Breast Cancer Res Treat. 2007 Jan;101(1):113-21. Epub 2006 Nov 18.
The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen.
Goetz MP,
Knox SK,
Suman VJ,
Rae JM,
Safgren SL,
Ames MM,
Visscher DW,
Reynolds C,
Couch FJ,
Lingle WL,
Weinshilboum RM,
Fritcher EG,
Nibbe AM,
Desta Z,
Nguyen A,
Flockhart DA,
Perez EA,
Ingle JN.
Department of Oncology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN , 55905, USA,
goetz.matthew@mayo.edu.
BACKGROUND: Tamoxifen is biotransformed to the potent anti-estrogen, endoxifen, by the cytochrome P450 (CYP) 2D6 enzyme. CYP2D6 genetic variation and inhibitors of the enzyme markedly reduce endoxifen plasma concentrations in tamoxifen-treated patients. Using a North Central Cancer Treatment Group adjuvant tamoxifen trial, we performed a comprehensive evaluation of CYP2D6 metabolism by assessing the combined effect of genetic variation and inhibition of the enzyme system on breast cancer recurrence and death. METHODS:
Medical records were reviewed at each randomizing site to determine whether CYP2D6 inhibitors were co-prescribed with tamoxifen. Extensive metabolizers were defined as patients without a *4 allele (i.e., wt/wt) who were not co-prescribed a CYP2D6 inhibitor. Patients with decreased CYP2D6 metabolism were classified as intermediate or poor metabolizers (PM) based on the presence of one or two CYP2D6*4 alleles or the co-administration of a moderate or potent CYP2D6 inhibitor. The association between CYP2D6 metabolism and clinical outcome was assessed using Cox modeling. RESULTS: Medication history was available in 225/256 eligible patients and CYP2D6*4 genotype in 190 patients. Thirteen patients (6%) were co-prescribed a CYP2D6 inhibitor [potent (n = 3), moderate (n = 10)], resulting in the following CYP2D6 metabolism: extensive (n = 115) and decreased (n = 65). In the multivariate analysis, patients with decreased metabolism had significantly shorter time to recurrence (p = 0.034; adj HR = 1.91; 95% CI 1.05-3.45) and worse relapse-free survival (RFS) (p = 0.017; adj HR = 1.74; 1.10-2.74); relative to patients with extensive metabolism. Cox' modeling demonstrated that compared to extensive metabolizers, PM had the most significant risk of breast cancer relapse (HR 3.12, p = 0.007). CONCLUSION:
CYP2D6 metabolism, as measured by genetic variation and enzyme inhibition, is an independent predictor of breast cancer outcome in post-menopausal women receiving tamoxifen for early breast cancer. Determination of CYP2D6 genotype may be of value in selecting adjuvant hormonal therapy and it appears CYP2D6 inhibitors should be avoided in tamoxifen-treated women.
PMID: 17115111 [PubMed - indexed for MEDLINE]
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Was it the addition of Fluoxetine or the innate metabolism of the patient? Tamoxitest can test for the latter.
Is Mirtazapine And Fluoxetine Helpful In Treating Pancreatic Cancer?
24 Sep 2008
The treatment of pancreatic cancer remains a great challenge. The majority of patients with pancreatic cancer developed major depression. Antidepressant treatment has been accepted as one of the new strategies in cancer adjuvant therapy. However, systemic studies on the treatment of depression in patients with cancer have not been well documented.
A research article published in the
World Journal of Gastroenterology addresses this question. The research team led by Dr. Jia Lin evaluated the effectiveness of mirtazapine and fluoxetine on body weight, ingestive behavior, locomotor activity and tumor growth
in a pancreatic cancer mouse model in the six-week period trial.
In this study, the researchers observed that
mirtazapine had the effectiveness of increasing appetite, partly reversed the rate of weight loss. In addition, the potential effectiveness of weight gain associated with an increase in food intake. However,
fluoxetine produced a significant suppression of food intake and promoted weight loss. These effects lasted a long-term. Mirtazapine and fluoxetine didn't affect the pancreatic tumor growth. Mirtazapine had more quickly efficacy on the adaptability to new environment than fluoxetine.
Reference: Jia L, Shang YY, Li YY. Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice.
World J Gastroenterol 2008; 14(27): 4377-4382
http://www.wjgnet.com/1007-9327/14/4377.asp
"Excessive Weight Loss
- Fluoxetine without dietary restrictions usually results in only a few pounds lost. Sometimes selective serotonin reuptake inhibitors can cause significant weight loss. Patients who have anorexia or malnutrition should be monitored while taking fluoxetine to prevent life threatening complications."
Hybrid Mode
