Oral versus intravenous fluoropyrimidines for colorectal cancer

Chionh, Fiona; Campbell, Ainsley; Sukumaran, Shawgi; Price, Timothy; Tebbutt, Niall C.

doi:10.1002/14651858.cd008398

Cited by 15 publications

(27 citation statements)

References 47 publications

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“…Although the data reported in this manuscript are from a small study, where the majority of the patients were treated with capecitabine monotherapy, the cohort appeared to reflect the disposition of fluoropyrimidines observed in numerous larger studies. In particular, the prospective incidence of G3 and G4 GI toxicity was similar to that reported in larger trials . In addition, the prevalence of deleterious DPYD variants, calculated from the prospective patients only, was similar to the expected prevalence in European populations, which was the predominant ancestry reported in the cohort.…”

Section: Discussionsupporting

confidence: 79%

“…Of particular clinical concern are GI toxicity (diarrhoea and mucositis), hand–foot syndrome and neutropenia. The prevalence of severe to life threatening GI toxicity (Grade 3 or greater) ranges between 10 and 20% and lethal toxicity also occurs . Fluoropyrimidine treatment is discontinued because of these safety concerns in about 8% of patients …”

Section: Introductionmentioning

confidence: 99%

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A case–control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine‐induced gastrointestinal toxicity

Helsby

Duley

Burns

et al. 2019

Brit J Clinical Pharma

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Aims:A previous study suggested that a thymine (THY) challenge dose could detect aberrant pharmacokinetics in known cases of fluoropyrimidine toxicity compared with healthy volunteers. The preliminary data suggested that urine sampling also could detect this aberrant disposition. The aim of this case-control study was to assess the ability of the urinary THY challenge test to discriminate cases of severe gastrointestinal toxicity in a cohort of patients treated with 5-fluorouracil or capecitabine.Methods: Patients (n = 37) received a 250 mg (per os) dose of THY and a cumulative urine sample was collected for 0-4 h. The urinary amounts of THY and metabolite dihydrothymine (DHT) were determined by liquid chromatography/mass spectrometry. Genomic DNA was analysed for DPYD gene variants. Renal function was estimated from blood creatinine levels. Cases (n = 9) and noncases (n = 23) of severe (grade ≥ 3) gastrointestinal toxicity were defined based on Common Terminology Criteria for Adverse Events. Results:The median THY/DHT ratios were 6.2 (interquartile range 2.9-6.4) in cases, including the 2 patients who were DPYD heterozygous carriers. However, this was not significantly different (P = .07) from the THY/DHT in noncases (median 2.6, interquartile range 2.8-4.2). Although creatinine clearance was lower (P = .001) in cases, renal function could not discriminate cases from noncases. However, logistic regression analysis using both of these explanatory variables could discriminate most cases (receiver operating characteristic area 0.8792, 95% confidence interval 0.72-1.00). Conclusions:The THY challenge test combined with a patient's renal function may be useful as a phenotypic diagnostic test to detect risk of life-threatening fluoropyrimidine gastrointestinal toxicity.The authors confirm that the Principal Investigator for this paper was Michael Findlay and that he had direct clinical responsibility for patients.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

A case–control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine‐induced gastrointestinal toxicity

Helsby

Duley

Burns

et al. 2019

Brit J Clinical Pharma

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“…[38][39][40][41] ᭺ Capecitabine is an oral fluoropyrimidine that can substitute IV 5-fluorouracil (5-FU). [42][43][44] A metaanalysis included participants with curative and palliative intent concluded that there was no difference in ORR and OS between PO versus IV when treating colorectal cancer. 45 Additionally, in MBC, oral capecitabine can be used alone or in combination or as a substitution for 5-fluorouracil with other PO/IV/SQ agents in MBC.…”

Section: Oral Administrationmentioning

confidence: 99%

Practical strategies to manage cancer patients during the COVID-19 pandemic: Saudi Oncology Pharmacy Assembly Experts recommendations

Alshamrani

Alharbi

Alkhudair

et al. 2020

J Oncol Pharm Pract

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Purpose During COVID-19 pandemic, cancer patients are considered one of the most vulnerable to infection since they tend to have advanced age, multiple comorbidities, and are often immunosuppressed by their cancer or therapy. Hence, the Saudi Oncology Pharmacy Assembly has issued recommendations to reduce the frequency of cancer patients’ visits to oncology centers during the pandemic while maintaining the access to cancer therapy and minimize the risk of exposure to coronavirus disease. Materials and methods A qualitative methodological approach was conducted in April 2020 using a virtual panel discussion for collection of recommendations. Results A total of 12 expert oncology pharmacy practitioners shared their knowledge and experiences in managing oncology patients during the COVID-19 pandemic. The participants recognized many fundamental recommendations that were already applied in many cancer centers since the start of the COVID-19 outbreak. On that basis, the panelists developed eight practice-related recommendations for action, with a main focus on cancer treatment modification. Conclusions In conclusion, delivering cancer care during the COVID-19 pandemic carries significant challenges. This paper addressed suggestions to properly manage cancer patients during difficult times. Implementing changes in practice mandates a national collaborative effort from different sectors to guarantee the quality and continuity of care. The SOPA expert panel developed these recommendations, to ultimately contribute in maintaining access to cancer therapy while minimizing the risk of COVID-19 exposure.

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“…94 As for oral versus intravenous fluoropyrimidines, there is no difference in the OR (0.64, 95% CI 0.25–1.62) for grade 3–4 mucositis between capecitabine based regimens, and 5-FU based regimens in adjuvant chemotherapy, while the pooled OR favored capecitabine-based regimens in palliative chemotherapy (OR 0.17, 95% CI 0.12–0.24). 95 Mucositis induced by molecular targeting drugs and immunotherapy drugs have not been reported in clinical trials.…”

Section: Possible Interaction Between Isd and Anticancer Drugsmentioning

confidence: 99%

Antitumor pharmacotherapy of colorectal cancer in kidney transplant recipients

Liao

Cui

et al. 2019

Ther Adv Med Oncol

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Renal transplantation has become the sole most preferred therapy modality for end-stage renal disease patients. The growing tendency for renal transplants, and prolonged survival of renal recipients, have resulted in a certain number of post-transplant colorectal cancer patients. Antitumor pharmacotherapy in these patients is a dilemma. Substantial impediments such as carcinogenesis of immunosuppressive drugs (ISDs), drug interaction between ISDs and anticancer drugs, and toxicity of anticancer drugs exist. However, experience of antitumor pharmacotherapy in these patients is limited, and the potential risks and benefits have not been reviewed systematically. This review evaluates the potential impediments, summarizes current experience, and provides potential antitumor strategies, including adjuvant, palliative, and subsequent regimens. Moreover, special pharmaceutical care, such as ISDs therapeutic drug monitoring, metabolic enzymes genotype, and drug interaction, are also highlighted.

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Oral versus intravenous fluoropyrimidines for colorectal cancer

Cited by 15 publications

References 47 publications

A case–control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine‐induced gastrointestinal toxicity

A case–control study to assess the ability of the thymine challenge test to predict patients with severe to life threatening fluoropyrimidine‐induced gastrointestinal toxicity

Practical strategies to manage cancer patients during the COVID-19 pandemic: Saudi Oncology Pharmacy Assembly Experts recommendations

Antitumor pharmacotherapy of colorectal cancer in kidney transplant recipients

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