Clarithromycin co-administration does not increase irinotecan (CPT-11) toxicity in colorectal cancer patients

Makihara, Katsuya; Nakamura, Sayaka; Miyagi, Kazuyo; Ueno, Hideki; Nakata, Izumi

doi:10.1007/s00280-017-3388-4

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…Recently, Makihara et al . conducted a study to evaluate the influence of concomitant use of clarithromycin, a potent CYP3A4 inhibitor, on irinotecan toxicity. The study did not identify an increase in irinotecan‐induced toxicity by coadministration of clarithromycin .…”

Section: Discussionmentioning

confidence: 99%

“…They found a significant reduction in the incidence of grades III-IV neutropenia in the experimental group but no differences in grades III-IV diarrhoea [17]. Recently, Makihara et al [18] conducted a study to evaluate the influence of concomitant use of clarithromycin, a potent CYP3A4 inhibitor, on irinotecan toxicity. The study did not identify an increase in irinotecan-induced toxicity by coadministration of clarithromycin [18].…”

Section: Discussionmentioning

confidence: 99%

“… conducted a study to evaluate the influence of concomitant use of clarithromycin, a potent CYP3A4 inhibitor, on irinotecan toxicity. The study did not identify an increase in irinotecan‐induced toxicity by coadministration of clarithromycin . To the best of our knowledge, to date, only one genotypic study, performed in 177 Japanese cancer patients, has evaluated the influence of variants in the CYP3A4 gene on irinotecan‐induced toxicity; no significant association was found .…”

Section: Discussionmentioning

confidence: 99%

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Relevance of CYP3A420, UGT1A137 and UGT1A128* variants in irinotecan‐induced severe toxicity

Riera

Salazar

Virgili

et al. 2018

Brit J Clinical Pharma

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Severe irinotecan-induced toxicity is associated with UGT1A1 polymorphisms. However, some patients develop side-effects despite harbouring a normal UGT1A1 genotype. As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Three-hundred and eight metastatic colorectal cancer patients treated with an irinotecan-containing chemotherapy were studied. The presence of CYP3A4*20, UGT1A1*37 and UGT1A1*28 alleles was tested. Associations between these genetic variants and toxicity were evaluated. UGT1A1*28 was significantly associated with severe diarrhoea, neutropenia and asthenia (P = 0.002, P = 0.037 and P = 0.041, respectively). One patient with the UGT1A1*28/*37 genotype presented with grade IV neutropenia and lethal septic shock. One heterozygous UGT1A1 (*1/*28) patient also carried the CYP3A4*20 allele but did not develop toxicity. We confirm that UGT1A1*37 and UGT1A1*28 are associated with severe toxicity and suggest that the CYP3A4*20 allele does not play a role in irinotecan-induced toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Relevance of CYP3A420, UGT1A137 and UGT1A128* variants in irinotecan‐induced severe toxicity

Riera

Salazar

Virgili

et al. 2018

Brit J Clinical Pharma

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“…Therefore, it is theoretically possible that patients with CYP3A4-metabolized drug treatments would experience increased drug toxicities when co-administration of CYP3A4 inhibitors. However, a (Makihara et al, 2017), possibly due to uridine diphosphate glucuronosyltransferase isoform 1A1, organic anion transporter 1B1, genetic variation factors such as irinotecan-induced wide interindividual variability in drug response and toxicity (Riera et al, 2018). More detailed studies on individualized dose adjustment for cancer patients in clinical practice may be accomplished by developing a combined population pharmacokinetic model of irinotecan and its metabolites to prevent adverse effects caused by excessive drug/metabolite accumulation (Oyaga-Iriarte et al, 2019).…”

Section: Concomitant Drugs Involving Inhibition or Induction Of Cyp3a...mentioning

confidence: 99%

Activation/Inactivation of Anticancer Drugs by CYP3A4: Influencing Factors for Personalized Cancer Therapy

