All trans retinoic acid with low dose cytosine arabinoside in the treatment of myelodysplastic syndrome.
The demonstration of synergistic interaction between differentiation inducing agents and DNA synthesis inhibitors suggests that these two groups act by two different mechanisms. We prospectively studied the response rate, response duration, survival, and toxicity in 10 patients with myelodysplastic syndrome (MDS) treated with all trans retinoic acid (ATRA) and low dose cytosine arabinoside (ara-C). These patients diagnosed between October 1993 and May 1995 were treated with ATRA (45 mg/M2/day) for 90 days followed by 90 mg/M2 on alternate day till Day 275; together with Ara-C (10 mg/m2) subcutaneously twice daily for 21 days for a total of 6 cycles. These patients were analyzed for response after 3 cycles of LD Ara-C and at the time of completion of therapy. Toxicity was recorded at the end of each cycle of Ara-C. There were 6 male and 4 female patients in the age range of 24 to 76 years. The morphological diagnosis was chronic myelomonocytic leukemia in 2, refractory anemia with excess blasts in 4 and refractory anemia with excess blasts in transformation in 4. Only 1 patient achieved a complete remission and 1 patient achieved a partial response. Four patients had progressive disease on treatment. One patient died of neutropenic sepsis and 1 of resistant thrombocytopenia and intracranial hemorrhage while on treatment. One patient refused further treatment after a minor clinical response and in 1 patient treatment was stopped due to toxicity. This data in a pilot study with a limited number of patient suggests that ATRA in combination with Ara-C has little effect in MDS.
Nair
R
R
Department of Medical Oncology, Tata Memorial Hospital, Parel Mumbai, India.
Nair
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CN
Advani
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SH
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D000970:Antineoplastic Agents; D003561:Cytarabine; D014212:Tretinoin