Chronic Myelogenous Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment Option Overview
Treatment of patients with chronic myelogenous leukemia (CML) is usually initiated when the diagnosis is established, which is done by the presence of an elevated white blood cell (WBC) count, splenomegaly, thrombocytosis, and identification of the BCR/ABL (breakpoint cluster region/Abelson) translocation. The optimal frontline treatment for patients with chronic-phase CML is the subject of active clinical evaluation but involves specific inhibitors of the BCR/ABL tyrosine kinase.
In a randomized trial comparing imatinib mesylate with interferon plus cytarabine, with 5 years' median follow-up, imatinib mesylate induced complete cytogenetic responses in more than 80% of newly diagnosed patients; in addition, the annual rate of progression to accelerated phase or blast crisis dropped from 2% to less than 1% in the fourth year on the imatinib arm.[Level of evidence: 1iiDiii] However, most of these continually responding patients still showed detectable evidence of the BCR/ABL translocation by the most sensitive measurement of reverse transcriptase–polymerase chain reaction (RT–PCR).[3,4,5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Although evidence-based survival advantages are unavailable because of crossover in randomized trials, the overall survival rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML.
The anticancer efficacy of the Gonzalez regimen has been investigated in two human studies ( CPMC-IRB-8544 ), both involving patients with pancreatic cancer.
The first study, a prospective nonconsecutive case series conducted by the developer and an associate, included 11 patients diagnosed with adenocarcinoma of the pancreas (stage II through stage IV). None of the patients had received chemotherapy or radiation therapy, and none had undergone surgical resection with curative intent. All the...
Tyrosine kinase inhibitors with greater potency and selectivity for BCR/ABL than imatinib have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients comparing nilotinib with imatinib, the rate of major molecular response at 12 months was 43% and 44% for 2-dose schedules of nilotinib and 22% for imatinib (P < .001 for both comparisons). The rate of complete cytogenetic response at 12 months was 80% and 78% for 2-dose schedules of nilotinib and 65% for imatinib (P < .001 for both comparisons).[Level of evidence: 1iiDiv] Progression to accelerated phase or blast crisis occurred in 11 patients on imatinib (4%) but only occurred in 2 patients (<1%, P = . 01) and 1 patient (<1%, P = .004) for the patients on 2-dose schedules of nilotinib.
Similarly, in a randomized, prospective study of 519 patients comparing dasatinib with imatinib, the rate of major molecular response at 12 months was 46% for dasatinib and 28% for imatinib (P < .0001). The rate of complete cytogenetic response at 12 months was 77% for dasatinib and 66% for imatinib (P = .007).[Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in nine patients (3.5%) on imatinib and in five patients (1.9%) on dasatinib (not statistically different).
Although one of these two studies showed statistically significant decreased rates of progression to accelerated or blastic phase, which may ultimately translate into improved survival, the follow-up period with nilotinib and dasatinib has not been long enough to detect and confirm this prolonged survival with these agents. The preferred initial treatment for newly diagnosed patients with chronic-phase CML could be any of these specific inhibitors of the BCR/ABL tyrosine kinase.