Classical chemotherapies Flashcards
What are some examples of first generation anthracyclines?
Doxorubicin
Daunorubicin
What is daunorubicin also known as?
Cerubidine
Daunomycin
Rubidomycin
What are some examples of second generation anthracyclines?
Epirubicin
Idarubicin
What are some of the disadvantages of the anthracyclines?
They are orally inactive and therefore have to be administered by intravenous injection
Have a lot of cardiotoxic side effects
Multi-drug resistance can develop due to amplification of the gene coding for the P-glycoprotein resulting in increased drug efflux from the cell (pumped out).
How do anthracyclines cause cardiac failure?
Have a lot of cardiotoxic side effects due to the generation of free radicals through the mitrochondrial redox cycling of the anthracyclines in the cardiomyocyte which results in cardiac decline and eventually dilated cardiomyopathy
When is doxorubicin indicated?
Treatment of solid tumours
Leukaemias
Lymphomas
Childhood tumours
When is daunorubicin indicated?
Acute leukemia
(acute myeloid leukemia and acute lymphoblastic leukemia)
What is epirubicin effective aganist?
Breast cancer
Is the first or second generation anthracyclines considered to be more cardio- toxic?
First generation, idarubicin (a second generation anthracycline has the additional benefit of being able to be taken orally).
When is idarubicin indicated?
Haematological malignancies
When is mitoxantrone indicated?
Advanced breast cancer
Certain lymphomas and leukemias
Which anthracyclines can be given to treat acute leukemias?
Dactinomycin (acute myeloid)
Doxorubicin (non-specific acute)
Daunorubicin (non-specific acute)
Mitoxantrone (non-specific leukemia)
Amsacrine (acute myeloid leukemias)
What is bleomycin indicated for?
Skin cancer
Testicular carcinomas
Lymphomas
When is dactinomycin indicated?
Solid tumors such as:
Wilm’s tumor (kidney tumor often occuring in childhood)
Ewing’s tumor
What are the main examples of non-intercalating agents used in the treatment of cancer?
Etoposide
Teniposide
Topotectan
Irinotectan
What are the main indications of etoposide and teniposide?
Small cell lung cancer and testicular cancer
What are the main indications of Topotectan?
Advanced ovarian cancer when other treatments have failed
What is a major side effect of Irinotectan?
Severe diarrhea
What is Irinotectan usually administered with in the combination therapy for advanced colorectal cancer?
Fluorouracil
Folinic acid (leucovorin)
What is the difference in mechanism between vinacristine and paclitaxel?
Vinacristine is a vinca alkaloid whereas paclitaxel is a taxane. Vinca alkaloids work by inhibiting polymerisation by binding to tubulin which halts the cell cycle as the chromosomes are unable to be separated in the anaphase.
Taxanes instead work by inhibiting depolymerisation which works by preventing the cell from dividing in telophase.
How does erublin work?
Inhibits depolymerisation and triggers apotosis of the cells.
When would you expect to see erublin licensed?
Recurrent and inoperable breast cancers
What are the most commonly used taxanes clinically?
Paclitaxel
Erublin
Carbazitaxel
Which type of taxane is often used in combination with prednisolone?
Carbazitaxel for hormone refractory prostate cancer
What are the similarities in indication between paclitaxel and docetaxel?
Both used for breast cancer
Paclitaxel is also used for ovarian cancer and both are used for other types of cancer
What are some of the main resistance mechanisms for paclitaxel and docetaxel?
Tubulin mutations resulting in weaker binding interactions
Over-expression of the p-glycoprotein resulting in faster efflux from the cell
Can taxanes be taken orally?
No, paclitaxel has a very poor solubility in addition
When do the taxanes usually act in the cell cycle?
G2/M checkpoint
When are the vinca alkaloids usually indicated?
Solid tumors (breast and lung)
Lymphomas
Leukemias
What are the main vinca alkaloids used in drug therapy?
