1-arabinofuranosylcytosine-5--stearylphosphate and Leukemia

We attempted a combination chemotherapy with cytarabine ocfosfate (SPAC) and etoposide for myelodysplastic syndrome (MDS), and acute non-lymphocytic leukemia developing after a prior history of MDS (MDS/ANLL). SPAC and etoposide were administered orally at the dose of 200 mg/day and 25 mg/day for 14 days, as standard regimen. Two cases complete remission (CR), 4 of partial remission (PR) were obtained among 9 patients. The plasma concentration of cytarabine (Ara-C) reached a plateau at around 4.5 ng/ml during the treatment period from the 7th to the 14th day, and it was detectable with a gradual decrease until the 28th day in spite of the last administration of SPAC on the 14th day. It is suggested that this combination chemotherapy is useful against MDS, MDS/ANLL and other resistant leukemia, especially in elderly patients who can not be treated by intensive combination chemotherapy.

Topics: Acute Disease; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleotides; Cytidine Monophosphate; Drug Administration Schedule; Etoposide; Female; Humans; Leukemia; Male; Middle Aged

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Arabinonucleotides; Cytidine Monophosphate; Drug Administration Schedule; Drug Evaluation; Female; Humans; Japan; Leukemia; Male; Middle Aged; Myelodysplastic Syndromes; Nausea; Remission Induction; Vomiting

A 58-year-old female was diagnosed as myelodysplastic syndrome (MDS) [refractory anemia with excess of blasts (RAEB)]. Although melphalan was administered, no response was obtained in the peripheral blood. Sixteen months after diagnosis, she developed RAEB in transformation (RAEB-t), and then overt leukemia. White blood cell (WBC) count elevated to 28,600/microliters with 34% of blasts. She was administered cytarabine ocfosfate (200 mg-->300 mg/day) orally, resulting in decrease of WBC count and blasts in peripheral blood. The drug has been given for 11 months, and her hematological data have now remained stable in RAEB. Cytarabine ocfosfate might be a useful drug for the treatment of high risk MDS such as RAEB and RAEB-t.

Topics: Acute Disease; Administration, Oral; Anemia, Refractory, with Excess of Blasts; Antineoplastic Agents; Arabinonucleotides; Cytidine Monophosphate; Female; Humans; Leukemia; Middle Aged

A 73-year-old man was admitted to our hospital with pancytopenia in December, 1992. The data of his peripheral blood were as follows: WBC 1,100/microliters (stab 9.0, seg 11.5, eosin 3.5, mono 1.0, lymph 75.0), RBC 176 x 10(4)/microliters, Hb 6.6 g/dl, platelet 4.6 x 10(4)/microliters. Bone Marrow was hypocellular (cell count 1.4 x 10(4)/microliters) and consisted of 30% blasts (peroxidase positive). He was diagnosed as having hypoplastic leukemia. Oral administration of cytarabine ocfosfate (50 mg/day) was begun from the 5th of January, 1993. The dose of cytarabine ocfosfate was increased to 100 mg/day since the 13th of January, 1993, and he was discharged from the hospital on the 23rd of January, 1993. Since then, he has been treated with cytarabine ocfosfate alone in the outpatient clinic. Pancytopenia began to improve in one month, and the data on the 7th of May, 1993 were as follows: WBC 3,500/microliters (stab 2.0, seg 37.5, eosin 1.5, baso 1.0, mono 16.5, lymph 41.5), RBC 249 x 10(4)/microliters, Hb 10.4 g/dl, platelet 15.4 x 10(4)/microliters. Bone marrow became normocellular (cell count 22.0 x 10(4)/microliters) and blasts decreased to 3.0%, and complete remission was confirmed. There were no adverse effects.

Topics: Administration, Oral; Aged; Arabinonucleotides; Blood Cell Count; Bone Marrow Cells; Cytidine Monophosphate; Humans; Leukemia; Male; Remission Induction

Topics: Adult; Aged; Antineoplastic Agents; Arabinonucleotides; Chronic Disease; Cytidine Monophosphate; Drug Evaluation; Female; Humans; Leukemia; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Remission Induction

YNK01 (a daily oral dose of 450 mg) was administered for 22 days to a 58-year-old-female with Ph1-positive acute unclassified leukemia. Leukemia cells were negative for peroxidase and esterase, but were positive for CD19, CD13, CD34, CD9, HAL-DR, CD25, and TdT. Complete remission was obtained and continued for at least a month. The main side effects noted were diarrhea and melena. The administration of YNK01 resulted in plasma ara C levels that ranged between 15.4 to 23.0 ng/ml, which appear to be nearly equivalent to dose achieved during continuous IV infusion of a low dose (20 mg/m2/day) of ara C.

Topics: Acute Disease; Administration, Oral; Antineoplastic Agents; Arabinonucleotides; Cytarabine; Cytidine Monophosphate; Drug Administration Schedule; Female; Humans; Leukemia; Middle Aged; Prodrugs; Remission Induction

Topics: Acute Disease; Antineoplastic Agents; Arabinonucleotides; Cytidine Monophosphate; Cytosine Nucleotides; Drug Evaluation; Humans; Leukemia; Myelodysplastic Syndromes