Interferon alpha plus intermittent oral Ara-C ocfosfate (YNK-01) in chronic myeloid leukemia primarily resistant or with minimal cytogenetic response to interferon.
OBJECTIVE
Subcutaneous Ara-C plus interferon (IFN) produces more cytogenetic responses than IFN in chronic myeloid leukemia (CML) but a greater toxicity. The objective of this study was to determine the efficacy and tolerance of IFN plus oral Ara-C ocfosfate (YNK-01) in IFN-resistant CML patients.


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), with progressive escalation if tolerated, in addition to IFN. Cytogenetic assessment was performed thereafter.


RESULTS
Of the first 7 patients, 5 had severe hematologic and 5 moderate gastrointestinal toxicity; IFN was reduced in 6, YNK-01 in 5, and treatment discontinued in 2; hematologic response was achieved in 2 of the 5 evaluable 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 Ara-C were reduced in 2 patients and treatment discontinued in 2 due to progression or toxicity; the other 2 achieved a minor cytogenetic response, progressing in one to a major response after 6 more cycles. In 8 patients the starting Ara-C 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 cytogenetic response.


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.
Cervantes
F
F
Hematology Department, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. fcervan@clinic.ub.es
Sureda
A
A
Hernández-Boluda
J C
JC
Martino
R
R
Brunet
S
S
Borrego
D
D
Antich
J L
JL
Montserrat
E
E
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D001088:Arabinonucleotides / Q000008:administration & dosage; D003568:Cytidine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020732:Cytogenetic Analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
D001088:Arabinonucleotides; D016898:Interferon-alpha; C061162:1-arabinofuranosylcytosine-5'-stearylphosphate; D003568:Cytidine Monophosphate