CYTOTOXIC DRUGS - general Flashcards
The chemotherapy of cancer should be limited to specialists in oncology
- reconstituted by trained personnel
- reconstituted in designated pharmacy areas
- wear protective clothing
- use eye protection
- avoided by pregnant staff
- use local procedures for spillage, safe disposal, include syringes, containers and absorbent material
- monitor staff exposure to cytotoxins
What is “Neoadjuvant” and “Adjuvant” therapy?
“Neoadjuvant therapy”
- initial therapy that shrinks down the tumour
- This is so that later local therapy is more effective and less destructive (to the normal tissue)
- “Adjuvant therapy”
- surgery, chemotherapy, and radiotherapy that is given to prevent the cancer returning
Drug classes
alkylating agents
anthracyclines
antimetabolites
cytotoxic abx
platinum compounds
taxanes
vinca alkaloids
Alkylating Agents:
- Cyclophosphamide
- Ifosfamide
- Melphalan
- Bendamustine
Anthracyclines
- Daunorubicin
- Doxorubicin
- Epirubicin
- Idarubicin
Antimetabolites:
- Cytarabine
- Fluorouracil
- Methotrexate
- Mercaptopurine
Cytotoxic Antibiotics
- Bleomycin
- Mitomycin
- Platinum Compounds: Carboplatin Cisplatin Oxaliplatin.
Taxanes
- Cabazitaxel
- Docetaxel
- Paclitaxel
Vinca Alkaloids
- Vinblastine
- Vincristine
- Vindesine
Cytotoxin side effects
- Extravasation of Intravenous Drugs
- Oral Mucositis
- Tumor lysis syndrome
- Hyperuricaemia
- Bone marrow suppression
- Alopecia: common
- Thromboembolism
- Urothelial toxicity
- Myelosuppression
- N+V
Extravasation of Intravenous Drugs
Severe local tissue necrosis due to leakage of the cytotoxin
Oral Mucositis
- Very sore mouth
- More with Fluorouracil, Methotrexate and Anthracyclines (e.g. doxorubicin)
- Advise good oral hygiene, and sucking ice chips with fluorouracil
- Ice chips, antiseptic and anti-inflammatory mouthwash, ionic solutions and oral gels may help
- If caused by methotrexate: use folinic acid (levofolinic acid)
What drugs cause sore mouth as a side effect?
Fluorouracil, Methotrexate and Anthracyclines
Tumour Lysis Syndrome
- Occurs due to rapid destruction of malignant cells
- Higher risk in pre-existing hyperuricaemia, dehydration and renal impairment
- Causes HYPER K, Ph, Ca and uricaemia → renal damage and arrhythmias
Which cancers have higher risk of tumour lysis syndrome?
- non-Hodgkin’s lymphoma
- Burkitt’s lymphoma
- acute lymphoblastic leukaemia
- acute myeloid leukaemia
Hyperuricaemia
elevated serum uric acid level
Which cancers are hyperuricaemia more present in?
More present in high-grade Lymphoma and Leukaemia
Hyperuricaemia - treatment
- ALLopurinol started 24hrs before treating those tumours: hydrate patient
- Alterative: Febuxostat given 2 days before treatment
Bone-Marrow Suppression
- Caused by all drugs other than Vincristine and Bleomycin
- Occurs 7-10 days after administration
- Check blood count before treatments - reduce dose if bone marrow hasn’t recovered
- Avoid treatment during acute infection - or seek medical attention if currently taking
- Neutropenic fever Immediate → broad-spectrum antibiotics
Which drugs do NOT cause bone marrow suppression
Vincristine and Bleomycin
Alopecia
- Reversible hair loss is a common complication
- Varies between drugs and patients
- No pharmacological therapy is currently available to prevent this from happening
Urothelial Toxicity
- Causes haemorrhage in urinary tract
- Common in cyclophosphamide and ifosfamide
- Treated with Mesna
Myelosuppression
- Can be caused by methotrexate
- Use folinic acid to treat toxicity
Pregnancy and cytotoxic drugs
- Mostly teratogenic - not to be administered during pregnancy
- Exclude pregnancy before
- Advise on contraceptive before therapy begins
- Women of childbearing age to use contraception during and after treatment
Alkylating drug or procarbazine - effect on reproductive system
- Increased risk of permanent male sterility
- Consider sperm storage
- Affects women less - may cause onset of a premature menopause
Which drugs can cause increase risk of permanent male sterility
Alkylating drug or procarbazine
Symptoms of nausea and vomiting can be
acute
delayed
anticipatory
Delayed + anticipatory more difficult to control than acute
Nausea and vomiting - more common in
More common in women, patients <50, anxiety and repeated exposure
Mild risk of N+V
Mild: Fluorouracil, etoposide, methotrexate, vinca alkaloids
Moderate risk of N+V
- Taxanes
- doxorubicin
- Low cyclophosphamide doses
- mitoxantrone
- high methotrexate doses
High risk of N+V
- Cisplatin
- dacarbazine
- high cyclophosphamide doses
N+V - prevention of acute symptoms (within 24 hours of treatment)
Low risk patients: Dexamethasone or lorazepam
High risk patients: Ondansetron + dexamethasone + aprepitant
Prevention of delayed symptoms (after 24 hours of treatment)
Moderately emetogenic drugs: Dexamethasone + ondansetron
Highly emetogenic drugs: Dexamethasone + aprepitant
Prevention of anticipatory symptoms (occurs before treatment)
Lorazepam
Use of folinic acid
- They are used to counteract the folate-antagonist action of Methotrexate
- This speeds recovery from
Methotrexate-induced mucositis or myelosuppression
Alkylating agents - side effects
Cyclophosphamide Ifosfamide Melphalan
* Urothelial toxicity
* Increased risk of permanent male sterility
Anthracyclines - side effects
Daunorubicin Doxorubicin Epirubicin Idarubicin
* “Rubi-red urine”
* Formulations not interchangeable (conventional, liposomal, pegylated liposomal)
Cardiotoxic side-effects
Liposomal → reduced cardiotoxicity but causes painful macular skin eruptions
* Prevent skin eruptions by cooling hands / feet and by avoiding gloves / socks
Antimetabolites - side effects
Cytarabine Fluorouracil Methotrexate Mercaptopurine
* Mucositis and myelosuppression
AMENDMENTS
31/03/2024 - Tumour Lysis Syndrome should read:
Cytotoxic Antibiotics - side effects
Bleomycin Mitomycin
* Progressive pulmonary fibrosis
*Pulmonary toxicity
Taxanes - side effects
Cabazitaxel Docetaxel Paclitaxel
* Hypersensitivity reactions → premedicate with corticosteroids and antihistamines
* Monitor cardiac output
Monitor for signs and symptoms of pneumonitis and sepsis
Vinca Alkaloids - side effects
Vinblastine Vincristine Vindesine
* INTRAVENOUS ADMINISTRATION ONLY - INTRATHECAL = FATAL
*Bronchospasm
*Neurotoxicity - neuropathy, motor weakness, myalgia
