Chemotherapy agents are genotoxic, mutagenic and teratogenic therefore, unsurprisingly, their use is considered an occupational health hazard. The use of these agents appears to be increasing due to demand from clients wishing to treat cancer in their pets, therefore, the number of events carrying an exposure risk is on the rise. In addition to the increased use of ‘conventional’ chemotherapy, innovative dosing strategies such as metronomic chemotherapy reduce the direct control that practices can exert over safe use (as clients are the primary administrators in this context). There is also increasing availability of novel agents such as small molecular c-kit inhibitors which are not chemotherapeutic in the conventional sense but may carry similar risks especially in relation to pregnancy and should, therefore, be handled as cytotoxic drugs. Considering these risks together, great care must be taken to provide appropriate education to staff and clients in order that exposure to these drugs can be avoided.

Appropriate indication for the use of chemotherapy

Given the potential risks associated with chemotherapy exposure, both to the patient and those involved in preparing and handling chemotherapy agents, they should only be prescribed when absolutely indicated (i.e. for histologically-confirmed diseases when the likelihood of response is considered high). Investigational use should be confined to controlled clinical trials.

Routes to exposure

Exposure can occur during the preparation, handling and administration of the agents, as a result of cleaning spills, and through contact with bodily fluids or excreta of patients treated with chemotherapy. The environment in which the patient is treated and housed after chemotherapy is at risk of contamination (both within the hospital and in the home). Therefore, practice staff, owners and subsequent users of administration spaces are all at risk of exposure in the event of contamination. Exposure may occur via direct skin contact, inhalation of aerosolized drug particles, ingestion or needle stick injuries.

Approaches to mitigate the risk of exposure

Practices should assess the suitability of their environment and staffing (both level and training) for chemotherapy administration. In some cases, the facilities or staffing levels or training may be unsuitable. In these instances patients should be referred. Similarly, veterinary surgeons should consider the suitability of patients and owners prior to starting treatment. This assessment is particularly relevant for oral medications as administration is not under the direct control of the veterinary surgeon and owners may become too relaxed about safety precautions.   The following guidance is provided to help minimize the risks associated with chemotherapy use.

Personnel and owners:

• The preparation and administration of cytotoxic drugs should only be undertaken by trained staff.
• Practices should develop standard operating procedures (SOPs) for preparing, handling and administering chemotherapeutic agents, and for managing potentially contaminated spaces after the administration of chemotherapy or following spills, and for housing treated patients. Staff should be trained in these SOPs with regular refreshers sessions held. Records of staff training should be kept. 
• Owners and staff (including cleaners, animal carers and veterinary professionals) involved in the care of animals being treated with cytotoxic drugs must be informed of:
  • - The risks of working with cytotoxic agents (to them as well as the patient)
  • - The potential methods for preventing aerosol formation and the spread of contamination 
  • - The proper working practices for a safety cabinet (if available)
  • - The instructions to clean contaminated spaces and spills
  • - The principles of good personal protection and hygiene practice.
• Pregnant and immunocompromised personnel should not be involved in the process of preparing and/or administering cytotoxic agents, caring for animals that have been treated with cytotoxic drugs or cleaning the areas with which these animals have come into contact. Employees should be made aware that the risk to a fetus may be highest in the first trimester of pregnancy; consequently, employees planning to conceive and/or are in the early stages of pregnancy should be assigned to other duties. It is the responsibility of the employee to warn their employers if they are pregnant, likely to become pregnant or are immunocompromised.

