Chemotherapy is administered in a variety of care settings. The majority of cancer patients receive systemic chemotherapy in an ambulatory care setting or in a day care unit designed to care for patients requiring lengthy infusions. Few individuals actually require hospitalisation for chemotherapy despite the fact that treatment regimens are currently more aggressive and dose-intensive in nature. Hospital admission is generally reserved for patients who require intensive monitoring or are acutely ill. The shift to outpatient ambulatory care services has grown out of the need for more efficient and economical health care delivery systems as hospitals cope with increases in managed care and capitation. Managed care is rapidly replacing fee-for-service in all aspects of the healthcare delivery system. The anti cancer drugs are known to be mutagenic, teratogenic and carcinogenic. Additionally, exposure has been reported to result in rashes, skin discolourations, scarring, blurred vision and dizziness.

Why protection is required?
Exposure to cytotoxic drugs is known to be potentially hazardous to one's health. The potential risk stems from the knowledge that some cytotoxic drugs are proven carcinogens and a number of studies monitoring hospital staff who were involved in preparing or giving these agents have demonstrated chromosomal abnormalities and excretion of mutagenic products in the urine. The abnormalities disappeared once exposure ceased and the actual amount of drug absorbed was extremely small. Nevertheless it has been argued that prolonged contact in this way could increase the chance of later developing a cancer. It is important to stress that this is only a theoretical possibility and that there is, as yet, no definite link between previous professional contact with cytotoxic and subsequent development of cancer. Even so, the possibility of a long-term hazard has to be taken seriously. This attention has produced detailed policy documents, spelling out the necessary precautions. Cytotoxic drugs may enter the body by three possible routes:
- Inhalation (when an aerosol or airborne dust is produced)
- Ingestion
- Skin contact
These are most likely to occur with injectable agents during either their preparation or administration. Therefore, to prevent the risk, adequate precautions must be taken by a pharmacist while admixturing chemo drugs.

Cytotoxic drug and personal safety
Class II cabinets are part-recirculation laminar airflow enclosures with HEPA filtration of exhaust air and an air barrier at the work opening. Separate fan/HEPA filter systems are provided for exhaust and laminar air flow. An inflow of room air into a full-width grille in the work opening creates an air barrier. A quantity of air, equal to that of the barrier air, is exhausted to the room via a second HEPA filter. Vertical laminar airflow is recirculated within the work zone to provide product protection. Class II cabinets combine the levels of protection afforded by class I cabinets and laminar flow cabinets for product protection. Biological safety cabinets are unsuitable for use with cytotoxic drugs and other toxic chemicals as these materials cannot be deactivated by fumigation. Aerosols of the materials, which are recirculated within the cabinet, contaminate fans and internal plenums. Therefore, if used for handling such materials, cabinets suffer permanent contamination of internal surfaces. This precludes safe internal maintenance. Cytotoxic drug safety cabinets are similar to class II cabinets in terms of operator and product protection. They also overcome the problem of protecting maintenance personnel by locating the exhaust filter under the work surface. They provide personnel, environmental and product protection.

Precautions during the admixture of cytotoxic drugs
Although adequate facilities for drug preparation are essential, the key to reduce the risk of exposure follows these points:
1. Wear latex powder free long cuff gloves while preparing chemotherapy drugs. Wear a gown that is low or non-permeable, long sleeve, cuffed and solid fronted and use aerosols free mask.
2. Work over a suitable container to prevent the spread of any spillage.
3. Prevent high pressure being generated inside sealed vials - when fluids are introduced an equivalent volume of air should be withdrawn or a venting needle with a hydrophobic filter (to prevent aerosol formation) may be used if available.
4. Ampoules should be directed away from the face and covered with a suitable pad or cotton when broken open.
5. Diluent fluids should be introduced slowly into open-ended ampoules or vials, running it down the vessel wall and ensuring the drug powder is moist before shaking.
6. When excess air is expelled from a filled syringe it should be exhausted into a pad and not straight into the atmosphere.
7. If excess drug is to be expelled from a filled syringe it should be removed first and sterile cotton wool placed over the end of the syringe to prevent possible scatter of aerosol droplets.
8. Luer lock fittings should be used in preference to push connections on syringes, tubing and I.V. sets.
9. Label all prepared bottles (It is mandatory).
10. Admix all cytotoxic drugs in class II biological safety cabinet (laminar air flow) that meets standards and it is inspected appropriately.
11. Check the reconstitute or diluents for the particular drug and the concentration in which it is to be reconstituted.