Vinacristine
Vinablastine
Vindesine
What is the main side effect associated with vinca alkaloids especially with vinacristine?
Peripheral neurotoxicity
What are the three hormone therapies used in the treatment of estrogen-receptor positive breast cancer in post-menopausal women?
Anastrazole
Letrozole
Exemestane
What are three hormone therapies used in the treatment of hormone dependent breast cancer?
Tamoxifen
Tormifine
Fulvestrant
What are some of the indications of methotrexate?
Acute lymphoblastic leukemia
Non-hodgkins lymphoma
Solid tumours
What are some of the mechanisms of resistance that occurs with methotrexate?
Enhanced expression of dihydrofolate reductase
Diminished uptake by the reduced folate carrier (the responsible protein carrier that transports the drug into the cell)
When is 5-fluorouracil usually indicated?
Solid tumors such as breast cancer and in the gastro-intestinal tract cancers
Used alongside folinic acid (leucovorin) to treat colorectal cancer/
Why is it beneficial to use 5-fluorouracil topically?
Used for the treatment of skin cancer as it has a high selectivity for cancer cells over normal cells.
How can resistance to 5-fluorouracil occur?
When the cell produces high levels of dUMP to compete with the cell for the active site.
What is a common side effect of methotrexate, 5- flurouracil and Mercaptopurine?
Myelosuppression
What may you prescribe alongside methotrexate, 5- flurouracil and Mercaptopurine?
Due to the side effect of myelosuppression may prescribe filagrastim s/c injection to boost neutrophil production.
What is capecitabine metabolised to?
5-flurouracil
When is capecitabine indicated?
Alternative to flurouracil in the treatment of colorectal cancer alongside folinic acid
Metastatic bone cancer
Advanced gastric cancer
Advanced colon cancer
What is a unique side effect of antimetabolites?
Elimination of finger prints due to inflammation
When is uridine triacetate usually given?
Treatment of an overdose of capecitabine or flurouracil
What is the indication of chlormethine?
Hodgkins lymphoma
What are the indications of melphalan used?
Multiple myelomas
Advanced breast and ovarian
Which drugs are used to treat chronic lymphatic and lymphocytic leukemia respectively?
Bendamustine and uracil mustard are used to treat lymphatic leukemia whereas chlorambucil is used to treat chronic lymphocytic leukemia.
What is the indication of estramustine?
Treatment of prostate cancer
In addition to leukemia what are the other indications for Bendamustine and Chlorambucil?
Lymphomas and Hodgkins disease respectively
How does resistance to alkylating agents occur?
Reaction with cellular thiols and decreased cellular uptake
What are the indications of cyclophosphamide?
Leukemia, lymphomas, soft tissue sarcoma, solid tumors
What is a side effect of cyclophosphamide?
Haemorrhagic cystitis resulting in inflammation, bleeding, ulceration, oedema and cell death caused by the metabolite acrelin.
How can haemorrhagic cystitis be prevented?
Co-administration of mesna or increasing fluid intake
What is the indication of busulfan?
Treatment of chronic myeloid leukemia, increases life expectancy by a year
Can busulfan damage the bone marrow?
Yes but only when used excessively
What are some of the indications of cisplatin?
Head and neck cancer
Lung
Cervical
Bladder
Testicular
Ovarian
Which anti-emetic is used to overcome side effects of cisplatin?
Ondasteron (5HT3 receptor antagonist)
When is carboplatin preferred over cisplatin?
Advanced ovarain tumours or to treat lung cancer
Has reduced side effects compared to cisplatin
What are the main long term side effects of cisplatin and carboplatin?
Acoustic nerve damage and nephrotoxicity
Which drug has a better safety profile in comparison to cisplatin and carboplatin?
Oxaliplatin (used to treat colorectal cancer)
What are the three ways resistance to cisplatin and other related drugs can occur?
Increased drug efflux out of the cell
If there are low concentrations of the transporter protein required for cisplatin to enter the cell
High concentrations of thiols which can react with the activated species from cisplatin.
