Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5‐Fluorouracil Therapy

Beumer, Jan H.; Chu, Edward; Allegra, Carmen J.; Tanigawara, Yusuke; Milano, Gérard; Diasio, Robert B.; Kim, Tae Won; Mathijssen, Ron H.J.; Zhang, Li; Arnold, Dirk; Muneoka, Katsuki; Boku, Narikazu; Joerger, Markus

doi:10.1002/cpt.1124

Cited by 99 publications

(106 citation statements)

References 88 publications

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“…DPD), age, and organ function have been associated with the variability of 5-FU clearance. Current dosing based on BSA reaches the target concentration of 20-30 mgh/l in only $25% of patients, leaving the majority underexposed [63]. The observation of a higher proportion of women reaching therapeutic concentrations of 5-FU is independent of anthropometric factors [50], such as body weight or BSA [63].…”

Section: Sex Differences In the Pharmacology Of Anticancer Drugsmentioning

confidence: 98%

“…Current dosing based on BSA reaches the target concentration of 20-30 mgh/l in only $25% of patients, leaving the majority underexposed [63]. The observation of a higher proportion of women reaching therapeutic concentrations of 5-FU is independent of anthropometric factors [50], such as body weight or BSA [63]. Temozolomide is another example of a drug with a significantly higher clearance in men: in a study of 35 glioma patients, the clearance was 19% higher in men [53].…”

Section: Sex Differences In the Pharmacology Of Anticancer Drugsmentioning

confidence: 99%

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Gender medicine and oncology: report and consensus of an ESMO workshop

et al. 2019

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Background: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018. Design: Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here. Results: Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy. Conclusion: Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.

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Section: Sex Differences In the Pharmacology Of Anticancer Drugsmentioning

confidence: 98%

Section: Sex Differences In the Pharmacology Of Anticancer Drugsmentioning

confidence: 99%

Gender medicine and oncology: report and consensus of an ESMO workshop

et al. 2019

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“…Cisplatin is one of the most widely used anticancer agents [44], and 5-fluorouracil is the first-line chemotherapeutic agent for CRC [45]. Unfortunately, chemoresistance severely limits the therapeutic potential of these drugs in CRC.…”

Section: Discussionmentioning

confidence: 99%

Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer

et al. 2020

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Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

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“…However, when 5-FU AUC is lower than the target, subsequent 5-FU dosage should be increased; otherwise, 5-FU dosage should be reduced. [6][7][8][9][10][11] Since March 2015, our hospital has been using 5-FU plasma concentration monitoring with the aim of exploring its reference value and comparing its clinical efficacy and safety for patients with advanced colorectal cancer in China. Herein, we reviewed all patients who underwent 5-FU plasma concentration monitoring from the initiation of this technology to August 2018.…”

Section: Introductionmentioning

confidence: 99%

A retrospective analysis of plasma concentration monitoring of fluorouracil in patients with advanced colorectal cancer

Yang

et al. 2019

Eur J Hosp Pharm

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Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5‐Fluorouracil Therapy

Cited by 99 publications

References 88 publications

Gender medicine and oncology: report and consensus of an ESMO workshop

Gender medicine and oncology: report and consensus of an ESMO workshop

Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer

A retrospective analysis of plasma concentration monitoring of fluorouracil in patients with advanced colorectal cancer

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