ORLANDO--Combination therapy utilizing interferon alfa-2b (Intron A) and 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.
ORLANDO--Combination therapy utilizing interferon alfa-2b (Intron A)and cytarabine is associated with improved cytogenetic response and survivalover interferon alone in patients with chronic myelogenous leukemia (CML),a French study, presented at the 38th Annual Meeting of the American Societyof Hematology (ASH), has shown.
François Guilhot, MD, head of the Department of Hematology andClinical Oncology, Centre Hospitalier Universitaire de Poitiers, presentedthe data for the French CML study group.
The 5-year randomized study included 810 patients with Philadelphiachromosome-positive (Ph+) CML from 70 French centers. All patients weregiven hydroxyurea (Hydrea), 50 mg/kg daily, and interferon at a startingdose of 5 × 106 IU/m²/day. Hydroxyurea was discontinuedonce a complete hematologic remission (CHR) was achieved.
Of 646 evaluable patients, 324 received the interferon alone regimenand 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 responsewas similar in both study arms. At 12 months, a major cytogenetic responsewas obtained in 96 (39%) of 248 patients receiving cytarabine, comparedwith 55 (22%) of 249 patients who did not receive cytarabine (P less than.001).
Survival was significantly improved in the interferon plus cytarabinegroup. The 3-year survival rate was 88% in the combination group, comparedwith 76% in the interferon alone group.
When adjusted for variables of white blood cell count and hemoglobinlevel or Sokal score, overall survival remained significantly improvedin the interferon plus cytarabine group. In both groups, patients who achieveda 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 numberof courses of cytarabine was 7, with a median daily dose of 31 mg. Themedian 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 patientsin both the combination group and in the group receiving interferon alone.Major tox-icities associated with cytarabine included thrombocytopeniaand gastrointestinal disorders.
Dr. Guilhot concluded that "achieving a major cytogenetic responsecorrelates with improved survival. The addition of cytarabine to interferonimproves the rate of cytogenetic response, achieves a highly dramatic responseat 12 months, and produces the greatest survival benefit."