Cytotoxic Drugs

Who should manage chemotherapy treatment?

Treatment of cancer with chemotherapy is limited to oncology specialists

How can chemotherapy drugs harm healthcare workers?

Chemotherapy drugs can harm workers through:

• Skin contact

• Inhalation

• Ingestion

Potential harmful effects include:

• Nausea

• Organ damage

• Skin reactions

• Reproductive effects

Why should women of childbearing potential avoid handling chemotherapy drugs?

• Risk of birth defects (teratogenicity)

• Risk of foetal loss/miscarriage

What precautions should be taken when handling chemotherapy drugs?

• Employers must provide adequate staff training

• Handle drugs in enclosed systems with ventilation

• Wear PPE and eye protection

• Practice good hand hygiene

• Ensure safe waste disposal

• Follow proper spillage handling procedures

What are examples of alkylating agents?

• Cyclophosphamide

• Ifosfamide

• Melphalan

What are examples of platinum compounds?

• Carboplatin

• Cisplatin

• Oxaliplatin

What are examples of antimetabolites?

• Cytarabine

• Fluorouracil (5-FU)

• Methotrexate

• Mercaptopurine

What are examples of anthracyclines?

• Daunorubicin

• Doxorubicin

• Epirubicin

• Idarubicin

What are examples of cytotoxic antibiotics?

• Bleomycin

• Mitomycin

What are examples of taxanes?

• Cabazitaxel

• Docetaxel

• Paclitaxel

What are examples of vinca alkaloids?

• Vinblastine

• Vincristine

• Vindesine

What are examples of aromatase inhibitors?

• Anastrozole

• Exemestane

• Letrozole

How can breast cancer be treated systemically?

• Chemotherapy

• Endocrine (hormonal) therapy

What is neoadjuvant therapy used for?

• Given before primary treatment (e.g. surgery)

• Used to reduce tumour size

Which breast cancers are treated with endocrine therapy neoadjuvant?

• ER-positive (oestrogen receptor-positive) cancers

• Works by targeting oestrogen pathways

What endocrine therapy is used in postmenopausal women with medium-to-high recurrence risk?

• Aromatase inhibitor first-line:

  • Letrozole

  • Anastrozole

• May switch to tamoxifen

What endocrine therapy is used in postmenopausal women with low recurrence risk?

Tamoxifen

What endocrine therapy is typically used in premenopausal women and men?

• Tamoxifen first-line

• May later switch to an aromatase inhibitor

How long is endocrine therapy usually given for?

• Standard duration: 5 years

• Extended therapy may continue up to 10 years

• Tamoxifen commonly used for extended therapy

Most common adverse effects of letrozole, tamoxifen, anastrozole (breast cancer) bicalutamide, goserelin (prostate cancer)?

symptoms of oestrogen depletion → e.g. vaginal dryness, hot flushes, loss of bone density

Tamoxifen → VTE

Tamoxifen interactions

CYP inhibitor → CYP2C9) responsible for metabolising warfarin

SSRIs → inhibit hepatic activation of tamoxifen.

What are the risk factors for breast cancer?

• Age, early onset of menstruation, late menopause, older age at first completed pregnancy, and a family history of breast cancer

• HRT and hormonal contraception

• obesity and alcohol consumption

What factors are protective against breast cancer?

Physical activity and breast-feeding

Define non invasive cancer?

ductal carcinoma insitu where cancer remains localised in ducts

What is most cancer when diagnose?

Invasive breast cancer, where malignant cells spread beyond the ducts,

early breast cancer (stage I/II),

locally advanced disease (stage III)

advanced disease (stage IV).

What is the main treatment for Early and locally advanced breast cancer?

Operable breast cancer → surgery

Often followed by adjuvant drug therapy to eradicate the micro metastases that cause relapses

Invasive

• Radiotherapy is recommended after surgery

What may be adjuvant therapy in Early and locally advanced breast cancer?

chemotherapy, endocrine therapy, biological therapy, or bisphosphonate therapy.