Checklist before preparing the cytotoxic drugs
* Name of the drug, company name, active salt, strength and expiry date
* Patient name, age and patient ID number
* Number of chemotherapy cycle
* Approximate cost of the drug
* Drug delivery route and access devices
* Solvent and its concentration in which it is to be mix
* Infusion or diluent fluids (D5%W / NS / RL / DNS) with which to be mixed
* Availability of drug delivery access
* Cross marking of the pack and label of the vial / ampoule
* Pre medication as prescribed is given
* Drug dose according to body surface area / body weight

Disposal of waste materials
All the waste materials like syringe, needle, mask and gloves should be disposed carefully in cytotoxic disposal bags. Changes of gloves and mask should be done after each admixture process. The syringes should also change after each drug admixing. A standard procedure is to be made and followed for disposals of waste materials. The disposal bags should print with cytotoxic drug.
Cytotoxic waste is highly hazardous and should never be land filled or discharged into the sewerage system. Disposal options include the following:
Return to original supplier: Safely packaged but outdated drugs and drugs that are no longer needed should be returned to the supplier. This is currently the preferred option for countries that lack the facilities for incineration. Drugs that have been unpacked should be repackaged in a manner as similar as possible to the original packaging and marked "outdated" or "not for use".

Incineration at high temperatures: Full destruction of all cytotoxic substances may require temperatures up to 1200°C; Incineration at lower temperatures may result in the release of hazardous cytotoxic vapours into the atmosphere. Modern double-chamber pyrolytic incinerators are suitable, provided that a temperature of 1200°C with a minimum gas residence time of 2 seconds or 1000°C with a minimum gas residence time of 5 seconds can be achieved in the second chamber. The incinerator should be fitted with gas cleaning equipment. Incineration is also possible in rotary kilns designed for thermal decomposition of chemical wastes, in foundries, or in cement kilns, which usually have furnaces operating well in excess of 850°C. Incineration is most common by municipal incinerators, in single-chamber incinerators or by open-air burning is inappropriate for the disposal of cytotoxic waste.

Chemical degradation: Chemical degradation methods, which convert cytotoxic compounds into non-toxic/non-genotoxic compounds, can be used not only for drug residues but also for cleaning of contaminated urinals, spillages, and protective clothing. The methods are appropriate for developing countries. Most of these methods are relatively simple and safe; they include oxidation by potassium permanganate (KMnO4) or sulphuric acid (H2SO4), denitrozation by hydro bromic acid (HBr), or reduction by nickel and aluminium. The International Agency for Research on Cancer* (IARC) may be contacted for further information.

It should be noted that neither incineration nor chemical degradation currently provides a completely satisfactory solution for the treatment of waste, spillages, or biological fluids contaminated by cytotoxic agents. Until such a solution is available, hospitals should use the utmost care in the use and handling of cytotoxic drugs.
Where neither high-temperature incineration nor chemical degradation methods are available and where exportation of cytotoxic wastes for adequate treatment to a country with the necessary facilities and expertise is not possible, encapsulation or inertization[u1][u2] [u3]may be considered as a last resort.

General principles of handling and disposals
* Dispose of all sharps, containers, and cytotoxic waste according to appropriate procedure in a hazardous waste poly bag
* Do not clip or recap needles. Discard the needle-syringe unit into a convenient and appropriately labelled, puncture-proof container
* Discard all gauze, tubing, bags, bottles, etc in appropriately labelled bags and seal. Remove gown and gloves and discard in a similar manner
* Wear latex powder free gloves while disposing chemotherapy drugs. Wear a gown that is low or non-permeable, long sleeve, cuffed and solid fronted and use aerosols free mask
* Clean up spills using available chemicals and disposable towels or sponges. For large spills, double gloving is recommended
* If direct exposure occurs, immediately rinse the area with running water. For eye exposure, rinse with an eye wash solution or sterile saline
* Report all episodes of drug exposure to concerned physician immediately
* Wash face & hand completely with running water

