Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264.

Venook, Alan P.; Egorin, Merrill J.; Rosner, Gary L.; Brown, Thomas; Jahan, Thierry; Batist, Gerald; Hohl, Raymond J.; Budman, Daniel R.; Ratain, Mark J.; Kearns, Cristin; Schilsky, Richard L.

doi:10.1200/jco.1998.16.5.1811

Cited by 119 publications

(39 citation statements)

References 9 publications

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“…4,5 Such events often affect the disease response, and are associated with treatmentcourse delays, discontinuations and dose reductions. 6,7 Patients undergoing cytotoxic chemotherapy require careful assessment of their liver function before, during and after chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Role of bicyclol in preventing chemotherapeutic agent-induced liver injury in patients over 60 years of age with cancer

Zhou

Chen

et al. 2014

J Int Med Res

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Objective: To evaluate the efficacy of bicyclol in preventing chemotherapy-induced liver damage. Methods: Patients !60 years of age with cancer were equally randomized into control (chemotherapy alone) or prophylactic (chemotherapy supplemented with 75 mg bicyclol, oral, daily) groups. Liver function indices were assessed immediately before treatment, during each therapy cycle and following treatment. Results: Of 306 patients enrolled, 300 patiets completed the study (n ¼ 147 and n ¼ 153; prophylactic and control groups, respectively). Incidence of grade I-IV elevation of serum transaminase and/or bilirubin was significantly lower in the prophylactic group (17.1%) compared with the control group (47.1%). Incidence of grade II-IV hepatic injury was also significantly lower in the prophylactic group (0.7%) than in the control group (12.4%). Conclusions: Prophylactic bicyclol (75 mg daily) could significantly reduce the incidence and degree of chemotherapeutic agent-induced liver damage in elderly patients with cancer. Further studies are recommended with larger sample sizes and long-term follow up.

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Section: Introductionmentioning

confidence: 99%

Role of bicyclol in preventing chemotherapeutic agent-induced liver injury in patients over 60 years of age with cancer

Zhou

Chen

et al. 2014

J Int Med Res

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“…Supporting this possibility are the data of Yamamoto et al (5), who found independent correlation of docetaxel clearance with cytochrome P4503A4 activity, serum levels of ␣-1 acid glycoprotein, and baseline transaminase activity in patients with normal total bilirubin and hepatic transaminase levels. Like docetaxel, elevated bilirubin or transaminase levels correlate with reduced clearance of paclitaxel and paclitaxel metabolites, increased AUC, and greater toxic effects (11). However, unlike docetaxel, alkaline phosphatase, total bilirubin, and transaminase values within the normal range failed to predict toxicity of paclitaxel in our population.…”

Section: Discussionmentioning

confidence: 61%

Patient Characteristics Compete with Dose as Predictors of Acute Treatment Toxicity in Early Phase Clinical Trials

Rogatko¹,

Babb²,

Wang³

et al. 2004

Clinical Cancer Research

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Purpose: The purpose of this study was to identify patient characteristics that may be risk factors or markers of susceptibility to adverse treatment effects in cancer Phase I and II clinical trials.Patients and Methods: A total of 459 patients enrolled in 23 therapeutic Phase I and II studies at the Fox Chase Cancer Center were included in the analysis. Patient-specific characteristics, medical and treatment history, doses of experimental agents, and graded toxicities were extracted from case report forms. We developed a novel summary measure, the toxicity index (TI), to better discriminate patients on the basis of their overall toxicity experiences. Mixed model ANOVA was used to model TI on the basis of data from all trials using a specific agent. Generalized estimating equations in the context of binary logistic regression were used to model dose-limiting toxicity.Results: Seventeen pretreatment factors, including performance status, alkaline phosphatase, total bilirubin, serum creatinine, and tobacco use, emerged as significant predictors of toxicity as defined by dose-limiting toxicity or TI. Unexpectedly, dose was not always a predictor of toxicity. Even for values within the normal range, the TI identified serum bilirubin and alkaline phosphatase as predictors of toxicity after treatment with docetaxel and alkaline phosphatase as a predictor for toxicity after treatment with irinotecan.Conclusions: Independent of dose, certain pretreatment characteristics, including measures of organ function that are in the normal range, were found to be predictors of treatment toxicity. Because of its sensitivity to differences in overall toxicity, the TI should prove to be a useful tool for identifying predictors of chemotherapy-related toxicity.

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“…Venook et al [31] prospectively studied the PKs of both the 24-hour and 3-hour infusions of paclitaxel in patients with hepatic dysfunction, and found that dose reductions were necessary in patients with elevated AST or bilirubin (cohorts: (a) AST 2ϫ ULN and bilirubin Ͻ1.5 mg/dl, (b) bilirubin 1.6 -3 mg/dl with any level of AST, and (c) bilirubin Ͼ3 mg/dl with any level of AST) to prevent myelosuppression and neutropenic sepsis-related deaths. Investigators found that, for a 24-hour infusion of paclitaxel, doses Ͼ50 -75 mg/m 2 were not tolerated by patients with liver dysfunction.…”

Section: Paclitaxelmentioning

confidence: 99%

“…Investigators found that, for a 24-hour infusion of paclitaxel, doses Ͼ50 -75 mg/m 2 were not tolerated by patients with liver dysfunction. For the 3-hour infusion, doses of 100 mg/m 2 could be given to patients with moderate liver dysfunction, but for patients with severe liver impairment (bilirubin Ͼ3 mg/dl), doses had to be reduced to 50 mg/m 2 [31].…”

Section: Paclitaxelmentioning

confidence: 99%

Commentary: Oncologic Drugs in Patients with Organ Dysfunction: A Summary

2007

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After completing this course, the reader will be able to:1. Describe the currently recommended dose adjustments for common chemotherapeutics in oncology patients with organ dysfunction.2. Explain the rationale for using phase I dose-escalation studies to determine appropriate chemotherapy dosing in patients with organ dysfunction.3. Discuss the limitations of the currently available studies to guide chemotherapy dose adjustment in patients with organ dysfunction.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThere are few prospective data regarding the pharmacokinetics and clinical toxicity of commonly used chemotherapeutics in cancer patients with organ dysfunction. Although increasing numbers of studies are investigating newer chemotherapeutics in patients with liver or kidney dysfunction, most guidelines for dosing, especially for established agents, remain empiric. This review describes the available data (both prospective and case study) evaluating the impact of renal and hepatic dysfunction on toxicity and dosing of commonly used chemotherapeutics and provides a practical summary for their use in this setting.

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Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264.

Abstract: If paclitaxel is used for patients with elevated levels of AST or bilirubin, dose reductions are necessary, and an increase in toxicity can be anticipated. The increased myelosuppression observed is at least partially because of altered paclitaxel pharmacokinetics in such patients.

Cited by 119 publications

References 9 publications

Role of bicyclol in preventing chemotherapeutic agent-induced liver injury in patients over 60 years of age with cancer

Role of bicyclol in preventing chemotherapeutic agent-induced liver injury in patients over 60 years of age with cancer

Patient Characteristics Compete with Dose as Predictors of Acute Treatment Toxicity in Early Phase Clinical Trials

Commentary: Oncologic Drugs in Patients with Organ Dysfunction: A Summary

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