* Correspondence Annette N. Smith, Department of Clinical Sciences, Wilford & Kate Bailey Small Animal Teaching Hospital, 1220 Wire Rd, College of Veterinary Medicine, Auburn University, AL 36849‐5540. Email: ude.nrubua@03htims
Received 2018 Jan 18; Revised 2018 Jan 22; Accepted 2018 Jan 22.Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
The purpose of this report is to offer a consensus opinion of ACVIM oncology diplomates and technicians on the safe use of cytotoxic chemotherapeutics in veterinary practice. The focus is on minimizing harm to the personnel exposed to the drugs: veterinary practitioners, veterinary technicians, veterinary staff, and pet owners. The safety of the patient receiving these drugs is also of paramount importance, but is not addressed in this statement. Much of the information presented is based on national recommendations by Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, United States Pharmacopeia, and other published regulations. These directives reflect an abundance of caution to minimize exposure to medical personnel, but large‐scale studies about the consequences of long‐term occupational exposure are not available in veterinary medicine. Challenges in the delivery of optimal treatment safely and economically to veterinary patients in general practice without access to a veterinary oncologist or other specialist, because of costs or proximity, remain.
Keywords: cancer, drugs, NIOSH, safetyBSC biologic safety cabinet CSTD closed‐system transfer devices HD hazardous drugs NIOSH National Institute for Occupational Safety and Health OSHA Occupational Safety and Health Administration PPE personal protective equipment SDS safety data sheets RCRA Resource Conservation and Recovery Act USP United States Pharmacopeia
As use of cytotoxic chemotherapy in veterinary practice increases,1, 2, 3 there is a greater risk of cytotoxic exposure in the workplace and the patient's home environment. Increasing popularity in the use of continuous low‐dose PO chemotherapy (“metronomic” chemotherapy) and daily or every‐other‐day small molecule inhibitor treatment also increases the risk of exposure to clients.
Handling of cytotoxic drugs has been classified as an occupational health hazard according to a National Institute for Occupational Safety and Health (NIOSH) alert, first published in 2004 and most recently updated in 2016.4 Such drugs are carcinogenic, mutagenic, teratogenic, abortifacient, and increase the risk of stillbirth.5, 6, 7, 8 Some of this information has been derived from in vitro studies, animal studies, and from studies in pregnant women receiving chemotherapy for their own malignancies, but adverse effects still might be seen at lower levels of exposure. Compared to intermittent high‐dose exposure, chronic low levels of cytotoxic chemotherapy exposure actually may have increased risk, because cytotoxic effects are less likely to occur with similar mutagenic effects.9 Veterinary small molecule inhibitors, although often not considered “classical” chemotherapy agents, carry similar risks, according to package inserts (https://www.zoetisus.com/products/dogs/palladia/index.aspx). Current targets are associated with angiogenesis, and treatment with these agents could harm a growing fetus. They should be handled as other cytotoxic drugs.