Management of spillage of cytotoxic drugs
The spillage of cytotoxic drugs should be done with care. It shouldn't clean in the same way as other drugs. A specific procedure must be maintained for spillage and it should be treated appropriately. On spillage of cytotoxic drugs it should neutralise with appropriate chemical solution and then wash with detergent and water immediately. Some specific inactivating chemicals for cytotoxic drugs are given below:

 Spill kit: The admixture room should have a spill kit with the following items:
1. Phosphate Buffer pH 7.4
2. DMSO 100%
3. Hypochlorite Ointment FNA 0.25% (Formely Euosol)
4. Sodium Thiosulphate 10%
5. Sodium Carbonate Solution 3%
6. Sodium Hypochlorite 5%
7. 0.1N Hydrochloric Acid
8. Alcohol 70%
9. Powder Free Gloves - 2 pairs
10. Aerosols Free Mask - 1
11. Absorbent Towel - 2, 12"x12"
12. Scoop & Brush -1 set
13. Eye Glass -1
14. Cytotoxic Disposal Poly Bag -1
15. Gown Poly Coated -1
16. Shoe Covers -1 pair
17. Head Cap -1

Conclusion
This review study reveals that the cytotoxic admixture should be done by a proper procedure in all the cancer institutes. This is the area where the pharmacist can utilise his knowledge of pharmaceutics. Working with cytotoxic drugs requires adequate knowledge and skill. Chemo drugs are very toxic for which proper care and precautions is to be taken while handling, preparing, administering and disposing. Working as an oncology pharmacist is an image for pharmacist to be considered in a healthcare team to fight against the killing disease. This review article would be a great help for the pharmacist who is involved in this practice or those who wants to start career in this field. This paper gives information about practical guidelines for cytotoxic preparations and handling process. The ability of the oncology pharmacist to recognise time as a critical factor in cancer therapy is important as well when working through the financial concerns.

Review of key points
* Cytotoxic agents are mutagenic, teratogenic and carcinogenic
* Direct exposure to agents can occur during admixture, administration, handling and during disposals
* Exposure to cytotoxic occurs through inhalation, ingestion, or absorption
* The use of personal protective equipment (PPE) greatly minimises risk of exposure - It's your life and your health!
* It is recommended that pregnant employees be informed of potential risks and, if necessary, reassigned to other duties
* Always follow a guideline for chemotherapy procedure

References:
1. Oncology Nursing Society: ONS Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, Oncology Nursing Society Press; 1999.
2. Rutherford C: Position Paper-Administration of Antineoplastic Agents: J Intraven Nurs; 15:8-9, 1992.
3. American Society of Hospital Pharmacists: ASHP Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs, Am J Hosp Pharm; 47:1033-1049, 1990.
4. American Society of Hospital Pharmacists: Safe Handling of Cytotoxic and Hazardous Drugs Study Guide. Bethesda MD, American Society of Hospital Pharmacists; 1990.
5. Johan Vandenbroucke, Hugo Robays : How to Protect Environment and Employees Against Cytotoxic Agents the Ghent Experience, J Oncol Pharm Practice; Vol. 6, No 4, 146-152, 2001.
6. Catherine Wick, Matthew H. Slawson, James A. Jorgenson and Linda S. Tyler: Using a Closed System Protective Device to Reduce Personnel Exposure to Antineoplastic Agents, Am J Health-Syst Pharm; Vol 60, Nov 15' 2003.
7. Kiffmeyer TK, Kube C, Opiolka S etal.: Vapour Pressure, Evaporation Behavior and Air Borne Concentration of Hazardous Drugs; Implication for Occupational Safety, Pharm J 2000, 268:331-7.
8. Sessink PJM, Wittenhorst BCJ, Anzion RBM, Rob RP : Exposure of Pharmacy Technicians to Antineoplastic Agents: Reevaluation After Additional Protective Measures, Arch Environ Health, 1997; 52:240-244
9. American Society of Health-System pharmacists: Drug Information 2004
10. The American Cancer Society: Cancer Facts and Figures 2002, www.cancer.org
11. www.cancersourceRN.com
12. Safe Management of Wastes from Health Care Activities: 1999 WHO, www.who.int/cytotoxic waste management

* International Agency for Research on Cancer, Unit of Gene-Environment Interactions, 150 Cours Albert-Thomas, 69372 Lyon Cedex 08, France.

(Concluded)
The authors are with Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110044.