Equipment and facilities:

• All areas where cytotoxic agents are prepared and/or administered, or where animals who have received cytotoxic drugs are being cared for, should be identified by a clear warning sign. 
• Access to these areas should be restricted, ideally at all times, but at a minimum during chemotherapy preparation and administration. 
• No rest activities or food or drink consumption should be permitted in the preparation, administration or post treatment kennelling areas at any time. 
• There must be adequate materials for cleaning spilled cytotoxic agents (cytotoxic spill kit), clearly labelled and with associated use instructions, within the preparation and administration area(s). 
• Ideally, a negative pressure pharmaceutical isolator with externally ducted exhaust filters, which has been properly serviced and checked, should be used. If such an isolator is not available, then a suitably modified Class 2B Biological Safety Cabinet (BSC) may be used. 
• Regardless of whether a BSC is available, use of a needle-free closed or semi-closed system is mandatory to prevent aerosol formation, reduce the risk of stick injury and control exposure to carcinogenic compounds. Available systems include (but are not limited to): ChemoClave/Chemolock, Equashield, Onguard, PhaSeal and Spiros.

Preparation of cytotoxic drugs:

• Printed copies of preparation SOPs and drug data sheets should be available in the room in which the agents are to be prepared. 
• Where available, the ventilated cabinet should be used for all chemotherapy preparation. 
• If a BSC is not available, veterinary surgeons should consider acquiring pre-prepared patient specific doses of chemotherapy from a commercial company. 
• During preparation and administration, disposable chemoprotective personal protective equipment (PPE) should be worn by all involved staff. The PPE should include: 
  • - A chemotherapy impermeable full-length gown. The gown should have elasticated cuffs 
  • - Two pairs of chemotherapy impermeable (often nitrile) gloves. One seated underneath the cuff and one covering it entirely 
  • - Eye protection in the form of goggles or a face shield 
  • - Fitted respiratory protection is ideal and should be considered mandatory if chemotherapy is prepared outside of a BSC.
• The dosage of chemotherapy should be calculated, and the calculation checked by at least one colleague. 
• All essential supplies should be kept inside the BSC. Absorbent padding should be placed in the BSC under the chemotherapy draw area. 
• All administration consumables (tubing, fluid bags) should be prepared and primed outside the BSC prior to adding the chemotherapeutic agents (which should be done within the BSC). Heparinized saline should be avoided as it can interact with some chemotherapeutic drugs (e.g. doxorubicin/epirubicin). 
• Chemotherapy injection spikes rather than needles should be used for withdrawing liquid chemotherapy. 
• Manual handling of oral or topical medicines containing cytotoxic drugs should be avoided. Oral chemotherapy drugs should never be crushed or split. Several companies (e.g. BOVA, Chemopet, NOVA) supply compounded chemotherapy agents in various sizes suitable for different patients. This may be useful for drugs such as piroxicam, hydroxycarbamide, cyclophosphamide and lomustine. If reformulation is not possible, then adjusting the dosage regimen is often sufficient.
• When drug preparation is complete, the final product should be sealed in a plastic bag or other container for transport before it is taken out of the BSC. It should be clearly labelled with the drug name, patient name and dose. 
• All potentially contaminated materials should be discarded in special cytotoxic waste disposal containers, which can be opened without direct contact with hands/gloves (e.g. a foot pedal). Local regulations for the disposal of this waste should be followed. 
• The chemotherapy preparation space should be decontaminated and disinfected, and the outer pair of gloves discarded. 
• Once drug preparation is complete, the inner pair of gloves can be discarded. 
• There should be a clear procedure regarding how to handle cytotoxic drugs following an injection accident.

Administration of cytotoxic drugs:

