Treatment of advanced malignancies with high-dose acetaminophen and N-acetylcysteine rescue.

Abstract:

:High-dose acetaminophen (HDAC) produces hepatocellular necrosis and cytotoxic changes in other tissues that express mixed-function-oxidase (MFO) activity. N-acetylcysteine (NAC), administered within 8 hr of HDAC exposure, replenishes reduced glutathione and prevents these effects. Numerous cell culture and animal studies have demonstrated that NAC may differentially protect normal cells compared with malignant cells from the toxic effects of chemotherapeutic agents and radiation. It was therefore proposed that HDAC with NAC rescue may be effective in malignancies that express MFO activity. To test this hypothesis, a phase I trial of HDAC with NAC rescue was conducted on 19 patients with advanced cancer. HDAC was escalated from 6 to 20 g/m2 PO using a standard IV NAC rescue regimen. A total of 78 treatments were administered. Moderate fatigue, anorexia, and weight loss were the main toxicities observed. Transient grade 3 liver toxicity was noted following 1 treatment. Alopecia and renal and hematological toxicities were not observed. Responses after 4 courses administered weekly were as follows: response in at least 1 site-8 (partial 3, improved 3, mixed 2); stable disease-3; progressive disease-3; inevaluable-5. In conclusion, HDAC was tolerated with moderate fatigue, anorexia, and weight loss but few other effects using a standard IV NAC rescue regimen. A maximum tolerated dose was not reached at 20 g/m2. A 3/19 (15.8%) partial response rate was observed.

journal_name

Cancer Invest

journal_title

Cancer investigation

authors

Kobrinsky NL,Hartfield D,Horner H,Maksymiuk A,Minuk GY,White DF,Feldstein TJ

doi

10.3109/07357909609012140

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

202-10

issue

3

eissn

0735-7907

issn

1532-4192

journal_volume

14

pub_type

临床试验,杂志文章
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  • Stereotactic Body Radiation Therapy (SBRT) in Pelvic Lymph Node Oligometastases.

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  • Phase II trial of paclitaxel in patients with soft-tissue sarcoma.

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    pub_type: 临床试验,杂志文章

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    pub_type: 杂志文章

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    pub_type: 杂志文章,多中心研究

    doi:10.3109/07357900902918460

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    更新日期:2010-03-01 00:00:00

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    pub_type: 杂志文章

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    更新日期:2011-01-01 00:00:00

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