Assessment of exposure risk of irinotecan and its active metabolite,SN-38,through perspiration during chemotherapy

Abstract

Background

Irinotecan (CPT-11) is the key drug used in chemotherapy for many malignant tumors. CPT-11 has cholinergic activity and induces perspiration during intravenous administration. In this study, concentrations of CPT-11 and its active metabolite, SN-38, released during perspiration were measured and risk of exposure of these drugs was assessed.

Method

Beads of sweat were collected using a dropper from four patients undergoing a chemotherapy regimen involving intravenous administration of CPT-11. The concentrations of CPT-11 and SN-38 in sweat were measured using liquid chromatography tandem mass spectrometry.

Result

Chemotherapy regimens were capecitabine and irinotecan plus bevacizumab (n = 1), CPT-11 monotherapy (n = 1), and oxaliplatin–irinotecan–leucovorin–5-fluorouracil (n = 2). Uridine diphosphate-glucuronosyltransferase 1A1 phenotypes were *6 homo-type (n = 1), *6 hetero-type (n = 1), and wild type (n = 2). CPT-11 dose was 292.3 ± 75.5 mg/body weight (mean ± standard deviation). CPT-11 was detected in sweat secreted by all the four patients, and its mean (±standard deviation) concentration was 252.6 (±111.9) ng/ml. SN-38 was detected in only one of the patients who received oxaliplatin–irinotecan–leucovorin–5-fluorouracil treatment and who had the wild-type uridine diphosphate-glucuronosyltransferase 1A1 phenotype at a concentration of 74.37 ng/ml.

Conclusion

CPT-11 and SN-38 are detected in sweat released during intravenous CPT-11 administration. Beads of sweat or linen clothes that absorb the sweat might be the source of CPT-11 and SN-38 exposure.

Keywords

Exposure irinotecan occupational SN-38 sweat

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References

Fujita

Kubota

Ishida

et al.

Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. World J Gastroenterol 2015; 21: 12234–12234.

Fukuoka

Niitani

Suzuki

et al.

A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. J Clin Oncol 1992; 10: 16–20.

Kawato

. Inhibitory effect of CPT-11, a derivative of camptothecin, on acetylcholinesterase, and its binding ability to acetylcholine receptors. Kiso to Rinsho 1990; 24: 7407–7412. (in Japanese).

Abigerges

Chabot

Armand

et al.

Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol 1995; 13: 210–221.

National Institute for Occupational Safety and Health. Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. DHHS Publ No. 2004-165, Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.

American Society of Health-System Pharmacist. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm 2006; 63: 1172–1193.

Chen

Peer

Alfaro

et al.

Quantification of irinotecan, SN38, and SN38G in human and porcine plasma by ultra high-performance liquid chromatography-tandem mass spectrometry and its application to hepatic chemoembolization. J Pharm Biomed Anal 2012; 62: 140–148.

National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2016.

van Ark-Otte

Kedde

van der Vijgh

et al.

Determinants of CPT-11 and SN-38 activities in human lung cancer cells. Br J Cancer 1998; 77: 2171–2176.