PHASE-II STUDY OF FAZARABINE (NSC-281272) IN PATIENTS WITH METASTATICCOLON-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, lun g and breast cancers. Eighteen patients with refractory metastatic col on cancer were enrolled in a phase II trial of fazarabine. The drug wa s administered as a 72 hr continuous infusion every 3-4 weeks; the sta rting 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 stud y. The median time to nadir for cycle 1 was 20 days, with a median gra nulocyte count of 437/mul (range 36-1600/mul); 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, vomi ting and stomatitis. No objective clinical responses were seen; one pa tient had stabilization of rapidly growing liver metastases for a peri od of 7 months. In view of fazarabine's narrow range of toxicities, fu ture dose intensification trials utilizing fazarabine in combination w ith hematopoietic growth factors are worthy of consideration.