New fractionated dosing regimen for anticancer drug significantly improves outcomes for older leukemia patients

April 4, 2012

Using fractionated doses of the targeted anticancer drug gemtuzumab ozogamicin allows for safer delivery of the drug into patients aged 50-70 years with acute myeloid leukaemia (AML) and substantially improves their outcomes. These are the conclusions of an Article published Online First by The Lancet, written by Professor Sylvie Castaigne, Centre Hospitalier de Versailles, France, and colleagues.

Previous studies have shown that treatment of AML with gemtuzumab ozogamicin can cause AML to go into , but the dosing schedule in these other studies was such that complications were frequently reported, including and veno-occlusive disease. In this new study, the authors investigated whether addition of low fractionated-dose gemtuzumab ozogamicin to standard front-line would improve the outcome of patients with this leukaemia without causing excessive toxicity.

This phase 3 randomised trial was undertaken in 26 haematology centres in France. patients aged 50-70 years with previously untreated de novo (primary) acute were randomly assigned in a 1:1 ratio to standard treatment () with or without five doses of intravenous gemtuzumab ozogamicin (3 mg/m² on days 1, 4, and 7 during induction and day 1 of each of the two consolidation chemotherapy courses). The primary endpoint was event-free survival (EFS). Secondary endpoints were relapse-free (RFS), overall survival (OS), and safety.

A total of 280 patients were randomly assigned to the control (n=140) and gemtuzumab ozogamicin groups (n=140), and 139 patients were analysed in each group. Complete response with or without incomplete platelet recovery to induction was 104 (75%) in the control group and 113 (81%) in the gemtuzumab ozogamicin group. At 2 years, EFS was estimated as 17% in the control group versus 41% in the gemtuzumab ozogamicin group . OS was 42% versus 53% , respectively and RFS 23% versus 50% , respectively. Haematological toxicity, particularly persistent thrombocytopenia, was more common in the gemtuzumab ozogamicin group than in the control group (16% vs 3%), without an increase in the risk of death from toxicity.

The authors say: "The results of this study show that the addition of fractionated doses of gemtuzumab ozogamicin to standard chemotherapy improves the survival outcome in patients aged 50-70 years with de novo acute myeloid leukaemia. The regimen [used in this study] allows the delivery of a high cumulative dose of gemtuzumab ozogamicin without excess toxicity. We believe that our results support the reevaluation of the place of gemtuzumab ozogamicin in available front-line therapy for acute myeloid leukaemia."

They add: "The substantial benefit of adding gemtuzumab ozagamicin is noted not only in patients with acute myeloid leukaemia who have favourable cytogenetics, but also in the larger subpopulation of those with intermediate cytogenetics."

In a linked Comment, Dr Elihu Estey, University of Washington Medical Center, Seattle, WA, USA; and Fred Hutchinson Cancer Research Center, Seattle, WA, USA, says: "Should gemtuzumab ozogamicin be approved for treatment of leukaemia? The data suggest a nuanced response. Approval seems warranted for patients with acute promyelocytic leukemia and, in combination with chemotherapy, for with favourable or intermediate risk cytogenetics, irrespective of age; in the best case scenario, cytogenetics might be used predictively. Indeed, experience with gemtuzumab ozogamicin suggests a need to move beyond focusing on an average result. Instead, emphasis needs to be placed on outcome in various subsets of this highly heterogeneous disease."

Explore further: Scientists find new drug target for hard-to-treat leukaemia

More information: Study online: www.thelancet.com/journals/lan … (12)60485-1/abstract

Related Stories

Scientists find new drug target for hard-to-treat leukaemia

March 30, 2012
(Medical Xpress) -- Cancer Research UK scientists have discovered a promising new approach to treat a type of myeloid leukaemia – a cancer with limited treatment options and relatively poor survival, according to research ...

No higher risk of acute leukaemia in close relatives

December 15, 2011
(Medical Xpress) -- Parents, siblings and children of patients with the most common form of acute leukemia do not run a higher risk of developing the disease as was once believed, according to a new study from the Swedish ...

Identifying acute myeloid leukemia gene mutations may indicate risk, best treatment

March 23, 2012
An international group of researchers, including those from Moffitt Cancer Center in Tampa, Fla., have published a paper in the March 14 issue of the New England Journal of Medicine reviewing the results of a study that analyzed ...

Recommended for you

Poliovirus therapy induces immune responses against cancer

September 20, 2017
An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that counter's the ability of cancer cells ...

Scientists restore tumor-fighting structure to mutated breast cancer proteins

September 20, 2017
Scientists at the Virginia Tech Carilion Research Institute have successfully determined the full architecture of the breast cancer susceptibility protein (BRCA1) for the first time. This three-dimensional information provides ...

Brain cancer growth halted by absence of protein, study finds

September 20, 2017
The growth of certain aggressive brain tumors can be halted by cutting off their access to a signaling molecule produced by the brain's nerve cells, according to a new study by researchers at the Stanford University School ...

New clinical trial explores combining immunotherapy and radiation for sarcoma patients

September 20, 2017
University of Maryland School of Medicine researchers are investigating a new approach to treat high-risk soft-tissue sarcomas by combining two immunotherapy drugs with radiation therapy to stimulate the immune system to ...

Researchers identify new target, develop new drug for cancer therapies

September 20, 2017
Opening up a new pathway to fight cancer, researchers at the University of Pennsylvania have found a way to target an enzyme that is crucial to tumor growth while also blocking the mechanism that has made past attempts to ...

Brain powered: Increased physical activity among breast cancer survivors boosts cognition

September 19, 2017
It is estimated that up to 75 percent of breast cancer survivors experience problems with cognitive difficulties following treatments, perhaps lasting years. Currently, few science-based options are available to help. In ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.