INTRODUCTION TO CHEMOTHERAPY

Chemotherapy refers to the treatment of cancer using specific drugs that selectively destroy malignant cells.

Chemotherapy primarily damages rapidly dividing cells and will impact both normal and malignant cells.

Chemotherapy is prescribed when systemic treatment for cancer is required. This may be for systemic cancers such as lymphoma or for cancers with a high risk of metastasis.

Chemotherapy agents are potentially mutagenic, carcinogenic and teratogenic and extra measures are necessary to ensure staff and patient safety. 

The health effects of exposure to cytotoxic drugs are not fully understood however minimising even low-level exposure is prudent.

Their packaging is marked with the cautionary symbols below to indicate the potential hazard to human health.

 

All staff should limit their exposure to cytotoxic agents. Immune-compromised, pregnant or breastfeeding staff should not be involved in chemotherapy administration, preparation or the handling of cytotoxic patients or drugs or cleaning of cytotoxic areas or equipment.

Veterinary clinics are required to maintain a safe working environment without risks to human health. 

HOW DOES CHEMOTHERAPY WORK?

Chemotherapy agents interfere with progression through the cell cycle and thus disrupt cellular replication.

Most drugs interfere with DNA replication (S phase of the cell cycle) or cell division (M phase of the cell cycle) resulting in cell death.

 

Chemotherapy drugs are classified as either cell cycle phase specific or cell cycle phase non-specific.

Chemotherapy agents are also classified by their mechanism of action:

  • Alkylating agents (e.g. melphalan, cyclophosphamide, chlorambucil)
  • Antimetabolites (e.g. cytarabine, methotrexate)
  • Antitumour antibiotics (e.g. doxorubicin)
  • Vinca alkaloids (e.g. vincristine, vinblastine)
  • Platinum agents (e.g. carboplatin)
  • Nitrosureas (e.g. lomustine)

Chemotherapy agents disrupt cellular replication in both normal and malignant cells however normal cells can often repair minor damage and survive.

Tumours with fewer cells tend to be more effectively treated by chemotherapy. As tumours increase in size, there are generally fewer cells dividing (more are in the resting phase of the cell cycle) and chemotherapy is less effective.

Repeated doses of chemotherapy are used to reduce the overall tumour burden. In some cases, different drugs with different mechanisms of action are used.

Conventional chemotherapy is administered at the maximum tolerated dose (MTD). This is the highest dose that can be administered without causing unacceptable side effects.

TERMINOLOGY

Induction: initial therapy that aims to significantly reduce the number of cancer cells (ideally will lead to complete remission).

Maintenance: prolonged (often lower dose) chemotherapy that aims to extend the duration of remission.

Adjuvant therapy: treatment used in conjunction with other anti-cancer therapy (usually surgery) that aims to treat micrometastases and/or reduce the likelihood of tumour recurrence.

Neo-adjuvant therapy: the use of chemotherapy agents to reduce the size of a tumour before surgery.

Rescue therapy: chemotherapy given after the failure of other agents.

SMALL MOLECULE INHIBITORS

Veterinary small molecule inhibitors (e.g. toceranib, masitinib) are not technically classed as chemotherapy however they carry similar risks to health and safety.

Small molecule inhibitors act by interfering with signalling processes that trigger the cell cycle and cell proliferation.

METRONOMIC CHEMOTHERAPY

Metronomic chemotherapy is low dose chemotherapy given at frequent, regular intervals (usually daily or every other day).

Metronomic chemotherapy acts by antiangiogenic and immunomodulatory activity to potentially slow the progression of some tumour types.

The same precautions should be taken when handling metronomic chemotherapy and patients as for other chemotherapy drugs.

Exposure to cytotoxic agents can occur via the skin, mucosa, inhalation, ingestion or sharps injury during:

  • Drug transport, preparation and administration
  • Cytotoxic drug spill cleaning
  • Handling of contaminated waste, bedding and excretions
  • Contact with contaminated surfaces and drug packaging

NEXT LESSON…. SAFETY DURING CHEMOTHERAPY PREPARATION