A phase I/II study of recombinant interferon alpha 2a and hydroxyurea for chronic myelocytic leukemia.
Nine previously untreated patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were treated with recombinant interferon alpha 2a (rIFN-alpha 2a) and hydroxyurea. Patients received 6 X 10(6) U rIFN-alpha 2a daily for the first week and 3 X 10(6) U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3 X 10(6) U rIFN-alpha 2a 3 times a week. Simultaneously, hydroxyurea was given, starting at a dose of 40 mg/kg on day one. The maintenance dosage was adjusted to the white blood cell count. Two patients responded with complete hematological remissions but without cytogenetic and molecular-genetic improvements. Seven patients responded with partial hematological remissions. Response to therapy was rapid; normal white blood cell counts were reached after a median of 12 days. The doses of rIFN-alpha 2a and hydroxyurea needed to keep the leucocyte count in the normal range were low (3 X 10(6) U rIFN-alpha 2a 3 times per week, 0.5-1.5 g hydroxyurea/day). Acute toxicity of the combination therapy consisted of fever (9 of 9 patients), flulike symptoms (7 of 9 patients), pruritus and/or rash (3 of 9 patients) and evidence of a tumor cell lysis syndrome (1 of 9 patients). The side effects were not dose-limiting. Combination therapy with rIFN-alpha 2a and hydroxyurea for CML is well tolerated and allows quick and effective hematological control of the disease.
Anger
B
B
Division of Internal Medicine III, University of Ulm, Federal Republic of Germany.
Porzsolt
F
F
Leichtle
R
R
Heinze
B
B
Bartram
C
C
Heimpel
H
H
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004341:Drug Evaluation; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics / Q000628:therapy*; D007958:Leukocyte Count; D010677:Philadelphia Chromosome; D010976:Platelet Count; D011994:Recombinant Proteins
D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D007770:L-Lactate Dehydrogenase; D006918:Hydroxyurea