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Results: 4

1.

Immune suppression

MedGen UID:
326692
Concept ID:
C1840264
Disease or Syndrome
2.

Neoplasm

A general term for autonomous tissue growth in which the malignancy status has not been established and for which the transformed cell type has not been specifically identified. [from NCI]

MedGen UID:
10294
Concept ID:
C0027651
Neoplastic Process
3.

Neoplasm of the large intestine

Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI. [from MeSH]

MedGen UID:
3171
Concept ID:
C0009404
Neoplastic Process
4.

Irinotecan response

Irinotecan is a topoisomerase inhibitor that is widely used in the treatment of cancer. It is often used in combination with other drugs to treat metastatic colorectal cancer. However, irinotecan therapy is associated with a high incidence of toxicity, including severe neutropenia and diarrhea. Irinotecan is metabolized and inactivated by an UDP-glucuronosyltransferase enzyme encoded by the gene UGT1A1. UDP-glucuronosyltransferase enzymes are part of the glucuronidation pathway that transforms small lipophilic molecules, such as certain drugs like irinotecan, into water-soluble, excretable metabolites. Variants of this gene, such as UGT1A1*28, are associated with reduced enzyme activity and an increased risk of irinotecan toxicity. Approximately 10% of North Americans are homozygous for the UGT1A1*28 allele and are more likely to develop neutropenia following irinotecan therapy. The FDA-approved drug label for irinotecan states that "when administered as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele. However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment". A guideline from the Dutch Pharmacogenetics Working Group (KNMP) mentions "although results are not consistent, there is sufficient evidence that a reduction in the initial dose by 30% is required for regimens containing >250 mg/m2 of irinotecan prescribed to homozygous carriers of the UGT1A1*28 allele. This is in agreement with the Food and Drug Administration–mandated label change. No dose reduction is recommended for heterozygous carriers of the UGT1A1*28 allele because dose reduction might result in under treatment". A guideline from the Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group (published in 2009, prior to the FDA statement or KNMP guideline) states that "the evidence is currently insufficient to recommend for or against the routine use of UGT1A1 genotyping in patients with metastatic colorectal cancer who are to be treated with irinotecan, with the intent of modifying the dose as a way to avoid adverse drug reactions (severe neutropenia)". [from Medical Genetics Summaries]

MedGen UID:
450461
Concept ID:
CN077989
Sign or Symptom

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