There are a number of key issues to consider when planning delivery of antineoplastic agents:
- Tumour burden: the larger the tumour, the greater the likelihood of the development of metastases.
- Tumour growth rate: the more rapidly growing the cancer, the more responsive its cells are to cytotoxic therapy.
- Tumour cell heterogeneity: increases the risk for the development of resistance.
- Tumour location.
- Hormone receptor status.
- Blood supply to the tumour.
The blood-brain barrier is a cellular structure inhibiting various substances from entering the brain, protecting both the brain and the cerebrospinal fluid from harmful agents.15
- Performance status: those with a better status may have a smaller tumour burden, and better ability to tolerate and respond to cytotoxic therapy. Cancer treatment centres use performance status as a prognostic indicator. Additional factors include stable weight, absence of concomitant illnesses, and optimal symptom management.
- Reduced immunity and weight loss decreases the individual's tolerance to treatment effects. If dose reductions and treatment delays are a result, tumour cells have a chance to develop resistance.
- Circadian rhythm refers to routine fluctuations in the biological functions of living creatures. These variables may affect drug absorption, metabolism, distribution, and elimination, and may be controlled to allow for intensification of drug dosages, and the reduction of side effects of being treated with cytotoxic drugs.2 For example, administering Fluorouracil in the evening may assist in reducing toxicities as the cells of the gastrointestinal system and the bone marrow are most actively dividing during the first half of the day.8
Single-agent therapy was often used in the early history of cancer chemotherapy. The major disadvantages of single-agent therapy led to clinical trials, starting in the 1960s, with combinations of drugs. Some of these disadvantages were:7
- poor success at achieving long-term remissions
- development of resistance to further drug therapy - the most common reason for treatment failure
- severe or lethal toxicities when given in doses adequate to eradicate the tumour.
With a few exceptions, combination therapy has replaced single-agent therapy in the medical management of cancer. Combinations of agents have been associated with less likelihood of resistance, increased fractional cell kill, and improved response rates. Principles underpinning the selection of agents within combination therapy include:1
- all drugs used should be of proven value in the disease they are intended to treat
- agents should have different modes of cytotoxic action
- if possible, the dose-limiting toxicities of the chosen agents should be different.
Describe the physiology of the blood-brain barrier.
Outline the implications of the blood-brain barrier for cancer control efforts.
Outline common methods of assessing an individual's performance status pre-treatment.
Define the term 'dose intensity'.
Discuss the implications of dose reduction and treatment delays on dose intensity.
Provide evidence based examples of the impact dose intensity has on a person's outcomes.
Discuss the rationale for continuous infusional and intermittent antineoplastic therapy.
Provide three examples of how an individual's hormone receptor status impacts on treatment determination.