title: Phase II trial of fenretinide [N-(4-hydroxyphenyl) retinamide] in myelodysplasia: possible retinoid-induced disease acceleration.
abstract: To determine the activity of fenretinide in patients with myelodysplastic syndromes, 15 patients were treated (300 mg/d starting dose, escalated to 400 mg/d) for a 12-week course. No responses were observed in 14 evaluable patients. Exacerbation of thrombocytopenia occurred in one patient with chronic myelomonocytic leukemia, who succumbed to an intracerebral hemorrhage after 3 weeks of treatment. Two patients with long-standing stable sideroblastic anemia experienced interval leukemic progression. In one patient, clinical features of chronic myelomonocytic leukemia appeared, characterized by a striking rise in peripheral monocyte count (0.49 x 10(9)/l to 10.8 x 10(9)/l) and hepatosplenomegaly, which resolved promptly after cessation of treatment. The second patient experienced evolution into acute myelomonocytic leukemia with cytogenetic progression. The drug was well tolerated with no patient having to discontinue treatment because of toxicity. We conclude that fenretinide lacks clinical efficacy in the treatment of myelodysplasia and in some patients may enhance leukemic progression.
authors.affiliation: Section of Hematology/Oncology, Veterans Administration Medical Centers, Tucson, AZ 85723.
authors.forename: H S
authors.initials: HS
authors.lastname: Garewal
authors.forename: A
authors.initials: A
authors.lastname: List
authors.forename: F
authors.initials: F
authors.lastname: Meyskens
authors.forename: A
authors.initials: A
authors.lastname: Buzaid
authors.forename: B
authors.initials: B
authors.lastname: Greenberg
authors.forename: S
authors.initials: S
authors.lastname: Katakkar
mesh_terms: D000208:Acute Disease; D000368:Aged; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D004341:Drug Evaluation; D017313:Fenretinide; D006801:Humans; D007938:Leukemia / Q000139:chemically induced; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced; D014212:Tretinoin / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D017313:Fenretinide; D014212:Tretinoin