Gemtuzumab ozogamicin

Gemtuzumab ozogamicin ^?

Monoclonal antibody
Type	Whole antibody
Source	Humanized (from mouse)
Target	CD33
Clinical data
Trade names	Mylotarg
AHFS/Drugs.com	monograph
MedlinePlus	a607075
Pregnancy cat.	D
Legal status	℞-only (US)
Routes	Intravenous
Identifiers
CAS number	220578-59-6 Y
ATC code	L01XC05
DrugBank	DB00056
KEGG	D03259 Y
ChEMBL	CHEMBL1201506 N
Chemical data
Formula	?
Mol. mass	151–153 kDa
N(what is this?)  (verify)

Gemtuzumab ozogamicin (marketed by Wyeth as Mylotarg) is a drug-linked monoclonal antibody that was used to treat acute myelogenous leukemia from 2000-2010. It was withdrawn from market in June 2010 when a clinical trial showed the drug increased patient death and added no benefit over conventional cancer therapies.

Gemtuzumab is a monoclonal antibody to CD33 linked to a cytotoxic agent from the class of calicheamicins. CD33 is expressed in most leukemic blast cells but also in normal hematopoietic cells, the intensity diminishing with maturation of stem cells. In the United States, it was approved under an accelerated-approval process by the FDA in 2000 for use in patients over the age of 60 with relapsed acute myelogenous leukemia (AML); or those who are not considered candidates for standard chemotherapy.^[1]

Within the first year after approval, the FDA required a black box warning be added to Gemtuzumab packaging. The drug was noted to increase the risk of veno-occlusive disease in the absence of bone marrow transplantation.^[2] Later the onset of VOD was shown to occur at increased frequency in Gemtuzumab patients even following bone marrow transplantation.^[3] The drug was discussed in a 2008 JAMA article, which criticized the inadequacy of postmarketing surveillance of biologic agents.^[4]

Common side effects of administration included shivering, fever, nausea and vomiting. Serious side effects included severe myelosuppression (suppressed activity of bone marrow, which is involved in formation of various blood cells [found in 98% of patients]), disorder of the respiratory system, tumor lysis syndrome, Type III hypersensitivity, venous occlusion, and death.

Withdrawal from market

A randomized phase 3 comparative controlled trial (SWOG S0106) was initiated in 2004 by Wyeth in accordance with the FDA accelerated-approval process. The study was stopped prior to completion due to worrisome outcomes. Among the patients evaluated, fatal toxicity rate was significantly higher in the gemtuzumab combination therapy group vs the standard therapy group. Mortality was 5.7% with gemtuzumab and 1.4% without the agent (16/283 = 5.7% vs 4/281 = 1.4%; P = .01).^[5]

In June 2010, Pfizer withdrew Mylotarg from the market at the request of the US FDA.^[6][7]

See also

• Inotuzumab ozogamicin

References

1. ^ Bross PF, Beitz J, Chewn G, Chen XH, Duffy E, Kieffer L, Roy S, Sridhara R, Rahman A, Williams G, Pazdur R (2001). "Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia.". Clin Cancer Res 7 (6): 1490–6. PMID 11410481. 
2. ^ Giles FJ, Kantarjian HM, Kornblau SM, Thomas DA, Garcia-Manero G, Waddelow TA, David CL, Phan AT, Colburn DE, Rashid A, Estey EH (2001). "Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation.". Cancer 92 (2): 406–13. doi:10.1002/1097-0142(20010715)92:2<406::AID-CNCR1336>3.0.CO;2-U. PMID 11466696. 
3. ^ Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, Alyea EP, Antin JH, Stone RM, Soiffer RJ, DeAngelo DJ (2003). "Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation.". Blood 102 (5): 1578–82. doi:10.1182/blood-2003-01-0255. PMID 12738663. 
4. ^ [http://jama.ama-assn.org/content/293/17/2131.abstract The Research on Adverse Drug Events and Reports (RADAR) Project, JAMA
5. ^ [1], Medscape
6. ^ Mylotarg (gemtuzumab ozogamicin): Market Withdrawal, US FDA
7. ^ Pfizer pulls leukemia drug from U.S. market, Reuters

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This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by expanding it.v · Categories: Orphan drugs Monoclonal antibodies for tumors Withdrawn drugs Monoclonal antibody stubs Antineoplastic and immunomodulating drug stubs Wikimedia Foundation. 2010. Игры ⚽ Поможем написать курсовую NXT SoundpaX Mounds Park Academy Look at other dictionaries: Gemtuzumab-Ozogamicin — Masse/Länge Primärstruktur 151 bis 153 kDa …   Deutsch Wikipedia Gemtuzumab ozogamicin — Größe 151 bis 153 kDa Bezeichner Externe IDs …   Deutsch Wikipedia gemtuzumab ozogamicin — A monoclonal antibody combined with a toxic substance that is used treat certain types of acute myeloid leukemia in older patients and is being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory… …   English dictionary of cancer terms gemtuzumab ozogamicin — noun A monoclonal antibody used to treat acute myelogenous leukemia …   Wiktionary gemtuzumab ozogamicin — gem·tu·zu·mab ozo·ga·mi·cin (gem tooґzoo mab″ o″zo gə miґsin) a recombinant DNA–derived monoclonal antibody conjugated with a cytotoxic antitumor antibiotic, calicheamicin, isolated from the bacterium Micromonospora echinospora …   Medical dictionary Gemtuzumab — ozogamicin Größe 151 bis 153 kDa Bezeichner Externe IDs …   Deutsch Wikipedia Ozogamicin — The term ozogamicin in the names of monoclonal antibodies or antibody drug conjugates indicates that they are linked to a cytotoxic agent from the class of calicheamicins, as in: Gemtuzumab ozogamicin Inotuzumab ozogamicin This disambiguation… …   Wikipedia gemtuzumab — A monoclonal antibody combined with a toxic substance that is used treat certain types of acute myeloid leukemia in older patients and is being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory… …   English dictionary of cancer terms Inotuzumab ozogamicin — drugbox type = mab source = Humanized target = CD22 CAS number = 635715 01 4 ATC prefix = ATC suffix = PubChem = DrugBank = C=6518 | H=10002 | N=1738 | O=2036 | S=42 molecular weight = bioavailability = protein bound = metabolism = elimination… …   Wikipedia Cancer immunotherapy — is the use of the immune system to reject cancer. The main premise is stimulating the patient s immune system to attack the malignant tumor cells that are responsible for the disease. This can be either through immunization of the patient, in… …   Wikipedia 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. Mark and share Search through all dictionaries Translate… Search Internet Share the article and excerpts Direct link … Do a right-click on the link above and select “Copy Link”