Chemotherapy Flashcards
chemotherapy mechanism of action
- Most agents target DNA either directly or indirectly.
- Chemotherapeutic agents are preferentially toxic towards actively proliferating calls. Tumours which divide rapidly, with short doubling times, usually respond best to chemotherapy.
There are other factors that determine a tumour’s chemosensitvity. For example, although cytotoxic drugs consistently cause DNA damage, tumour cells differ with regard to their response (death or recovery) to that damage.
chemotherapy indications list
- neoadjuvant
- primary
- adjuvant
- palliative
- curative
- prophylactic
definition and aims of neoadjuvant chemotherapy
- Pre-operative treatment of an operable tumour before definitive surgical intervention.
- aims of this are to make the tumour smaller, to allow less radical surgery, while at the same time treating occult micro metastases.
This approach is established for osteosarcoma and is being tested in clinical trials for other malignancies, such as breast cancer. This is therefore treatment which aims to increase cure rates.
definition and aims of primary chemotherapy
Initial chemotherapy for a tumour that is inoperable or of uncertain operability, where a reduction in the tumour bulk in a pre-defined manner may make surgery with curative intent feasible. This is therefore treatment which may increase cure rates.
adjuvant chemotherapy definition and aims
The use of chemotherapy following a complete macroscopic clearance at surgery. Chemotherapy in this setting treats the occult microscopic metastases which we know usually lead to relapse after surgery for lymph-node positive disease (e.g. breast cancer and colorectal cancer). This is therefore treatment which increases cure rates.
palliative chemotherapy definition and aims
This is treatment to alleviate symptoms and in some cases prolong life in patients who cannot be cured.
Chemotherapy given in the palliative setting has to be a carefully balanced decision so that the patient’s quality of life is not made worse by the treatment.
It may be justified to give second or third line chemotherapy if the disease remains chemo-sensitive (e.g. breast cancer, ovarian cancer, colorectal cancer).
curative chemotherapy aims
In some malignancies there is still a real chance of a cure even if there is metastatic disease at presentation (e.g. germ cell tumours, Hodgkin’s disease, Non-Hodgkin’s lymphoma and many childhood cancers). This justifies the use of more intensive treatment associated with greater toxicity.
prophylactic chemotherapy definition and example
Hormonal treatments may be given before overt malignancy appears. For instance tamoxifen may be used for in-situ breast cancer before invasive carcinoma is recognised
Cytotoxic chemotherapy is most commonly given as a combination of different drugs. This is because:
- Different classes of drugs have different actions and may kill more cancer cells together by imparting several sub-lethal cell injuries than the sum of the cells they can kill when given individually (‘synergism’).
- There is less chance of drug-resistant malignant cells emerging.
- When drugs with different sites of toxicity are combined, dose can be maintained for each drug.
Single-agent chemotherapy may also be appropriate, especially in the palliative setting.
Most chemotherapy is given cyclically to allow normal cells to recover from the toxicity of treatment. The cells usually affected by chemotherapy at standard doses are haematopoietic stem cells and the lining of the GI tract, producing low blood counts (‘myelosuppression’) and mucositis. Giving the treatment every 3-4 weeks allows these cells to recover.
Theoretically any cycle of chemotherapy will only kill a proportion of the tumour cells. Therefore repeated cycles are required to get tumour clearance. However, there is no advantage in giving endless cycles of chemotherapy, as this does not prevent resistance emerging and increases toxicity; many treatments are maximally effective after a 6-month course.
which treatment can be given as outpatients and which treatments require inpatient
Conventional doses of drugs are those known to be effective against the particular malignancy and which, in the majority of patients, cause tolerable side effects. Many of these treatments can be given in an out-patient setting.
“High dose” treatments produce toxicity that is much greater. Such treatments require particularly specialized supportive care or they are lethal; including bone marrow support with growth factors, or often ‘rescue’ of the bone marrow using the infusion of previously harvested blood stem cells or bone marrow. The toxicity of this treatment is justified only when longterm survival or cure are possible, which is only the case in relatively few cancers, such as Hodgkins disease and Ewings Sarcoma.
in which cases is prolonged chemotherapy to maintain remission appropriate? when is it inappropriate?
The use of prolonged chemotherapy to maintain a remission has little demonstrated advantage in solid tumours, as resistant clones soon develop and toxicity increases.
In childhood leukaemia 18 months maintenance chemotherapy following the induction of a complete remission is central to modern treatment.
Advantages and disadvantages of giving chemotherapy orally? Which drugs are available orally?
- freeing the patient from lengthy hospital visits and invasive procedures.
- It doesn’t necessarily reduce toxicity however as the drug is still cytotoxic and regular review is almost always still required.
- Only a minority of drugs including cyclophosphamide, etoposide, capecitabine and tamoxifen are available orally.
- Variations in the levels of drug circulating based upon whether and when the drug is taken can be problematic.
how is the majority of chemotherapy delivered?
Systemic delivery:
Most chemotherapy is given intravenously as bolus injection or short infusion.
Some chemotherapy may be given as a continuous infusion via a central venous line, either peripherally placed or tunneled under the skin to reduce the chances of infection.
