Treatment of Advanced Malignancies with High-Dose Acetaminophen and N-Acetylcysteine Rescue
作者:
KobrinskyNathan L.,
HartfieldDawn,
HornerHeather,
MaksymiukAndrew,
MinukGerald Y.,
WhiteDavid F.,
FeldsteinThomas J.,
期刊:
Cancer Investigation
(Taylor Available online 1996)
卷期:
Volume 14,
issue 3
页码: 202-210
ISSN:0735-7907
年代: 1996
DOI:10.3109/07357909609012140
出版商: Taylor&Francis
数据来源: Taylor
摘要:
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 NA C rescue was conducted on 19 patients with advanced cancer. HDA C was escalated from 6 to 20 g/m2PO 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.
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