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Renal cell metastatic sUNITinib

This protocol was published over 10 years ago and has been assessed by the reference committee as suitable to be reviewed as required. The review due date has been removed. If something in this protocol requires reference committee consideration, please click on the feedback button at the bottom of the page.

Read more about the as required review process in this factsheet.

Check for clinical trials in this patient group. Link to Australian Clinical Trials opens in a new tab or window website

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Cycle 1 and further cycles

Drug Dose Route Day
sUNITinib 50 mg ONCE a day * PO 1 to 28

*Sunitinib has not been studied in patients with poor performance status or in the elderly. Consider an alternative if available or start with 37.5mg daily.

*Reduce dose by 12.5 mg to a minimum of 25 mg if coadministered with a strong CYP3A4 inhibitor. Increase dose by increments of 12.5 mg to a maximum of 87.5 mg if coadministered with CYP3A4 inducer

Frequency:
42 days (sunitinib is taken daily for 4 weeks then 2 weeks break)
Cycles:
continuous until disease progression or unacceptable toxicity
Notes:

Consider an alternative dosing schedule of 50 mg daily for 2 weeks on and 1 week off every 21 days, if predicted or experienced intolerance to the standard 4 weeks on 2 weeks off schedule.rr

Drug status:

Sunitinib is PBS authority opens in a new tab or window

Sunitinib is available as 12.5mg, 25mg, 37.5mg and 50mg capsules

Cost:
~ $2,300 per month "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1 to 28
sUNITinib 50 mg (PO) ONCE a day for 4 weeks followed by a 2 week break

*Sunitinib has not been studied in patients with poor performance status or in the elderly. Consider an alternative if available or start with 37.5mg daily.

*Reduce dose by 12.5 mg to a minimum of 25 mg if coadministered with a strong CYP3A4 inhibitor. Increase dose by increments of 12.5 mg to a maximum of 87.5 mg if coadministered with CYP3A4 inducer

Frequency:
42 days (sunitinib is taken daily for 4 weeks then 2 weeks break)
Cycles:
continuous until disease progression or unacceptable toxicity

Cycle 1 and further cycles

Drug Dose Route Day
sUNITinib 50 mg ONCE a day * PO 1 to 28

*Sunitinib has not been studied in patients with poor performance status or in the elderly. Consider an alternative if available or start with 37.5mg daily.

*Reduce dose by 12.5 mg to a minimum of 25 mg if coadministered with a strong CYP3A4 inhibitor. Increase dose by increments of 12.5 mg to a maximum of 87.5 mg if coadministered with CYP3A4 inducer

Frequency:
42 days (sunitinib is taken daily for 4 weeks then 2 weeks break)
Cycles:
continuous until disease progression or unacceptable toxicity
Notes:

Consider an alternative dosing schedule of 50 mg daily for 2 weeks on and 1 week off every 21 days, if predicted or experienced intolerance to the standard 4 weeks on 2 weeks off schedule.rr

Drug status:

Sunitinib is PBS authority opens in a new tab or window

Sunitinib is available as 12.5mg, 25mg, 37.5mg and 50mg capsules

Cost:
~ $2,300 per month "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1 to 28
sUNITinib 50 mg (PO) ONCE a day for 4 weeks followed by a 2 week break

*Sunitinib has not been studied in patients with poor performance status or in the elderly. Consider an alternative if available or start with 37.5mg daily.

*Reduce dose by 12.5 mg to a minimum of 25 mg if coadministered with a strong CYP3A4 inhibitor. Increase dose by increments of 12.5 mg to a maximum of 87.5 mg if coadministered with CYP3A4 inducer

Frequency:
42 days (sunitinib is taken daily for 4 weeks then 2 weeks break)
Cycles:
continuous until disease progression or unacceptable toxicity
  • Advanced renal cell carcinoma (RCC) with clear cell histology
Caution with oral anti-cancer drugs

Select links for information on the safe prescribing, dispensing and administration of orally administered anti-cancer drugs. 

Read more about at COSA guidelines for the safe prescribing, dispensing and administration of systemic cancer therapy opens in a new tab or window and oral anti-cancer therapy opens in a new tab or window
Emetogenicity minimal or low

No routine prophylaxis required. If patients experience nausea and/or vomiting, consider using the low emetogenic risk regimen.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Cardiac toxicity

Tyrosine kinase inhibitors have been associated with cardiac complications of varying degrees and severity.

Patients, especially those with pre-existing cardiovascular disease, should have a baseline cardiac assessment including an electrocardiogram (ECG) and biochemistry and be closely monitored; consider an echocardiogram (ECHO) as clinically indicated.

Cardiac assessment should then be repeated as clinically indicated or when starting new medication which affects the QT interval.

Read more about cardiac toxicity associated with anti-cancer drugs
Prolongation of QT interval

This treatment may prolong the QT interval and increase the risk of cardiac arrhythmia. Use with caution in patients with a congenital long QT syndrome, patients treated with a high cumulative dose of anthracycline therapy, patients taking medications that may prolong the QT interval and those with electrolyte disturbances. Risk factors (e.g. electrolyte abnormalities) should be corrected, where possible, prior to commencement of treatment and the concurrent use of drugs that may prolong the QT interval should be avoided. Baseline and periodic monitoring of electrocardiogram (ECG) and electrolytes (potassium, magnesium, calcium) should be considered in patients at high risk of QT prolongation.

Read more about drugs that may prolong QTc interval at crediblemeds.org opens in a new tab or window (registration required).
Hypertension

Pre-existing hypertension should be adequately controlled prior to commencing treatment. Baseline blood pressure monitoring and repeated weekly for the first 6 weeks then regularly throughout treatment.

