Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer

Noa Ben-Baruch, Andrea M. Denicoff, Barry R. Goldspiel, Joyce A. O'Shaughnessy, Kenneth H Cowan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Fazarabine (Arabinofuranosyl-5-azacytosine) is a synthetic pyrimidine nucleoside which combines the arabinose sugar of cytosine arabinoside with the triazine base of 5-azacytidine. It has demonstrated activity against a variety of human solid tumor xenografts including colon, lung and breast cancers. Eighteen patients with refractory metastatic colon cancer were enrolled in a phase II trial of fazarabine. The drug was administered as a 72 hr continuous infusion every 3-4 weeks; the starting dose was 2 mg/m2/hr as established in a previous phase I study. The major toxicity was neutropenia, as predicted from the phase I study. The median time to nadir for cycle 1 was 20 days, with a median granulocyte count of 437/μl (range 36-1600/μl); recovery was within 2-4 days, with only one incidence of fever and neutropenia in 42 cycles. Especially noted for their absence were thrombocytopenia, nausea, vomiting and stomatitis. No objective clinical responses were seen; one patient had stabilization of rapidly growing liver metastases for a period of 7 months. In view of fazarabine's narrow range of toxicities, future dose intensification trials utilizing fazarabine in combination with hematopoietic growth factors are worthy of consideration.

Original languageEnglish (US)
Pages (from-to)71-74
Number of pages4
JournalInvestigational New Drugs
Volume11
Issue number1
DOIs
StatePublished - Feb 1 1993

Fingerprint

fazarabine
Colonic Neoplasms
Neutropenia
Pyrimidine Nucleosides
Azacitidine
Triazines
Stomatitis
Arabinose
Cytarabine
Granulocytes
Heterografts
Thrombocytopenia
Nausea
Vomiting
Lung Neoplasms
Intercellular Signaling Peptides and Proteins
Fever
Breast Neoplasms
Neoplasm Metastasis
Liver

Keywords

  • colon cancer
  • fazarabine (arabinofuranosyl-5-azacytosine ara-AC, NSC 281272)
  • phase II

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer. / Ben-Baruch, Noa; Denicoff, Andrea M.; Goldspiel, Barry R.; O'Shaughnessy, Joyce A.; Cowan, Kenneth H.

In: Investigational New Drugs, Vol. 11, No. 1, 01.02.1993, p. 71-74.

Research output: Contribution to journalArticle

Ben-Baruch, Noa ; Denicoff, Andrea M. ; Goldspiel, Barry R. ; O'Shaughnessy, Joyce A. ; Cowan, Kenneth H. / Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer. In: Investigational New Drugs. 1993 ; Vol. 11, No. 1. pp. 71-74.
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