Phase I and pharmacokinetic trial of weekly CPT-11.

Rothenberg, Mace L.; Kuhn, John G.; Burris, Howard A.; Nelson, Joelle; Eckardt, John R.; Tristan-Morales, M; Hilsenbeck, Susan G.; Weiss, Geoffrey R.; Smith, Lon; Rodriguez, G. I.

doi:10.1200/jco.1993.11.11.2194

Cited by 263 publications

(105 citation statements)

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“…10 The mean terminal half-life of SN-38 in plasma is longer than that of CPT-11: 11.5 Ϯ 3.8 hours versus 6.3 Ϯ 2.2 hours for the lactone forms. 11 The bioactivation of CPT-11 to SN-38 is believed to take place in the liver. SN-38 is further conjugated to a glucuronide (SN-38G).…”

mentioning

confidence: 99%

Irinotecan Treatment for Recurrent Malignant Glioma Using an Every-3-Week Regimen

Cloughesy

Filka

Nelson

et al. 2002

American Journal of Clinical Oncology

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mentioning

confidence: 99%

Irinotecan Treatment for Recurrent Malignant Glioma Using an Every-3-Week Regimen

Cloughesy

Filka

Nelson

et al. 2002

American Journal of Clinical Oncology

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“…But its usage always be limited by its severe side effects especially diarrhea and myelosuppression which are doselimiting toxicities (Negoro et al, 1991;Rothenberg et al, 1993;Rougier et al, 1998;Saltz et al, 2000;Rothenberg et al, 2001;Vanhoefer et al, 2001;Fuchs et al, 2003). Clinical administration dosage is generally calculated according to the body surface area or weight presently which is the group average dose (Reilly and Workman, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Because CPT-11 causes severe diarrhea and neutropenia in 20% to 35% of patients treated (Negoro et al, 1991;Rothenberg, et al, 1993;Rougier et al, 1998;Saltz et al, 2000;Rothenberg et al, 2001;Vanhoefer et al, 2001;Fuchs et al, 2003), and fatal events (up to 5.3% prevalence) during single-agent irinotecan treatment have been reported (Vanhoefer et al, 2001). We associated these two kind side effects with UGT1A1 genotypes, clinic characters and each other to detect the relationship between them by multivariate logistic analysis We took the sex, age, KPS, number of metastasis, history of chemotherapy, UGT1A1 genotype, dosage, leucopenia, neutropenia, primary cancer and pathological type into risk factors.…”

Section: Figure 2 Serum Total Bilirubin Distribution Of Different Gementioning

confidence: 99%

“…Although it prolongs survival, patients who treated with chemotherapy include irinotecan is often accompanied by unpredictable and sever side effects. It causes severe diarrhea and neutropenia in 20% to 35% of patients treated (Negoro et al, 1991;Rothenberg et al, 1993;Rougier et al, 1998;Saltz et al, 2000;Othenberg et al, 2001;Vanhoefer et al, 2001;Fuchs et al, 2003). Fatal events (up to 5.3% prevalence) during single-agent irinotecan treatment have been reported (Vanhoefer et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

Lu¹,

Huang²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia (p p<0.05. Conclusions: Our study support the conclusion that patients with a UGT1A1*28 allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the UGT1A1*28 allele (s) did not increase severe neutropenia. Higher serum of CPT-11.

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“…Irinotecan (Camptosar ® ; Pfizer Pharmaceuticals; New York, NY, http://www.pfizer.com) is a semisynthetic analogue of camptothecin and requires metabolic activation by carboxylesterase to form the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), which in turn inhibits topoisomerase-I [17]. SN-38 is further detoxified via formation of SN-38 glucuronide (SN38G).…”

Section: Udp-glucuronosyltransferase 1a1 and Irinotecanmentioning

confidence: 99%

Cancer Pharmacogenomics: Powerful Tools in Cancer Chemotherapy and Drug Development

et al. 2005

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Interindividual differences in tumor response and normal tissue toxicities are consistently observed with most chemotherapeutic agents or regimens. While many clinical variables have been associated with drug responses (e.g., age, gender, diet, drug-drug interactions), inherited variations in drug disposition (metabolism and transport) genes and drug target genes also likely contribute to the observed variability in cancer treatment outcome. Pharmacogenomic studies aim to elucidate the genetic bases for interindividual differences and to use such genetic information to predict the safety, toxicity, and/or efficacy of drugs. There exist several clinically relevant examples of the utility of pharmacogenomics that associate specific genetic polymorphisms in drug metabolizing enzymes (e.g., TPMT, UGT1A1, DPD), drug transporters (MDR1) , INTRODUCTIONPharmacogenomics is a rapidly growing field that aims to elucidate the genetic basis for interindividual differences in drug response and to use such genetic information to predict the safety, toxicity, and/or efficacy of drugs in individual patients or groups of patients. While drug-drug The Oncologist ® Clinical Pharmacology LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Explain how genetic factors contribute to variability in drug response.2. Apply this understanding to clinical outcomes in patients treated with specific chemotherapy agents. Describe approaches for improving clinical cancer therapy and cancer drug development.Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CME by guest on August 28, 2018 http://theoncologist.alphamedpress.org/ Downloaded fromThis material is protected by U.S. Copyright law.Unauthorized reproduction is prohibited. For reprints contact: Reprints@AlphaMedPress.com interactions and environmental factors significantly contribute to interindividual variability in drug response, genetic factors (e.g., inherited variability of drug targets, drug metabolizing enzymes, and/or drug transporters) also appear to have a major impact on drug response and disposition (Fig. 1). Considering the significant heterogeneity associated with patient responses to chemotherapeutic agents and their narrow therapeutic indices, pharmacogenomics has the potential to offer individualized cancer treatment regimens [1][2][3]. Clearly, a better understanding of the genetic determinants of chemotherapeutic response will enable prospective identification of patients at risk for severe toxicity or those most likely to benefit from a particular treatment regimen. Such studies can be translated to clinical practice via molecular diagnostics (genotyping) in order to guide selection of the optimal drug combination and dosage for the individual patient. A number of detailed reviews on cancer pharmacogenomics have been published recently [1][2][3][4][5][6]. This article focuses on the current and future applications of pharmacogenomics in clinical cancer therapy and cance...

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Phase I and pharmacokinetic trial of weekly CPT-11.

Abstract: The MTD for CPT-11 in this patient population was 150 mg/m2/wk when administered on a weekly-times-four schedule repeated every 6 weeks. At dose levels greater than 150 mg/m2/wk, diarrhea is dose-limiting.

Cited by 263 publications

References 11 publications

Irinotecan Treatment for Recurrent Malignant Glioma Using an Every-3-Week Regimen

Irinotecan Treatment for Recurrent Malignant Glioma Using an Every-3-Week Regimen

Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

Cancer Pharmacogenomics: Powerful Tools in Cancer Chemotherapy and Drug Development

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