Chemotherapy Flashcards
Why do 60-70% of cancers need systemic treatment such as chemotherapy?
Patient’s die from systemic spread of disease
What type of chemotherapy is neoadjuvant?
Chemotherapy before definitive surgical intervention
What are the aims of neoadjuvant chemotherapy?
To make the tumour smaller to allow less radical surgery, while also treating small occult metastases
In what cancer is neoadjuvant chemotherapy established as treatment protocol?
Osteosarcoma, being trailed for breast cancer
Discuss primary chemotherapy
Initial chemotherapy for a tumour that is inoperable
Reduction in tumour may make surgery with curative intent possible
Does primary chemotherapy increase cure rates?
Yes
What is the use of adjuvant chemotherapy?
Chemotherapy after complete macroscopic clearance at surgery
Chemotherapy in this setting treats the occult microscopic metastases
why is adjuvant chemotherapy important?
Treats occult microscopy metastases that have been proven to lead to relapse after surgery for lymph-node positive disease (e.g. breast or colorectal cancer)
This treatment increases cure rates
Discuss palliative chemotherapy
This aims to improve symptoms and prolong life
The treatment must not worsen a patient’s QoL
Is it justified to give 2nd or 3rd line chemotherapy in a palliative setting?
Yes, if the disease remains chemo-sensitive e.g. breast cancer, ovarian cancer, colorectal cancer, and it is not damaging the patients QoL
Discuss when curative chemotherapy can occur
In some malignancies, there is a real chance of cure even if there is metastatic disease at presentation
This justifies the use of more intensive treatment associated with greater toxicity
Which cancers are suitable for curative chemotherapy?
Germ cell tumours, Hodgkin’s disease, Non-hodgkin’s lymphoma and many childhood cancers
Discuss some prophylactic treatments
Hormonal treatments may be given before overt malignancy appears - Tamoxifen for in-situ breast cancer before invasive carcinoma is recognised
Why are chemotherapies often given in combination?
- Different classes of drugs have different actions - kill more cancer cells together
- Less chance of drug-resistant malignant cells emerging
- drugs have different sites of toxicity, dose can be maintained for each drug
When is single agent Chemo appropriate?
Low performance status
Palliative setting
In which cancers are high dose, incredibly toxic, treatments justified?
Hodgkin’s disease
Ewings sarcoma
Is prolonged chemotherapy appropriate in remission?
Evidence suggests little advantage in most cancer, as resistant clones develop and toxicity increases
Used in childhood leukaemia, chemo is given for 18 months as maintenance following the induction of complete remission
Which cytotoxic drugs are available orally?
Cyclophosphamide, etoposide, capecitabine and tamoxifen
What are the advantages of oral chemo?
Patient does not have to have lengthy hospital visits and invasive procedures
When is intravesical chemotherapy used?
Superficial bladder cancer
Produces high doses at the site of the tumour with negligible systemic absorption - minimal systemic toxicity
When is intraperitonal chemotherapy used?
For tumours that have spread trans-coelomically e.g. ovarian cancer
When is intra-arterial chemotherapy used?
Any tumour that has a well-defined blood supply has the potential
e.g. hepatic artery infusion for liver metastases
Allows higher doses to be delivered to the involved site and reduces systemic toxicity
How are chemotherapy doses calculated?
They are calculated according to the patients Body Surface Area (BSA), using DuBois formula
Which chemotherapy drug has it’s dose calculated directly from renal function?
Carboplatin
In which cancers does chemotherapy have >50% cure rate, even in advanced disease?
Hodgkin’s disease, testicular cancer, acute lymphoblastic leukaemia, choriocarcinoma, paediatric cancers (including leukemia’s, lymphomas and sarcomas)
In which cancers does chemotherapy cure <50% of advanced disease?
Non-Hodgkin’s disease, ovarian cancer, paediatric neuroblastoma, adult osteosarcoma, Ewing’s sarcoma, and rhabdomyosarcomas
In which cancers does chemotherapy increase the cure rate in high risk local regional disease?
Breast, colorectal, non-small cell lung, esophageal and gastric cancer, bladder
In which cancers does chemotherapy prolong survival, but not really cure, in advanced disease?
Non small cell lung, colorectal, gastric, breast, bladder, prostate
In which cancers does chemotherapy palliate symptoms, but have a limited response?
Renal cancer, melanoma, head and neck cancer, pancreatic cancer, biliary-tract cancers
Which organ are platinums predominately toxic to?
