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Unexpected high incidence of severe toxicities associated with alpha interferon, low-dose cytosine arabinoside and all-trans retinoic acid in patients with chronic myelogenous leukemia.
- Source :
-
Leukemia & lymphoma [Leuk Lymphoma] 1999 Nov; Vol. 35 (5-6), pp. 483-9. - Publication Year :
- 1999
-
Abstract
- Preclinical data have shown that all-trans retinoic acid (ATRA) with interferon-alpha (IFN-alpha) can exert significant suppressive effects on Philadelphia-chromosome (Ph)-positive cells. The aim of this study combining IFN-alpha, low-dose cytosine arabinoside (ara-C) and ATRA was to increase the proportion of patients achieving a major cytogenetic response, in comparison with a group of 140 patients previously treated with IFN-alpha plus low-dose ara-C. Forty three patients with Ph-positive CML in early chronic phase were treated with IFN-alpha 5 MU/m2 s.c. daily, low-dose ara-C 10 mg s.c. daily and ATRA 45 mg/m2 orally daily, for 7 consecutive days every other week. Overall, 76% of patients achieved a complete hematologic response (CHR). A cytogenetic response was in observed 59% (major in 38% and complete in 17%). Compared with patients treated with IFN-alpha and low-dose ara-C, those receiving additional ATRA had a lower CHR rate (p. 014), but other response rates were similar. Severe toxicities were common with the triple regimen (64%), mostly related to ATRA therapy. Two patients experienced pseudotumor cerebri; two patients had leukocytosis during the week on ATRA treatment, decreasing during the week off (one suffered a severe asthma-like reaction followed by pulmonary edema, resembling ATRA syndrome). Six patients had other unusual side-effects: aseptic necrosis of the hip (1 patient), ataxic syndrome (1 patient), paranoid syndrome (2 patients), syncopal episodes (1 patient), pure red cell aplasia (1 patient). In conclusion the results of IFN-alpha and low-dose ara-C combined with ATRA in patients with early CML-chronic phase were disappointing, due to excessive toxicity. Whether different ATRA dose schedules may result in fewer side-effects and improve hematologic and cytogenetic response remains to be determined.
- Subjects :
- Adult
Aged
Antimetabolites, Antineoplastic administration & dosage
Antimetabolites, Antineoplastic adverse effects
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Ataxia chemically induced
Combined Modality Therapy adverse effects
Cytarabine administration & dosage
Drug Administration Schedule
Female
Femur Head Necrosis chemically induced
Humans
Immunologic Factors administration & dosage
Immunologic Factors adverse effects
Interferon-alpha administration & dosage
Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality
Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy
Life Tables
Male
Middle Aged
Paranoid Disorders chemically induced
Pilot Projects
Pulmonary Edema chemically induced
Red-Cell Aplasia, Pure chemically induced
Remission Induction
Survival Analysis
Syncope chemically induced
Treatment Outcome
Tretinoin administration & dosage
Antineoplastic Combined Chemotherapy Protocols adverse effects
Cytarabine adverse effects
Interferon-alpha adverse effects
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Leukocytosis chemically induced
Pseudotumor Cerebri chemically induced
Tretinoin adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1042-8194
- Volume :
- 35
- Issue :
- 5-6
- Database :
- MEDLINE
- Journal :
- Leukemia & lymphoma
- Publication Type :
- Academic Journal
- Accession number :
- 10609785
- Full Text :
- https://doi.org/10.1080/10428199909169612