Simultaneous homoharringtonine and interferon‐α in the treatment of patients with chronic‐phase chronic myelogenous leukemia
Authors: O'Brien Susan , Talpaz Moshe , Cortes Jorge , Shan Jianqin , Giles Francis J. , Faderl Stefan , Thomas Deborah , Garcia‐Manero Guillermo , Mallard Susie , Beth Rios Mary , Koller Charles , Kornblau Steve , Andreeff Michael , Murgo Anthony , Keating Michael , Kantarjian Hagop M. 
Published: August 2002

BACKGROUND

Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon‐α (IFN‐α), and cytarabine (ara‐C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN‐α therapy in patients with chronic‐phase CML who were not exposed previously to either agent.

METHODS

Forty‐seven patients were treated: 37 patients with early chronic‐phase CML (2 patients with clonal evolution) and 10 patients with late chronic‐phase CML. Their median age was 62 years (range, 23–73 years). HHT was given at a dose of 2.5 mg/m2by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN‐α was given daily at a target dose of 5 × 106units/m2subcutaneously. Response, survival, and treatment toxicity were analyzed.

RESULTS

Overall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronic‐phase CML. Among the 10 patients with late chronic‐phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6–24 courses, the median daily IFN‐α dose was 1 MU/m2, and the median number of days on HHT per month was 2 days. With a median follow‐up of 26 months, the estimated 2‐year survival rate was 90% (95% confidence interval, 79–100%).

CONCLUSIONS

The simultaneous combination of HHT and IFN‐α is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal‐transduction inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN‐α chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored. Cancer 2002;94:2024–32. © 2002 American Cancer Society.

DOI 10.1002/cncr.10436