et al. 2023

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Cytochrome P450 3A4 (CYP3A4), one of the most important members of the cytochrome P450 subfamily, is a crucial catalyst in the metabolism of numerous drugs. As it catalyzes numerous processes for drug activation or inactivation, the pharmacological activities and clinical outcomes of anticancer drugs metabolized by CYP3A4 are highly dependent on the enzyme's activity and expression. Due to the complexity of tumor microenvironments and various influencing factors observed in human in vitro models and clinical studies, the pharmacokinetics of most anticancer drugs are influenced by the extent of induction or inhibition of CYP3A4-mediated metabolism, and these details are not fully recognized and highlighted. Therefore, this interindividual variability due to genetic and nongenetic factors, together with the narrow therapeutic index of most anticancer drugs, contributes to their unique set of exposures and responses, which have important implications for achieving the expected efficacy and minimizing adverse events of chemotherapy for cancer in individuals. To elucidate the mechanisms of CYP3A4-mediated activation/inactivation of anticancer drugs associated with personalized therapy, this review focuses on the underlying determinants that contribute to differences in CYP3A4 metabolic activity and provides a comprehensive and valuable overview of the significance of these factors, which differs from current considerations for dosing regimens in cancer therapy. We also discuss knowledge gaps, challenges and opportunities to explore optimal dosing regimens for drug metabolic activation/inactivation in individual patients, with particular emphasis on pooling and analyzing clinical information that affects CYP3A4 activity.

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“…Nevertheless, the usefulness of antibiotics for the duration of CPT11 chemotherapy is controversial. Retrospective analyses conducted at Osaka National Hospital (Osaka, Japan) revealed no difference in the prevalence of grade-3–4 diarrhea between the co-administration group (clarithromycin and CPT11) and the CPT11-monotherapy group in patients with colorectal cancer ( Makihara et al., 2017 ). Another retrospective study found that antibiotics did not improve the therapeutic efficacy of CPT11 in advanced colorectal cancer ( Imai et al., 2020 ).…”

Section: Microbiota As An Intermediary In the Efficacy And Toxicity Of Cpt11 Chemotherapymentioning

confidence: 99%

Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy

Yue

Gao

Wang

et al. 2021

Front. Cell. Infect. Microbiol.

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Irinotecan (CPT11) and its active metabolite ethyl-10-hydroxy-camptothecin (SN38) are broad-spectrum cytotoxic anticancer agents. Both cause cell death in rapidly dividing cells (e.g., cancer cells, epithelial cells, hematopoietic cells) and commensal bacteria. Therefore, CPT11 can induce a series of toxic side-effects, of which the most conspicuous is gastrointestinal toxicity (nausea, vomiting, diarrhea). Studies have shown that the gut microbiota modulates the host response to chemotherapeutic drugs. Targeting the gut microbiota influences the efficacy and toxicity of CPT11 chemotherapy through three key mechanisms: microbial ecocline, catalysis of microbial enzymes, and immunoregulation. This review summarizes and explores how the gut microbiota participates in CPT11 metabolism and mediates host immune dynamics to affect the toxicity and efficacy of CPT11 chemotherapy, thus introducing a new concept that is called “microbiota-host-irinotecan axis”. Also, we emphasize the utilization of bacterial β-glucuronidase-specific inhibitor, dietary interventions, probiotics and strain-engineered interventions as emergent microbiota-targeting strategies for the purpose of improving CPT11 chemotherapy efficiency and alleviating toxicity.

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Clarithromycin co-administration does not increase irinotecan (CPT-11) toxicity in colorectal cancer patients

Abstract: This study did not identify an increase in CPT-11 toxicity by co-administration with CAM.

Cited by 6 publications

References 31 publications

Relevance of CYP3A420, UGT1A137 and UGT1A128* variants in irinotecan‐induced severe toxicity

Relevance of CYP3A420, UGT1A137 and UGT1A128* variants in irinotecan‐induced severe toxicity

Activation/Inactivation of Anticancer Drugs by CYP3A4: Influencing Factors for Personalized Cancer Therapy

Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy

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Clarithromycin co-administration does not increase irinotecan (CPT-11) toxicity in colorectal cancer patients

Abstract: This study did not identify an increase in CPT-11 toxicity by co-administration with CAM.

Cited by 6 publications

References 31 publications

Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan‐induced severe toxicity

Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan‐induced severe toxicity

Activation/Inactivation of Anticancer Drugs by CYP3A4: Influencing Factors for Personalized Cancer Therapy

Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy

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Relevance of CYP3A420, UGT1A137 and UGT1A128* variants in irinotecan‐induced severe toxicity

Relevance of CYP3A420, UGT1A137 and UGT1A128* variants in irinotecan‐induced severe toxicity