The effect of chemotherapy on acute leukemia in the human

Freireich, Emil J.; Gehan, Edmund A.; Sulman, David; Boggs, Dane R.; Frei, Emil

doi:10.1016/0021-9681(61)90118-7

Cited by 124 publications

(47 citation statements)

References 17 publications

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“…This demonstrates that a CR is a major determinant of patient outcome in this particular group of patients, as it is in other categories of patients with AML. [23][24][25] The proportion of patients age Ն 75 years who were offered anthracycline-based induction chemotherapy in the current study was higher than previously reported in comparable age groups. 6,12 It is interesting to note that this rate is comparable to that reported by Baudard et al Ͼ 10 years ago in patients ages 65-74 years.…”

Section: Discussionmentioning

confidence: 75%

The benefit of induction chemotherapy in patients age ≥ 75 years

Vey

Coso

Bardou

et al. 2004

Cancer

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BACKGROUNDPatients age ≥ 75 years with acute myeloid leukemia (AML) generally are offered palliative treatments instead of induction chemotherapy. The authors conducted a retrospective study comparing the outcomes among these elderly patients with the outcomes among younger patients to assess the impact of intensive treatment approaches in this age group.METHODSOne hundred ten consecutive patients age ≥ 75 years with newly diagnosed AML (excluding patients with acute promyelocytic leukemia) were treated in the authors' center over 10 years. Initial treatment was comprised of anthracycline‐based induction chemotherapy (i.e., intravenous idarubicin or daunorubicin for 3 days plus cytarabine [ARAC] for 7 days [3 + 7 regimen] or oral idarubicin) for 62 patients (56%), antimetabolite‐based chemotherapy (including low‐dose ARAC, oral 6‐mercaptopurine plus methotrexate, or hydroxyurea) for 40 patients (36%), and supportive care only for 8 patients (7%). Results were compared with the results from 200 patients ages 65–74 years who were treated during the same period.RESULTSA complete response (CR) to anthracycline‐based induction therapy was achieved by 23 of 62 patients (37%), and the 2‐year overall survival rate was 22% (which was not statistically different from the group of patients ages 65–74 years). In a multivariate analysis of the entire study group (310 patients), treatment (anthracycline‐based vs. other) and age as continuous variable were found to affect survival significantly. In a Landmark analysis, the achievement of a CR translated into improved survival in patients age ≥ 75 years.CONCLUSIONSPatients age ≥ 75 years should not be excluded systematically from intensive chemotherapy regimens. Decisions should be based on stratification systems that include functional status and comorbidity assessments as well as prognostic factors, such as cytogenetics. Cancer 2004. © 2004 American Cancer Society.

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Section: Discussionmentioning

confidence: 75%

The benefit of induction chemotherapy in patients age ≥ 75 years

Vey

Coso

Bardou

et al. 2004

Cancer

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“…This interpretation relies on the assumption that there is a relationship between CR and subsequent survival. Empirical proof of this relationship in newly diagnosed patients was provided by Freireich et al 3 and, more recently, by Estey et al 4 Is there a similar relationship in patients given first salvage therapy? Figure 1 compares survival in patients with initial remissions Ͻ12 months (or with no initial remissions) according to whether they received HDAC-containing therapy or investigational regimens.…”

Section: Role Of Investigational Therapiesmentioning

confidence: 92%

Treatment of relapsed and refractory acute myelogenous leukemia

Estey

2000

Leukemia

155

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Evidence suggests that the salvage therapy utilized for relapsed and refractory acute myelogenous leukemia (AML) should differ based on the duration of a patient's complete remission (CR), the principal predictor of outcome. While standard regimens have produced higher CR rates than investigational regimens, these rates have not translated into improved survival in patients with initial remission durations of Ͻ1 year. Accordingly, there is no need to give standard regimens to these patients who rather should receive investigational therapy once relapse is discovered. In contrast, in patients with initial remission durations of 1-2 years, standard regimens do increase survival compared to investigational regimens. A somewhat artificial distinction has been placed between phase I and phase II studies. The agents to be studied in phase II trials are many, but the patients are limited, so we need to be more innovative in our trial designs. One such proposal, utilizing a Bayesian selection design which calls for randomizing a small number of patients among several investigational treatments, will be discussed. Leukemia (2000) 14, 476-479.

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“…Using treatment experience from AML, the general view has been that complete or partial remission (CR or PR) is a prerequisite for prolonged OS. 6 The phase III randomized AZA-001 trial demonstrated that azacitidine (Vidaza®, Celgene Corporation, Summit, NJ, USA) significantly prolongs OS in higher-risk MDS compared with conventional care (CCR) (hazard ratio [HR] 0.58 [95%CI: 0.43-0.77], P<0.001). 7 In the AZA-001 study, significantly more patients achieved hematologic improvement (HI) 5 with azacitidine than with CCR (49% vs. 29%, respectively, P<0.0001).…”

Section: Introductionmentioning

confidence: 99%

A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial

et al. 2013

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The phase III AZA-001 study established that azacitidine significantly improves overall survival compared with conventional care regimens (hazard ratio 0.58 [95% confidence interval 0.43-0.77], P<0.001). This analysis was conducted to investigate the relationship between treatment response and overall survival. AZA-001 data were analyzed in a multivariate Cox regression analysis with response as a time-varying covariate. Response categories were "Overall Response" (defined as complete remission, partial remission, or any hematologic improvement) and "Stable Disease" (no complete or partial remission, hematologic improvement, or progression) or "Other" (e.g. disease progression). Achieving an Overall Response with azacitidine reduced risk of death by 95% compared with achieving an Overall These results demonstrate azacitidine benefit on overall survival compared with conventional care regimens in patients with higher-risk myelodysplastic syndromes who achieve hematologic response but never attain complete or partial remission, in addition to the survival advantage conferred by achievement of complete or partial remission. This study was registered with clinicaltrials.gov (NCT00071799).A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial

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The effect of chemotherapy on acute leukemia in the human

Cited by 124 publications

References 17 publications

The benefit of induction chemotherapy in patients age ≥ 75 years

The benefit of induction chemotherapy in patients age ≥ 75 years

Treatment of relapsed and refractory acute myelogenous leukemia

A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial

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