Drug specific side effects of chemotherapy

Question 1

Platinums

Answer 1

• Very emetogenic
• Ototoxic
• Nephrotoxic

Question 2

Platinums - management

Answer 2

• IV fluids before and after administration.
• Urine output > 100 ml/hour
• GFR tests
• Audiology tests
• Strong anti-emetics, e.g. NK-1 inhibitor such as aprepitant.

Question 3

Aprepitant

Answer 3

• Only licensed to be used in conjunction with dexamethasone and a 5-HT3 antagonist.
• Dexamethasone doses reduced due to synergistic effect.

Question 4

Methotrexate

Answer 4

• Nephrotoxic
• Mucositis

Question 5

Methotrexate - management (nephrotoxicity)

Answer 5

• Urine output must be >100 mL/hour.
• Bicarbonate
• Acetazolamide

Question 6

Bicarbonate + Acetazolamide

Answer 6

• Promote excretion
• Increase urine pH from 6-7
• Methotrexate and its metabolites are poorly soluble at acidic pH.
• Increase in urine pH = increased solubility (by 5-8 fold).
• Reduces intratubular crystal formation (precipitation)

Question 7

Methotrexate - management (mucositis)

Answer 7

• Mouthwash
• Analgesia
• Folinic acid

Question 8

5-fluorouracil (5-FU/CAPECITABINE)

Answer 8

• Anti-metabolites
• Capecitabine = pro-drug of 5FU
• Inhibit pyrimidine synthesis
• Diarrhoea
• Palmar-Plantar Erythema (PPE) with capecitabine

Question 9

5-fluorouracil (5-FU/CAPECITABINE) - monitoring

Answer 9

• Dihydropyrimidine dehydrogenase (DPD) deficiency testing

Question 10

(5-FU/CAPECITABINE) - managament (PPE)

Answer 10

Pyridoxine

Question 11

Vinca alkaloids

Answer 11

• Inhibit spindle formation
• Little myelosuppression
• Neurotoxic+++
• Constipation often an issue

Question 12

Nitrogen mustards

Answer 12

• Cyclophosphamide and isosfamide.
• Forced diuresis and hydration
• Both – haemmorrhagic cystitis.
  
  • Mesna
• Ifosfamide – encephalopathy.
  
  • Methylene blue
• Confusion, drowsiness.

Question 13

Docetaxel

Answer 13

• Neutropenia
• Can progress to neutropenic sepsis, defined as:
  
  • neutrophil count </=0.5 × 109/L
    and:
  • a temperature higher than 38oC or
  • other signs or symptoms consistent with clinically significant sepsis, e.g. hypotension

Question 14

Docetaxel - management

Answer 14

• GCSF prophylaxis (growth factor)

Question 15

ANTHRACYCLINES

Answer 15

• Doxorubicin, epirubicin, idarubicin, daunorubicin and mitoxantrone.
• Type 1 cardiotoxicity - results from cumulative administered dose and is irreversible
• Lifetime cumulative dose:
  
  • Doxorubicin – 450mg/m2
  • Epirubicin – 900mg/m2
• Central lines reduce cardiotoxicity

Question 16

Trastuzumab

Answer 16

• Selectively targets HER2
• HER2 present in myocardium - cardiotoxic.
• Type 2 cardiotoxicity - reversible.