ORLANDO--Combination therapy utilizing interferon alfa-2b(Drug information on interferon alfa-2b) (Intron A) and cytarabine(Drug information on cytarabine) is associated with improved cytogenetic response and survival over interferon alone in patients with chronic myelogenous leukemia (CML), a French study, presented at the 38th Annual Meeting of the American Society of Hematology (ASH), has shown.
François Guilhot, MD, head of the Department of Hematology and Clinical Oncology, Centre Hospitalier Universitaire de Poitiers, presented the data for the French CML study group.
The 5-year randomized study included 810 patients with Philadelphia chromosome-positive (Ph+) CML from 70 French centers. All patients were given hydroxyurea (Hydrea), 50 mg/kg daily, and interferon at a starting dose of 5 × 106 IU/m²/day. Hydroxyurea was discontinued once a complete hematologic remission (CHR) was achieved.
Of 646 evaluable patients, 324 received the interferon alone regimen and 322 received interferon plus monthly courses of cytarabine, 20 mg/m²/day, for 10 days. Endpoints included CHR at 6 months, major cytogenetic response (suppression of Ph+ cells to less than 35%) at 12 months, and overall survival.
At 6 months, a CHR of 67% was achieved in the combination therapy group, compared with 54% in the interferon alone group (P = .002); time to response was similar in both study arms. At 12 months, a major cytogenetic response was obtained in 96 (39%) of 248 patients receiving cytarabine, compared with 55 (22%) of 249 patients who did not receive cytarabine (P less than .001).
Survival was significantly improved in the interferon plus cytarabine group. The 3-year survival rate was 88% in the combination group, compared with 76% in the interferon alone group.
When adjusted for variables of white blood cell count and hemoglobin level or Sokal score, overall survival remained significantly improved in the interferon plus cytarabine group. In both groups, patients who achieved a major cytogenetic response had longer survival.
During the first 12 months, the mean daily dose of interferon was 5 × 106 IU/m²/day in both groups, and the median number of courses of cytarabine was 7, with a median daily dose of 31 mg. The median duration of treatment with interferon plus cytarabine was 35 months, and with interferon alone, 28 months.
Treatment was discontinued due to major side effects in 94 patients in both the combination group and in the group receiving interferon alone. Major tox-icities associated with cytarabine included thrombocytopenia and gastrointestinal disorders.
Dr. Guilhot concluded that "achieving a major cytogenetic response correlates with improved survival. The addition of cytarabine to interferon improves the rate of cytogenetic response, achieves a highly dramatic response at 12 months, and produces the greatest survival benefit."