Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

Abstract5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines.

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Effect of PK-guided tamoxifen dose escalation on endoxifen serum concentrations in CYP2D6 intermediate and poor metabolizers.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.595 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 595-595

Author(s):

Frans Opdam ◽

Vincent O. Dezentje ◽

Jan den Hartigh ◽

Henk-jan Guchelaar ◽

Trees Hessing ◽

...

Keyword(s):

Breast Cancer ◽

Side Effects ◽

Cancer Patients ◽

Dose Escalation ◽

Poor Metabolizers ◽

Tamoxifen Treatment ◽

Extensive Metabolizers ◽

Breast Cancer Patients ◽

One Step ◽

Intermediate Metabolizers

595 Background: Breast cancer patients with absent or reduced CYP2D6 activity may benefit less from tamoxifen treatment because of impaired biotransformation to the active metabolite endoxifen. We investigated whether a temporary one-step dose escalation of tamoxifen in CYP2D6 poor (PM) and intermediate metabolizers (IM) could increase endoxifen serum concentration to a similar level observed in CYP2D6 extensive metabolizers (EM) without increasing toxicity. Methods: From a prospective study population of early breast cancer patients using tamoxifen, 12 CYP2D6 poor and 12 intermediate metabolizers were selected and included in a one-step tamoxifen dose escalation study during two months. The escalation dose (120 mg maximum) was calculated by multiplying the individual’s endoxifen level divided by the median endoxifen concentration (33.7 nM) observed in CYP2D6 extensive metabolizers by 20 mg. Toxicity was assessed and all patients returned to the standard dose of 20 mg after two months. Results: Tamoxifen dose escalation in CYP2D6 poor and intermediate metabolizers significantly increased endoxifen concentrations (PMs: from 8.0 nM to 27.3 nM, p<0.001; IMs: from 17.8 nM to 30.3 nM, p=0.002) without increasing side effects. In intermediate but not in poor metabolizers dose escalation increased endoxifen to levels comparable with those observed in extensive metabolizers using tamoxifen 20 mg once daily (33.7 nM). Conclusions: CYP2D6 genotype and endoxifen guided tamoxifen dose escalation increased endoxifen concentrations without increasing short term side effects. Whether such tamoxifen dose escalation is effective and safe in view of long term toxic effects is uncertain and needs to be explored. Clinical trial information: NTR1509.

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ABCB1 gene polymorphisms and response to chemotherapy in breast cancer patients: A meta-analysis

Surgical Oncology ◽

10.1016/j.suronc.2017.09.004 ◽

2017 ◽

Vol 26 (4) ◽

pp. 473-482 ◽

Cited By ~ 8

Author(s):

Adela Madrid-Paredes ◽

Marisa Cañadas-Garre ◽

Antonio Sánchez-Pozo ◽

Manuela Expósito-Ruiz ◽

Miguel Ángel Calleja-Hernández

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Gene Polymorphisms ◽

Meta Analysis ◽

Breast Cancer Patients ◽

Abcb1 Gene ◽

Response To Chemotherapy

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Early Stage Breast Cancer Patients Treated at an Academic Facility are More Likely to Receive Hypofractionation: A National Cancer Database Analysis

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2017.06.678 ◽

2017 ◽

Vol 99 (2) ◽

pp. E36-E37

Author(s):

M.P. Mitchell ◽

X. Shen ◽

M.J. Tennapel

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Stage ◽

Early Stage Breast Cancer ◽

National Cancer Database ◽

Breast Cancer Patients ◽

Database Analysis ◽

To Receive

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Attention to diet, exercise, and weight in the oncology clinic: Results of a national patient survey.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10549 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10549-10549

Author(s):

Jennifer A. Ligibel ◽

Lori J. Pierce ◽

Catherine M. Bender ◽

Tracy E Crane ◽

Christina Marie Dieli-Conwright ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Online Survey ◽

Early Stage ◽

Cancer Type ◽

Breast Cancer Patients ◽

Related Factors ◽

Increased Risk ◽

Diet And Exercise ◽

To Receive

10549 Background: Obesity and related factors are increasingly associated with increased risk of developing and dying from cancer. The American Society of Clinical Oncology (ASCO) conducted a survey of cancer patients to assess their experience in receiving recommendations and referrals related to weight, diet and exercise as a part of their cancer care. Methods: An online survey was distributed to potential participants between March and June 2020 via ASCO channels and patient advocacy organizations, with an estimated reach of over 25,000 individuals. Eligibility criteria included being 18 years, living in the US, and having been diagnosed with cancer. Logistic regression was used to determine factors associated with recommendation and referral patterns. Results: In total, 2419 individuals responded to the survey. Most respondents were female (75.5%), 61.8% had an early-stage malignancy, 38.2% had advanced disease, and 49.0% were currently receiving treatment. Breast cancer was the most common cancer type (36.0%). Average BMI was 25.8 kg/m2. The majority of respondents consumed £2 servings of fruits and vegetables per day (50.9%) and exercised £2 times per week (50.4%). Exercise was addressed at most or some oncology visits in 57.5% of respondents, diet in 50.7%, and weight in 28.4%. Referrals were less common: 14.9% of respondents were referred to an exercise program, 25.6% to a dietitian and 4.5% to a weight management program. In multiple regression analyses, racial and ethnicity minority respondents were more likely to receive advice about diet (Odds Ratio [OR] 1.92, 95% CI 1.56-2.38) and weight (OR 1.64, 95% CI 1.23-2.17) compared to non-Hispanic whites, individuals diagnosed with cancer in the past 5 yrs (vs > 5 yrs) were more likely to receive advice about exercise (OR 1.48, 95% CI 1.23-1.79), and breast cancer patients were more likely to receive advice about exercise (OR 1.37, 95% CI 1.11-1.68) and weight (OR 1.46, 95% CI 1.03-2.07) than other cancer patients. Overall, 74% of survey respondents had changed their diet or exercise after cancer diagnosis. Respondents reporting that their oncologist spoke to them about increasing exercise or eating healthier foods were more likely to report a change in behavior than those whose oncologists did not (exercise: 79.6% vs 69.0%, P < 0.001; diet 81.1% vs 71.4%, P < 0.001). Respondents whose oncologist had spoken to them about exercise were more likely to exercise > 2 times per week compared to respondents whose oncologists did not address exercise (53.5% vs 44.1%, P < 0.001). Conclusions: In a national survey of oncology patients, slightly more than half of respondents reported attention to diet and exercise during oncology visits. Provider recommendations for diet and exercise were associated with positive changes in these behaviors. Additional attention to diet and exercise as part of oncology visits is needed to help support healthy lifestyle change in cancer patients.

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