• Prior to prescribing chemotherapy, the veterinary surgeon should make an assessment of the suitability of the patient to receive treatment (and be hospitalized should there be a significant adverse event). 
• Drug administration should take place in a quiet and calm environment with restricted entry during the process. The external side of the door should be labelled to warn other staff. Personnel administering chemotherapy should not be disturbed. 
• At the time of administration, the veterinary surgeon should again assess whether the patient is adequately calm and cooperative for safe administration. Anxious patients may benefit from the administration of mild anxiolytics prior to arrival at the clinic (e.g. trazodone, gabapentin). Fractious or exuberant animals should be sedated (with the owner’s consent). 
• Two suitably trained members of staff should be present with the patient throughout the administration process. This is especially important when using vesicant drugs such as vinca alkaloids (vincristine, vinblastine) or anthracyclines (doxorubicin/epirubicin). 
• A pre-administration checklist should be developed to confirm: 
  • - The correct patient identity 
  • - The blood results have been checked and are adequate for chemotherapy  
  • - The correct volume of drug has been accurately prepared 
  • - The catheter is has been placed and is functioning properly 
  • - The patient is calm and can comfortably be restrained for the expected duration of administration 
  • - All staff are wearing adequate PPE (as described in the preparation section, although a single pair of gloves is  acceptable). 
• Drugs should be administered safely using a needle-free system (such as those described above). 
• Drug administration should occur over a disposable absorbent pad (e.g. incontinence pad). 
• The tubing should never be removed from a fluid bag containing a hazardous drug, nor should it be disconnected at any other point in the system. The intravenous catheter, tubing and bag should be removed from the patient and discarded intact as a single unit when possible. A cytotoxic waste bin should be used. 
• The patient should be clearly labelled as a chemotherapy recipient (e.g. different coloured name tag). The chemotherapy injection site should be wrapped in a coloured dressing that identifies this procedure has occurred. 
• Hands should be washed with soap and water before leaving the drug administration area. 
• Procedures should be in place for dealing with any spillages that occur and for the safe disposal of waste. In the event of contact with skin or eyes, the affected area should be washed with copious amounts of water or normal saline. Medical advice should be sought if the eyes are affected.

Procedures for nursing patients receiving chemotherapy:

• Special wards or designated kennels with clear identification that the patients are being treated with cytotoxic agents is required. As well as kennel notices, different coloured bedding can be a helpful indicator. 
• Excreta (saliva, urine, vomit, faeces) are all potentially hazardous after the animal has been treated with cytotoxic drugs and should be handled and disposed of accordingly. 
• For hospitalized patients, the period of risk (i.e. the period during which the patient is expected to be excreting chemotherapeutic drugs or metabolites) should be clearly marked on the kennel and chemotherapy impervious PPE (such as disposable gloves and protective clothing) should be worn when carrying out nursing procedures (see the ACVIM small animal consensus statement (Smith et al., 2018) for more information on excretion periods). 
• All materials that have come into contact with the animal during the period of risk should be considered as potentially contaminated. 
• After the animal has left the ward, the kennel should be cleaned according to the chemotherapy specific cleaning protocol.

Guidelines for owners:

• All owners should be given written information about: 
  • - The potential hazards of cytotoxic drugs (to humans and treated pets) 
  • - The excretion period relevant to the drug(s) administered 
  • - How to deal with the patient’s excreta (saliva, urine, vomit, faeces). 
• If owners are to administer tablets themselves, then they should receive written information stating: 
  • - The PPE required 
  • - That oral chemotherapeutic agents should not be crushed or split. 
• Medicine containers should be clearly labelled with ‘cytotoxic contents’ warning tape. 
• Veterinary surgeons should: 
  • - Offer to provide suitable PPE 
  • - Confirm owners are using the provided PPE during subsequent consultations.

Cost and chemotherapy safety

Undoubtedly some of the mitigating measures described above will increase the cost of chemotherapy and, unfortunately, in some cases may make chemotherapy unaffordable. However, practices have legal responsibilities to safeguard their employees and the public, and veterinary professionals have a duty of care to their patients. Therefore, cost is not a reason for not following suitable safety procedures.

Further information

The guidance provided here is a summary of current best practice, but is subject to continual re-evaluation and, therefore, practices should review their approach from time to time. For further information, readers are encouraged to review the ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice (Smith et al., 2018). Safe handling of cytotoxic drugs in the workplace (hse.gov.uk/healthservices/safe-use-cytotoxic-drugs.htm) and the NIOSH guidance on Safe handling of hazardous drugs for veterinary healthcare workers (cdc.gov/niosh)

Reference

Smith AN, Klahn S, Phillips B et al. (2018) ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice. Journal of Veterinary Internal Medicine 32(3), 904–913