Week 2 - H - Cyctotoxic chemotherapy - Cell cycle specific/non-specific durgs, side effects & stem cell transplantation Flashcards
The most common treatment for people with leukaemia / lymphoma is chemotherapy Clinical remission may be where the glands risen at the start of the disease may have gone away after treatment but on scanning, may well see the disease is still present What is used to identify radiological remission in a patient with Hodgkins disease?
Would use a PET scan to identify remission
Cytotoxic drugs can be classified as Cell cycle specific or Non cell cycle specific Are cell cycle specific more tumour specific or not? Does it focus more on dose or duration of the treatment?
Cell cycle specific drugs are generally more tumour specific and there is more importance on duration of treatment rather than dose
The two main types of cell cycle specific cytotoxic drugs are the antimetabolite and mitotic spindle inhibitors Where in the cell cycle do each of these drugs work?
The anitmetabolite agents impair nucleotide synthesis by affecting the S phase The mitotic spindle inhibitors affect the M phase of the cell cycle - the mitotic phase
Antimetabolites affect synthesis of the DNA which happens in the S phase of the cell cylce What is hydroxyurea also known as? What condition causing anaemia is it sometimes used in if severe?
Hydroxyurea is also known as hydroxycarbaamide Hydroxyurea is given in sickle cell anaemia if there is frequent sickle cell crises - it stimulates the production of HbF (in acute crisis, oxygen, hydration - IV fluids, opiates and they may require exchange transfusion if severe)
Non cell cycle specific agents are the other type of cytotoxic drugs Are these tumour specific? Is the dose more important than duration here?
Cell cycle specific drugs These are generally tumour specific The duration of the treatment is more important than the dose Non-cell cycle specific drugs These are not tumour specific and therefore damage nomral stem cells Also the cumulative dose is more important than duration
What are the usual immediate effects of cytotoxic drugs? What are the cell cycle specific drugs? (duration important) What are the non-cell cycle specific drugs? (dose important)
Usually will get hair loss - alopecia, bone marrow suppression, gut mucosal damage - nausea & vomiting Bone marrow suppression reduces neutrophil count Cell cycle specific drugs Anti-metabolite drugs - inhibit DNA synthesis is S phase Mitotic spindle inhibitors - inhibit mitosis in M phase Non cell cycle specific Alkylating agents, platinum derivatives, cytotoxic antibiotics
The long term side effects of the drugs are group/drug specific One of the anthracyclines is used in the treatment of NHL, which is this?
Hydroxydanuorubicin
When considering using combination chemotherapy, what are the three things to consider?
Ensue there is non-cross resistant drug combinations No overlapping toxicity otherwise these side effects will be very likely and synergistic effect of adding the drugs together
Why does chemotherapy fail?
It fails if there is slow doubling time for the tumour Tumour sanction formation - some cancers can evade the chemo And tumour mutations eg p53 mutation One of the paradoxes of treating lymphomas is aggressive lymphomas although more aggressive may be cured but non-aggressive cannot be cured due to the slow doubling time – chemo only works if the tumours are dividing
Most chemo mechanisms use the normal p53 programmed cell death to effect a response If – p53 mutation then the chemo will not work Hence why the more targeted drugs are used if there is mutations What is a syndrome where p53 mutation predisposed to cancer development?
Li–Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder that pre-disposes carriers to cancer development due to a germline mutation in the p53 tumour suppressor gene
This syndrome is also known as the sarcoma, breast, leukaemia and adrenal gland(SBLA) syndrome. The mutations can be inherited, or can arise from mutations early in embryogenesis, or in one of the parent’s germ cells. Certain pathogens can also affect the p53 gene. What is the pathogen in hman papilloma virus which results in inactivation of the p53 gene? What else does HPV inhibit to prevent cell cycle death?
HPV encodes a protein, E6, which binds to the p53 protein and inactivates it. This mechanism, in synergy with the inactivation of the cell cycle regulator pRb by the HPV protein E7, allows for repeated cell division manifested clinically as warts. p53 and pRB are tumour suppresor genes
What are the cons of intensify chemotherapy when treating a disease?
It can lead to severe marrow myelosuppression
What can the myelosuppression cause by chemotherapy be overcome by?
Can be overcome by giving growth factors - granulocyte colony stimulating factors (GCSF) or By intensifying the dose of drugs and giving stem cells to the patient
Source of Stem Cells for Transplantation Patient source * Autologous * Allogeneic * sibling * unrelated Tissue source Blood versus bone marrow What is the difference between allogenic and autologous stem cells?
Autologous stem cell transplants are predicated on a simple concept: if a little chemotherapy has the potential to cure, than a lot could be even better. Allogeneic stem cell transplants are predicated on the idea that if your immune system could not detect and destroy your lymphoma before it became obvious, then maybe an immune system from someone else (a sibling or an unrelated but ‘matched’ person), can identify your lymphoma as ‘foreign’, and mount an immune response against it.
What are the pros and cons of autologous vs allogenic?
Autologous haemopoietic stem cell transplant * Pros - no chance of rejection, no need for donors, available for most patients * Cons - may need 100% gene modification and likely require combo therapies Allogenic * Pros - complete replacement of host cells and may not require genetic modification * Cons - need for matched donors and greater chance of morbidity due to GVHD/immunosuppresion