Human healthcare workers (eg, pharmacy employees, nurses) handling chemotherapeutics have been found to have variably increased chromosomal aberrations compared to the general population,9, 10, 11, 12, 13, 14, 15, 16 as well as urinary excretion of these drugs or their metabolites,17, 18 which could lead to similar reproductive complications found in cancer patients treated with cytotoxic drugs.19, 20, 21, 22, 23 In fact, some large studies5 and a meta‐analysis24 have shown an incremental increased risk of infertility and early pregnancy loss with occupational exposure to chemotherapeutics. Chromosome changes appear to be exposure‐ and drug‐dependent, with high‐volume practice and alkylators being associated with the most abnormalities.10 Additionally, the chance of developing some cancers might be increased.21, 23, 25 As a caveat, most of the studies included in the meta‐analysis were performed before the widespread use of closed‐system transfer devices (CSTD). Various methods used to detect abnormalities, lifestyle factors, amount of exposure to cytotoxic drugs, and variable use of safety measures impact the usefulness of these studies in attributing causation to these health risks. The addition of protective measures such as biologic safety cabinets (BSCs), CSTDs, and personal protective equipment (PPE) markedly decreases, but does not always eliminate, evidence of drug contamination.16, 26, 27
In veterinary medicine, several studies have been performed to investigate occupational risk in reproductive outcomes and cancer development. However, chemotherapy use and exposure have not been specifically investigated related to these outcomes. A 1998 study of 3000 female veterinary graduates showed both a decreased risk of preterm delivery and a decreased risk for small‐for‐gestational age births compared to the general population.28 In a review of several studies examining the cause of death in veterinarians, an increased risk was found for the development of multiple myeloma (6 cases out of 12 000), and a decreased risk for lung cancer, but overall there was a similar risk of cancer as in the general population and no conclusion about specific occupational exposures could be made.29 Reportedly, 71% of veterinary practices in the United Kingdom use cytotoxic drugs, indicating that practitioners do need to be aware of the use of protective procedures when using chemotherapeutics.30 In a 2009 survey of 93 practices in Hampshire,31 half of which used cytotoxic drugs, 100% reported compliance with staff training, exclusion of pregnant workers, waste management, and instructions to clients about precautions. However, none had a designated BSC, and only 82% used PPE. In a survey of Canadian veterinary practice, 30% of general practitioners and 22% of academic veterinarians reported using chemotherapeutics.32 Mixed or small animal practitioners made up 91% of the private practice population and equine practitioners 8.6%. In 8% of general practice veterinarians, accidental exposures to cytotoxic drugs were reported. Academic veterinarians using chemotherapeutics were mostly small animal or mixed practitioners (47%), although a larger proportion of equine veterinarians using chemotherapeutics was found in academia (35%). No accidental exposures were reported in this population. In the Netherlands, a 2006 study found frequent contamination of the veterinary practice environment, including gloves of personnel administering chemotherapy, surfaces of preparation and administration areas, floors, and door handles.33 In a review of an American veterinary teaching hospital in 2010, surface contamination was found in 10% of swabs within the preparation area only, and 60%‐70% compliance with safety procedures regarding the use of PPE was reported.34
The risk to clients while caring for their pets with cancer or administering cytotoxic drugs also is poorly defined. Some contamination of the environment, and potential exposure to family members or caregivers occurs when people are receiving chemotherapy.33, 35 Guidelines for safe handling of PO chemotherapeutics in human practice have been compiled, attempting to limit potential harms.36 In veterinary medicine, some environmental contamination also has been documented,37 and similar precautions should be taken by clients handling veterinary cancer patients undergoing chemotherapy and administering drugs at home to their pets.38, 39
Because chemotherapy drugs usually have a low therapeutic index, inappropriate administration increases risks of exposure to personnel, as well as the risk of adverse events for the patient. Evaluation and suggestions in this regard are beyond the scope of this consensus statement, but some guidelines have been included that also impact the safety of those administering drugs. The European consensus statement on chemotherapy use recommends that these drugs should have proven efficacy before administration, recognizing that most are used in an off‐label fashion. Acknowledging that practitioners other than oncologists do administer these drugs, at a minimum, consultation with a veterinary oncologist to determine the risks versus benefits to the patient is strongly recommended. The reader is referred to the following resources regarding patient safety:
Biller B, Berg J, Garrett L, et al. 2016 AAHA oncology guidelines for dogs and cats. J Am Anim Hosp Assoc. 2016;52:182–204.
Steffy‐Morgan JD. Chemotherapy: chemotherapy administration. In: Henry CJ, Higginbotham ML, eds. Cancer Management in Small Animal Practice. MO: Saunders Elsevier Maryland Heights; 2010:114–118.
Several states now mandate that veterinary hospitals comply with NIOSH guidelines40 regarding hazardous drugs (HD). The first was the state of Washington in April 2011, closely followed by California in 2013 and North Carolina in 2014. The United States Pharmacopeia (USP) has updated guidelines (Chapter 800) that are scheduled to be implemented in 2019.
Washington State Laws & Guidelines: