Week 6 - cancer drugs/chemotherapy

Dacarbazine - class

Alkylating agents

Dacarbazine - indications

• melanoma

• soft tissue sarcomas

• hodgkins lymphoma

dacarbazine - moa

Exerts cytotoxic effects via action as alkylating agent

• potentially inhibits DNA synthesis

Dacarbazine - side effects

• anaemia

• decreased appetite

• nausea, vomiting

• thrombocytopenia

• leucopenia

Cyclophosphamide - class

Alkylating agent

Cyclophosphamide - indications

• Rheumatoid arthritis

• malignant disease

Cyclophosphamide - moa

• Prevention of DNA synthesis - fragmentation of DNA

• DNA damage via formation of cross links

Cyclophosphamide - side effects

• Alopecia

• Anaemia

• fever

• haemorrhage

• thrombocytopenia

• increased risk of infection

Rituximab - class

Monoclonal antibodies (anti-lymphocytes)

Rituximab - indications

• Rheumatoid arthritis

• Non-hodgkins lymphoma

• pemphigus vulgaris

Rituximab - moa

Cause lysis of B lymphocytes

• Targets CD20 (involved in cell cycle regulation and apoptosis) = promotes cell lysis

Rituximab - contraindications

Severe infection

Rituximab - SE

Doxorubicin - class

Anthracyclines and related drugs

Doxorubicin - indications

• Acute leukemias’s

• hodgkins & non-hodgkins lymphoma

• Solid tumours

• soft tissue sarcoma

• bladder cancer

• ovarian cancer

• breast cancer

• multiple myeloma

Doxorubicin - moa

• Intercalated into DNA = destabilising nucleosome structures leading to eviction and replacement of nucleosome

• disrupt topoisomerase-mediated repairs and free radicals-mediated cellular damages

Doxorubicin - SE

Crazy amount:

• alopecia, skin reaction/ ulcers, muscle weakness

• chills, insomnia, malaise, cough, dry mouth

• diarrhoea, nausea, vomiting, constipation

Tretinoin - class

Retinoid & related drugs

Tretinoin - indications

Acute promyelocytic leukaemia

Tretinoin - moa

Binding to and activating two types of nuclear receptors - retinoic acid receptors (RARs) alpha, beta, and gamma and retinoid X receptors (RXRs).

• Induces terminal differentiation in haemopoietic precursor cell lines and ALP cells

Tretinoin - SE

• Alopecia, skin reactions

• Diarrhoea, nausea, vomiting, dry mouth

• Anxiety, chills, confusion, depression

Paclitaxal - class

Taxanes

Paclitaxal - indications

• ovarian cancer

• Non-small cell lung cancer

• breast cancer

• AIDS-related Kaposi’s sarcoma

Paclitaxel - moa

Interferes with normal microtubule growth - destroying cells ability to use its cytoskeleton in a flexible manner.

• specifically binding to beta subunit of tubulin

Paclitaxel - contraindications

Acute porphyrias

Paclitaxel - SE

So many!

• Alopecia, skin reactions

• Diarrhoea, nausea, vomiting, constipation, GI discomfort

• Vertigo, dizziness, chills, insomnia

Tamoxifen - class

Anti-oestrogens

Tamoxifen - indications

• Oestrogen receptor positive breast cancer

• Breast cancer

• Anovulatory infertility

Tamoxifen - MOA

Competitively inhibits oestrogen binding to its receptor

• leads to a decrease in tumour growth factor α and insulin-like growth factor 1, and an increase in sex hormone binding globulin

• Overall reduces levels of factors that stimulate tumour growth

Tamoxifen - Contraindications

Personal or family history of idiopathic venous thromboembolism

Tamoxifen - SE

• Alopecia, anaemia

• Embolism and thrombosis

• Fatigue, nausea, vomiting

5-fluorouracil - class

Antimetabolite

5-fluorouracil - indications

• solid tumours

• colorectal cancer

• superficial malignant skin lesions

5-fluorouracil - moa

Analogue of the pyrimidine uracil, is a cytostatic that inhibits DNA and RNA synthesis, resulting in growth inhibition of malignant and pre-malignant cells.

5-fluorouracil - contraindications

• history of heart disease

5-fluorouracil -SE

Alopecia; diarrhoea; increased risk of infection; mucositis; nausea; skin reactions; vomiting

Etoposide - class

Topoisomerase II inhibitor

Etoposide - indications

• Testicular cancer,

• Small cell lung cancer,

• Hodgkin's lymphoma,

• Non-Hodgkin's lymphoma,

• Acute myeloid leukaemia,

• Ovarian cancer