Review of therapeutic drug monitoring of anticancer drugs part 1 – Cytotoxics

Paci, Angélo; Veal, Gareth J.; Bardin, Christophe; Levêque, Dominique; Widmer, Nicolas; Beijnen, Jos H.; Astier, A.; Chatelut, Étienne

doi:10.1016/j.ejca.2014.04.014

Cited by 215 publications

(197 citation statements)

References 82 publications

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“…Gastrointestinal toxicity in the form of mucositis, causing diarrhoea, pain and weight loss, is a common adverse effect of chemotherapy, resulting in morbidity and mortality 38 . Moreover, it often leads to dose-limitation, which reduces the efficacy of anti-cancer treatment.…”

Section: [H1] Microbial Enzymatic Degradation and Metabolismmentioning

confidence: 99%

Gut microbiota modulation of chemotherapy efficacy and toxicity

Alexander

Wilson

Teare

et al. 2017

Nat Rev Gastroenterol Hepatol

665

560

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Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation & compromise of anti-cancer effects, and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies and gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: namely Translocation, Immunomodulation, Metabolism, Enzymatic degradation, andReduced diversity and ecological variation The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

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Section: [H1] Microbial Enzymatic Degradation and Metabolismmentioning

confidence: 99%

Gut microbiota modulation of chemotherapy efficacy and toxicity

Alexander

Wilson

Teare

et al. 2017

Nat Rev Gastroenterol Hepatol

665

560

View full text Add to dashboard Cite

show abstract

“…Several studies have investigated individualization in 5-FU-based chemotherapy based on the 5-FU metabolism-associated enzymatic and genetic characteristics of the individual patient (22)(23)(24)(25)(26)(27)(28)(29). In addition, the individualization of 5-FU-based chemotherapy based on the serum 5-FU concentration has been reported lately (30)(31)(32)(33)(34). However, individualization in 5-FU-based chemotherapy remains to be implemented in a clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Impact of the individualization of the first‑line chemotherapy for advanced colorectal cancer based on collagen gel droplet‑embedded drug sensitivity test

Ochiai¹,

Nishimura²,

Watanabe³

et al. 2017

Oncol Lett

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Abstract. Leucovorin (FOL) and fluorouracil (5-FU) plus oxaliplatin (l-OHP; FOLFOX) or FOL and 5-FU plus irinotecan FOLFIRI) are widely used as first-line chemotherapy regimens in the treatment of advanced colorectal cancer (CRC). However, second-line chemotherapy must be abandoned in certain cases due to disease progression, adverse effects or high medical cost. Therefore, the most effective regimen should be selected as first-line chemotherapy. We reported that individualization of first-line treatment (FOLFOX/FOLFIRI/Dual/Poor responder) was possible using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) and that individualized first-line chemotherapy with CD-DST may improve the prognosis of patients with unresectable CRC. The aim of the present prospective cohort study was to evaluate the individualization of first-line chemotherapy using CD-DST, with a focus on prognosis. Between March 2008 and December 2015, tumor specimens were obtained from 120 patients with CRC who had not received preoperative chemotherapy. CD-DST was performed and the growth inhibition rate (IR) was determined by exposure for 24 h with 5-FU and l-OHP (6.0 and 3.0 µg/ml, respectively) and 5-FU and SN-38 (6.0 and 0.2 µg/ml, respectively). The cumulative distribution of IR values under each condition was evaluated on the basis that the clinical response to FOLFOX and FOLFIRI is equivalent (~50%). The prognosis of dual responder was improved compared with that of poor responders, however this difference was identified to be significant. There was no different prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen in dual responders. However, in poor responders, there were significant differences of prognosis between patients treated with an appropriate first-line regimen and patients treated with an inappropriate first-line regimen (P= 0.036). In conclusion, the results from the present study suggest that administration of the recommended first-line regimen using CD-DST for patients with unresectable CRC is important for the improvement of prognosis, particularly in poor responders.

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“…The anticancer drugs of clinical importance show the malignant cell toxicity selectively (Paci et al, 2014). Their toxicity is an additional burden on the patients undergoing chemotherapy (Kasetty et al, 2012).…”

Section: Mechanism Of Toxicity Of Anticancer Drugsmentioning

confidence: 99%

Toxicity of anticancer drugs and its prevention with special reference to role of garlic constituents

Raisuddin¹,

Ahmad²,

Fatima³

et al. 2018

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Cancer is the leading cause of death globally. World Health Organisation (WHO) reported that 70% of death caused by cancer occurs in low or middle income countries which may be due to unavailability of correct treatment or delayed medical support. Despite of different therapies available to cure the cancer or to prolong the life of cancer survivors; chemotherapy is still central to cancer therapy. Administration of chemotherapeutic drugs either independently or in combination with other therapies such as irradiation or surgery provides relief to cancer patients. Nitrogen mustards were the first anticancer agents used in chemotherapy in 1940s. Their clinical use accelerated the development of different anticancers drugs. Due to the reports of toxicities of these anticancer drugs, herbal remedies for cancer treatment found notion of oncologists. A number of herbal extracts and natural products have shown the potential of anticancer activity. They also reduce the toxicity of synthetic anticancer drugs. Garlic (Allium sativum L.) is one of the herbal remedies with high anticancer potentia l and ability to mitigate the toxicities of anticancer drugs. The protective effects of garlic against the toxicities of anticancer drugs have been reported in a number of studies and it has also been reported that fresh garlic and aged garlic extra ct show considerable protective effects. Allicin (diallyl thiosulfinate) is the major pharmacological component of garlic which has attracted attention of the international medical field gradually due to its potential for disease prevention and trea tment. The major unique organosulfur compounds in aged garlic extract such as water-soluble S-allyl cysteine (SAC) and Sallylmercaptocysteine (SAMC) have potent antioxidant activity. Many reports show the protective potential of these garlic constituents against anticancer drug-induced toxicities. Here, we present review of toxicities caused by anticancer drugs and their mechanism of action along with the efficacy of some plant extracts and natural products in reducing toxicity of anticancer drugs with special reference to of garlic constituents.

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Review of therapeutic drug monitoring of anticancer drugs part 1 – Cytotoxics

Cited by 215 publications

References 82 publications

Gut microbiota modulation of chemotherapy efficacy and toxicity

Gut microbiota modulation of chemotherapy efficacy and toxicity

Impact of the individualization of the first‑line chemotherapy for advanced colorectal cancer based on collagen gel droplet‑embedded drug sensitivity test

Toxicity of anticancer drugs and its prevention with special reference to role of garlic constituents

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