Interferon alpha plus intermittent oral Ara-C ocfosfate (YNK-01) in chronic myeloid leukemia primarily resistant or with minimal cytogenetic responseto interferon

Background and Objectives. Subcutaneous Ara-C plus interferon (IFN) produce s more cytogenetic responses than IFN in chronic myeloid leukemia (CML) but a greater toxicity. The objective of this study was to determine the effic acy and tolerance of IFN plus oral Ara-C ocfosfate (YNK-01) in IFN-resistan t CML patients. Design and Methods. A phase II pilot study was conducted in 19 CML patients primarily resistant or with minimal cytogenetic response to IFN. Patients were scheduled to receive 6 monthly 14-day cycles of YNK-01 (500 mg/day), w ith progressive escalation if tolerated, in addition to IFN. Cytogenetic as sessment was performed thereafter. Results, Of the first 7 patients, 5 had severe hematologic and 5 moderate g astrointestinal toxicity; IFN was reduced in 6, YNK-01 in 5, and treatment discontinued in 2; hematologic response was achieved in 2 of the 5 evaluabl e patients. In the following 4 patients the Ara-C was reduced to 300 mg: 2 had severe hematologic and 2 moderate gastrointestinal toxicity; IFN and Ar a-C were reduced in 2 patients and treatment discontinued in 2 due to progr ession or toxicity; the other 2 achieved a minor cytogenetic response, prog ressing in one to a major response after 6 more cycles. In 8 patients the s tarting AraC dose was 200 mg: 5 had moderate-severe hematologic and 5 mild gastrointestinal toxicity; IFN was reduced in 5, Ara-C in 1, and treatment discontinued in 1; Ara-C was increased in 7 cases; hematologic response was obtained in 4 patients, 2 of whom attained a minor and 1 a major cytogenet ic response. Interpretation and Conclusions. These results provide background for future studies aimed at ascertaining the role of oral Ara-C combined with IFN or STI571 in newly diagnosed CML. (C) 2001, Ferrata Storti Foundation.