Kidney
Which organ is paclitaxel predominately toxic to?
Bone marrow
What is the definition of ‘high-dose’ chemotherapy?
Chemotherapy agents at doses that require bone marrow support
What is bone marrow support?
May be achieved through bone-marrow transplantation, although peripheral haematopoiectic progenitors (stem cells) are now more commonly used
Needs to be in a specialist centre to avoid mortality
What is the mortality associated with high dose chemotherapy?
1-2%
What is a good treatment for chemotherapy induced N&V?
Ondansetron and other 5-HT antagonists
Discuss the myelosuppressive side effects of chemotherapy
Chemotherapy causes bone marrow suppression by killing haematopoietic progenitor cells. This leads to leucopenia and thrombocytopenia around 10-14 days after the beginning of a cycle
Neutrophil count of <0.5 = risk of infection
What is the nadir?
The point at which the patients WBCs and platelets are lowest after chemotherapy
How long does haematopoietic recovery take after chemotherapy?
3-4 weeks
Discuss the GI side effects associated with chemotherapy
Common
Oral mucositis
Diarrhoea
Constipation - usually due to decreased oral intake and dehydration from N&V
Sometimes a paralytic ileus can develop due to autonomic neuropathy after platinum agents or vinca alkaloids
What is a cold cap during chemotherapy aiming to prevent?
Alopecia
Which drugs are associated with peripheral neuropathies?
Platinum drugs - particularly cisplatin, taxanes and vinca alkaloids
Do peripheral neuropathies resolve?
May partially recover after a few months - but patients are often left with a residual deficit
Give examples of central neurological toxicity
Rare
Ifosfamide-induced encephalopathy
5-FU induced cerebellar toxicity
What drug is associated with ototoxicity?
Cisplatin
Cochlear damage rather than nerve damage is suspected
Get high tone hearing loss
Is the otoxicity associated with cisplatin permanent?
Yes
What auditory conditions exclude the use of cisplatin?
Pre-existing high-tone hearing damage
Which drug is associated with hemorrhagic cystitis and what is the treatment?
Cyclophosphamide and ifosfamide
Cause in a dose-dependent manner
Antidotes exist - Mensa - mops up extra
Give plentiful fluids and diuretics for forced diuresis and to clear drug out of bladder
Which drugs are particularly nephrotoxic?
Platinum agents, especially cisplatin + the alkylating agent ifosfamide
What drugs are associated with acute arrhythmia’s?
Doxorubicin and paclitaxel
Which drug is associated with coronary artery spasm, and thus cardiac ischaemia?
5-FU
Is full hepatic failure a common side effect of cytotoxic drugs?
No - a transient rise in liver enzymes may occur, but normally returns to normal. Very rare to get full liver failure
What is palmar plantar erythema (Hand-foot syndrome)?
Erythema of the palms of the hands and soles of the feet
Side effects do pass but patient will need to be given emolients and reviewed for other drug SE i.e. bowel toxicity in the case of 5-FU
What cytotoxic agents is palmar plantar erythema associated with?
5-FU, capecitabine and some targeted agents e.g. sunitibin, erlotinib
Which drug is associated with increased sun sensitivity?
5-FU
What does Bleomycin do to the skin?
Causes skin and nail pigmentation. It occurs in combination with pulmonary fibrosis and a common pathogenic process is thought to be responsible
Which drug is associated with myalgia and arthraliga, and what is the treatment?
Paclitaxel. NSAIDs
Which cytotoxic agents are associated with frequent hypersensitivity agents on administration
Paclitaxel and docetaxel
What are some of the long term complications of chemotherapy?
- Second malignancies - some cause sub-lethal DNA damage that can induce a secondary malignancy
- Fertility - alkylating can render people infertile, most drugs reduce fertility
- Pulmonary - fibrosis from drugs like bleomycin and busulphan.
- Cardiac - acute conduction deficits, long term cardiac fibrosis. Younger patients more susceptible
- Psychosocial - employment, relationships, insurance and social adaptation
Which are the most carcinogenic anti-cancer drugs?
Alkylating agents and procarbazine
Which drugs are most associated with long term pulmonary fibrosis or pneumonitis?
High-dose or prolonged administration of most alkylating agents i.e. bleomycin
What agent is associated with hypomagnesia?
Cisplatin
What is associated with cardiomyopathy?
Doxorubicin