What chemo is used on adjuvant therapy for Early and locally advanced breast cancer?

Adjuvant anthracycline–taxane combination

What Biological therapy is used on adjuvant therapy for Early and locally advanced breast cancer?

Trastuzumab should be offered to patients with tumour size T1c and above HER2-positive invasive breast cancer

What Endocrine therapy is used on adjuvant therapy for Early and locally advanced breast cancer?

Tamoxifen → men and premenopausal women with oestrogen receptor positive invasive breast cancer

Post menopausal women with oestrogen receptor positive invasive breast cancer → aromatase inhibitor

What Bisphosphonate therapy is used on adjuvant therapy for Early and locally advanced breast cancer?

Zoledronic acid and clodronate disodium → disease free survival in post menopausal with node-positive invasive breast cancer

What neoadjuvant therapy can be given in Early and locally advanced breast cancer?

Chemo → reduce tumour size in patient with oestrogen-receptor-negative invasive breast cancer

Chemo + Endocrine → HER2 positive trastuzumab and pertuzumab

Endocrine

What is the recommended first line treatment in oestrogen receptor positive advanced breast cancer?

endocrine therapy

Aromatase inhibitors should be offered to postmenopausal women

Ovarian function suppression should be offered to pre and peri-menopausal women

Tamoxifen should be offered as first line treatment to men with oestrogen receptor positive advanced breast cancer

When should chemo be offered in advanced breast cancer?

first line treatment in patients with oestrogen-receptor-positive advanced breast cancer that is imminently life-threatening or requires early relief of symptoms

When should Bisphosphonate be offered in advanced breast cancer?

Patients with metastatic breast cancer to reduce pain and prevent skeletal complications of bone metastases.

What should be given in Familial Breast cancer?

Chemoprevention should be offered to all women who have been identified as being at high-risk of developing breast cancer

5 years

Tamoxifen → premenopausal

Anastrozole → postmenopausal women who do not have severe osteoporosis

What is prostate cancer treatment usually guided by?

baseline prostate specific antigen (PSA) levels, tumour grade, the stage of the tumour, the patients life expectancy, treatment morbidity and patient preference

What are treatment options in prostate cancer?

watchful waiting, active surveillance, prostatectomy, radiotherapy (such as external beam), brachytherapy, hormone therapy, and chemotherapy.

Difference between watchful waiting and active surveillance

Watchful waiting controlling rather than curing prostate cancer

Active surveillance, a 'curative' strategy, is aimed at patients who do not wish to have immediate treatment

What does hormone therapy in prostate cancer include?

includes anti-androgen → to block the affects of androgens

androgen deprivation therapy such as a luteinising hormone-releasing hormone (LHRH) agonist

bilateral orchidectomy

Treatment for low-risk localised prostate cancer

offer a choice between active surveillance, radical prostatectomy or radiotherapy

Treatment for Intermediate risk localised prostate cancer

radical treatments (prostatectomy or radiotherapy) should be offered, and for those who decline them, active surveillance can be considered

Treatment for high-risk localised prostate cancer

• when there is a realistic prospect of long-term disease control),

  • and in those with locally advanced disease, radical prostatectomy or radiotherapy should be offered.

Treatment for intermediate‐risk and high-risk localised prostate cancer who have chosen radical radiotherapy

• Offered in combination with androgen deprivation therapy

• Androgen deprivation therapy should be given for 6 months before, during or after radiotherapy;

• in patients with high‐risk localised prostate cancer, consider continuing therapy for up to 3 years

What chemo may be used in prostate cancer?

docetaxel [unlicensed indication]

Patients with newly diagnosed metastatic prostate cancer who do not have significant comorbiditie

What are the risks and benefits of combination treatment with chemo

frequently more toxic than single drugs

Certain tumours → enhanced response, reduced development of drug resistance and increased survival.