murine and human tumor models. This phase I study examined a 120 h continuous infusion schedule in 56 patients with refractory solid tumors at doses ranging from 80 to 2792 mg/m2/day. Dose-limiting toxicity was reversible hypotension and appeared to be associated with plasma levels of DSG > 4 μg/ml. Other dose-dependent effects noted were pruritus and circumoral paresthesias. Myelo-suppression and gastrointestinal toxicities were mild and sporadic. Two patients with refractory head and neck cancer had minor responses. The recommended phase II dose on this schedule is 1800 mg/m2. Additional monitoring to identify immunologic properties included immunophenotyping of peripheral lymphocytes and cytotoxic activity by means of standard 51Cr-release assays. These studies revealed a non-dose-dependent increase in the number of cells expressing T cell antigens predominantly the T suppressor (CD8) phenotype post-treatment. In three patients, a mild increase in LAK activity was noted post-treatment without a consistent relationship to dose or change in cell surface antigens. Pharmacokinetic studies were completed on 26 patients ranging from doses of 80 to 2792 mg/m2. The average plasma concentration ranged from 0.07 to 7 μg/ml. DSG was rapidly cleared from the plasma with a mean terminal half-life of 1.9 h. Mean total body clearance was 25.24 I/h/ m2. Further in vivo immunologic studies should be pursued while the agent is studied in fixed dosage phase II clinical trials.

Original languageEnglish (US)
Pages (from-to)229-236
Number of pages8
JournalAnti-Cancer Drugs
Volume6
Issue number2
StatePublished - 1995
Externally publishedYes

Fingerprint

Pharmacokinetics
Appointments and Schedules
Immunophenotyping
Phase II Clinical Trials
Paresthesia
Viral Tumor Antigens
Polyamines
Pruritus
Surface Antigens
Head and Neck Neoplasms
Hypotension
Half-Life
Neoplasms
Cell Count
T-Lymphocytes
Phenotype
gusperimus
Therapeutics

Keywords

  • Deoxyspergualin
  • Pharmacokinetics
  • Phase I trial

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

Cite this

Havlin, K. A., Kuhn, J. G., Koeller, J., Boldt, D. H., Craig, J. B., Brown, T. D., ... Von Hoff, D. D. (1995). Deoxyspergualin: Phase I clinical, immunologic and pharmacokinetic study. Anti-Cancer Drugs, 6(2), 229-236.

Deoxyspergualin : Phase I clinical, immunologic and pharmacokinetic study. / Havlin, K. A.; Kuhn, J. G.; Koeller, J.; Boldt, D. H.; Craig, J. B.; Brown, T. D.; Weiss, G. R.; Cagnola, J.; Phillips, J.; Harman, G.; Hardy, J.; Von Hoff, D. D.

In: Anti-Cancer Drugs, Vol. 6, No. 2, 1995, p. 229-236.

Research output: Contribution to journalArticle

Havlin, KA, Kuhn, JG, Koeller, J, Boldt, DH, Craig, JB, Brown, TD, Weiss, GR, Cagnola, J, Phillips, J, Harman, G, Hardy, J & Von Hoff, DD 1995, 'Deoxyspergualin: Phase I clinical, immunologic and pharmacokinetic study', Anti-Cancer Drugs, vol. 6, no. 2, pp. 229-236.
Havlin KA, Kuhn JG, Koeller J, Boldt DH, Craig JB, Brown TD et al. Deoxyspergualin: Phase I clinical, immunologic and pharmacokinetic study. Anti-Cancer Drugs. 1995;6(2):229-236.
Havlin, K. A. ; Kuhn, J. G. ; Koeller, J. ; Boldt, D. H. ; Craig, J. B. ; Brown, T. D. ; Weiss, G. R. ; Cagnola, J. ; Phillips, J. ; Harman, G. ; Hardy, J. ; Von Hoff, D. D. / Deoxyspergualin : Phase I clinical, immunologic and pharmacokinetic study. In: Anti-Cancer Drugs. 1995 ; Vol. 6, No. 2. pp. 229-236.
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