TY - JOUR
T1 - Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase
AU - O'Brien, Susan
AU - Giles, Francis
AU - Talpaz, Moshe
AU - Cortes, Jorge
AU - Rios, Mary Beth
AU - Shan, Jianqin
AU - Thomas, Deborah
AU - Andreeff, Michael
AU - Kornblau, Steven
AU - Faderl, Stefan
AU - Garcia-Manero, Guillermo
AU - White, Kevin
AU - Mallard, Susie
AU - Freireich, Emil
AU - Kantarjian, Hagop M.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - BACKGROUND. Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-α), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-α, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS. Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m2 IFN-α subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m2 by continuous infusion over 24 hours daily × 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS. With the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to ≥ 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-α dose was 1.6 MU/m2 daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase. CONCLUSIONS. The sequence of IFN-α, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML.
AB - BACKGROUND. Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-α), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-α, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS. Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m2 IFN-α subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m2 by continuous infusion over 24 hours daily × 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS. With the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to ≥ 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-α dose was 1.6 MU/m2 daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase. CONCLUSIONS. The sequence of IFN-α, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML.
KW - Chronic myeloid leukemia
KW - Cytarabine
KW - Homoharringtonine
KW - Interferon-alpha
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U2 - 10.1002/cncr.11620
DO - 10.1002/cncr.11620
M3 - Review article
C2 - 12942553
AN - SCOPUS:0041887168
SN - 0008-543X
VL - 98
SP - 888
EP - 893
JO - Cancer
JF - Cancer
IS - 5
ER -