Venous access required
IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.
Hypersensitivity/infusion related reaction
High risk with carboplatin. Hypersensitivity risk increases with number of cycles of carboplatin. Rechallenge with carboplatin after hypersensitivity carries a high risk of anaphylaxis, and where clinically indicated, should be undertaken with a desensitisation protocol with appropriate supports in place. Refer to local institutional policy.
Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.
Even though a combination of an NK1 receptor antagonist, 5HT3, and a steroid is available on the on the PBS for the prevention of nausea and vomiting associated with all moderate to highly emetogenic anti-cancer therapies, we have opted not to include the NK1 in the treatment schedule.
Ensure that patients also have sufficient antiemetics for breakthrough emesis:
Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR
Prochlorperazine 10 mg PO every 6 hours when necessary.
Immune-related adverse events (irAEs)
Immune-related adverse events (irAEs) can occur early and escalate quickly in patients receiving immune checkpoint inhibitors. irAEs can also occur after discontinuation of treatment. Fatalities have been reported. Management of irAEs is largely based on expert opinion and consensus guidelines.
Examples of irAEs with high risk of mortality include:
- cardiac toxicity: myocarditis
- musculoskeletal toxicity: myositis
- neurological toxicity: encephalitis, Guillain-Barré syndrome, myelitis, myasthenia gravis
- pulmonary toxicity: pneumonitis
- skin toxicity: Stevens-Johnson syndrome, toxic epidermal necrolysis.
Examples of irAEs in order of frequency include:
- endocrinopathies: thyroid dysfunction
- gastrointestinal toxicity: diarrhoea
- musculoskeletal toxicity: arthralgia, myalgia
- skin toxicity: rash, erythema, pruritus
- Less common
- endocrinopathies: hypophysitis, type I diabetes mellitus
- gastrointestinal toxicity: colitis
- musculoskeletal toxicity: inflammatory arthritis
- ocular toxicity: dry eye
- renal toxicity
- skin toxicity: vitiligo
- endocrinopathies: primary adrenal insufficiency
- gastrointestinal toxicity: pancreatitis
- haematological toxicity
- musculoskeletal toxicity: vasculitis
- ocular toxicity: uveitis, iritis.
Proactive monitoring, patient self-monitoring and early reporting of adverse events is critical. Treatment interruptions/discontinuation, consultation with specialist and administration of corticosteroids and/or supportive care is required to minimise the risk of death.
Directly measured glomerular filtration rate (mGFR) is the preferred kidney function value in the Calvert formula, especially in patients with either:
- curative treatment intent
- clinical situations where estimated kidney function may be unreliable for accurate therapeutic dosing such as
- eGFR > 125mL/min/1.73 m2
- eGFR ≤ 45 mL/min/1.73 m2
- extremes of body size or muscle mass
In all other clinical situations, eGFR adjusted to an individual’s body surface area (BSA-adjusted eGFR) is a suitable alternative to directly mGFR for use in the Calvert formula.
Dyspnoea developing within hours of the infusion has been reported in about 10% of patients treated with gemcitabine.
Consider ECG and troponin at baseline. There is no clear evidence regarding the efficacy/value of baseline ECG or troponin in patients receiving immune checkpoint inhibitor therapy. Some cancer specialists obtain baseline testing, and others continue this through the initial period of therapy. Consider urinalysis at baseline, particularly in patients with additional risk factors for developing immune-related acute kidney injury.
FBC, EUC, eGFR, LFTs, calcium, magnesium, serum cortisol, TFTs and BSL at baseline.
Repeat FBC, EUC, eGFR, LFTs and BSL prior to each cycle and serum cortisol and TFTs alternate cycles. Repeat FBC, EUC, eGFR, LFTs prior to day 8 each cycle. Calcium and magnesium as clinically indicated. Check lipase and amylase if symptomatic of pancreatitis.
Recalculation of carboplatin doses at each cycle is unnecessary, except when baseline kidney function (e.g., eGFR) alters by greater than 20% or when there is a change in the clinical status of the patient.
In the absence of suspicion of immune related adverse events less frequent monitoring may be applicable, according to institutional guidelines. Evidence for the frequency of routine blood testing with immunotherapies varies within published studies and guidelines.
Hepatitis and HIV
Hepatitis screening is recommended in all patients who are to receive immune checkpoint inhibitors.
Immunotherapy is associated with inflammatory adverse reactions resulting from increased or excessive immune activity and patients are at risk of developing autoimmune hepatitis. It should be used with caution in patients who have a history of chronic hepatic infections (hepatitis B and C), detectable human immunodeficiency virus (HIV) viral load or acquired immune deficiency syndrome (AIDS).
Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.
The safety of having vaccinations during immunotherapy is unknown. Patients in the clinical trials were typically allowed to receive inactivated and recombinant vaccines but not live vaccines.
Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.
Read more about COVID-19 vaccines and cancer.
Effects of cancer treatment on fertility
Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment.
Studies to evaluate the effects of immune checkpoint inhibitor therapy on fertility have not been performed. Therefore, the effect on male and female fertility is unknown. Limited evidence supports that immune checkpoint inhibitor-related hypogonadism due to orchitis and hypophysitis can impact fertility. Immune checkpoint inhibitors can cause fetal harm when given to pregnant women. A pregnancy test should be considered in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. There is very limited evidence to provide guidance regarding contraception timelines. Some studies have demonstrated PD-1 receptor occupancy for greater than 9 months after anti-PD-1 therapy (Brahmer et al., 2010). As a result, some cancer specialists advise using contraception for at least six months or even as long as two years after treatment finishes.