Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer.
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/microliters (range 36-1600/microliters); 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.
Ben-Baruch
N
N
Medicine Branch, National Cancer Institute, Bethesda, MD 20892.
Denicoff
A M
AM
Goldspiel
B R
BR
O'Shaughnessy
J A
JA
Cowan
K H
KH
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000627:therapeutic use* / Q000031:analogs & derivatives; D003110:Colonic Neoplasms / Q000188:drug therapy*; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; C022121:fazarabine; D001374:Azacitidine