In severe or uncontrolled hypertension, treatment should be withheld until hypertension is controlled. Dose modification or permanent discontinuation may be necessary - refer to dose modification section for specific recommendations.
Hypothyroidism

Thyroid dysfunction in particular hypothyroidism may occur with this treatment. Monitor for signs and symptoms of thyroid dysfunction and manage as clinically appropriate.
Diarrhoea

Antidiarrhoeals (e.g. loperamide) are usually prescribed with this treatment.

Read more about treatment induced diarrhoea
Hand-foot syndrome

Hand-foot syndrome (palmar-plantar erythrodysaesthesia) and rash are common adverse effects with this treatment which generally appear during the first 6 weeks of therapy.

Read more about hand food syndrome or palmar plantar erythrodysaesthesia (PPE)
Dental review

Dental review prior to treatment then 6 monthly during treatment. Avoid dental procedures after commencing treatment to minimise risk of osteonecrosis of the jaw.

Read more about medication-related osteonecrosis of the jaw (MRONJ)
Wound healing

Some suggest (Bose et al. 2010- see link to abstract) that antiangiogenic tyrosine kinase inhibitors (TKI's) be interrupted for at least one week (48 hours for agents with short half life) before surgery and not re-initiated until adequate wound healing has occurred. At many institutions, therapy with these agents is held for four weeks after major surgery and for at least two weeks after minor surgery, although there are no prospective data validating this approach. The decision to resume therapy following a major surgical intervention should be based upon clinical judgement of recovery from surgery.

Read more about "Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care" opens in a new tab or window, Bose et al 2010r
Blood tests

FBC, EUC, eGFR and LFTs at baseline, repeat at week 2, then every 4 weeks. TFTs at baseline then repeat every 8 to 12 weeks.
Hepatitis B screening and prophylaxis

The requirement for routine screening for HBsAg and anti-HBc for patients receiving this treatment is unknown. Clinical judgement and individual patient situations should be taken into consideration.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease. Possible suboptimal response to inactivated vaccines.

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of fetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment 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. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact of cancer treatment on fertility opens in a new tab or window
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) opens in a new tab or window unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.
Haematological toxicity
ANC x 109/L (pre-treatment blood test)
1.0 to less than 1.5 Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well
0.5 to less than 1.0 Delay treatment until recovery
less than 0.5 Delay treatment until recovery and consider reducing sunitinib by 12.5 mg for subsequent cycles
Febrile neutropenia Delay treatment until recovery and consider reducing sunitinib by 12.5 mg for subsequent cycles
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 The general recommendation is to delay, however if the patient is clinically well it may be appropriate to continue treatment; refer to treating team and/or local institutional guidelines
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until recovery and consider reducing sunitinib by 12.5 mg for subsequent cycles
Kidney dosing recommendations 
eGFR (mL/min/1.73m2) Recommended dose
≥ 15 No dose modification necessary
Hepatic impairment
Use with caution as sunitinib has not been studied in patients with severe hepatic impairment
Hepatic metabolism / excretion is significant; consider dose modification for patients with mild to moderate impairment
Mucositis and stomatitis
Grade 3 Delay treatment until toxicity has resolved to Grade 2 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce sunitinib by 12.5 mg
2nd occurrence: Reduce sunitinib by a further 12.5 mg
3rd occurrence: Omit sunitinib
Grade 4 Omit sunitinib
Diarrhoea
Grade 3 Delay treatment until toxicity has resolved to Grade 2 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce sunitinib by 12.5 mg
2nd occurrence: Reduce sunitinib by a further 12.5 mg
3rd occurrence: Omit sunitinib
Grade 4 Omit sunitinib
Hand foot syndrome (link to  Hand foot syndrome (Palmar-plantar erythrodysaesthesia))
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce sunitinib by 12.5 mg
3rd occurrence: Reduce sunitinib by a further 12.5 mg
4th occurrence: Omit sunitinib
Grade 3 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce sunitinib by 12.5 mg
2nd occurrence: Reduce sunitinib by a further 12.5 mg
3rd occurrence: Omit sunitinib
Cardiac toxicity
Asymptomatic decline in LVEF *
(LVEF less than 50% or greater than 20% below baseline)		 Delay treatment until recovery and consider reducing sunitinib by 12.5 mg for subsequent cycles

(If no improvement in LVEF, cease sunitinib)
Symptomatic decline in LVEF Cease sunitinib

* Left Ventricular Ejection Fraction.

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources: 

For more information see References & Disclaimer.

Sunitinib
  Interaction Clinical management
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Increased toxicity of sunitinib and its active metabolite possible due to reduced clearance Avoid combination or monitor for sunitinib toxicity

If concomitant use of strong CYP3A4 inhibitors cannot be avoided, consider reducing sunitinib dose to a minimum of 37.5 mg daily for GIST and MRCC or 25 mg daily for pNET, based on careful monitoring of tolerability
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of sunitinib and its active metabolite possible due to increased clearance Avoid combination or monitor for decreased clinical response to sunitinib

If concomitant use of strong CYP3A4 inducers cannot be avoided, consider increasing sunitinib dose in 12.5 mg increments (up to 87.5 mg per day for GIST and MRCC or 62.5 mg per day for pNET), based on careful monitoring of tolerability
Drugs that may prolong the QTc interval (e.g. azole antifungals, tricyclic antidepressants, antiarrhythmics etc.) Additive effect with sunitinib; may lead to torsades de pointes and cardiac arrest Avoid combination or minimise additional risk factors (e.g. correct electrolyte imbalances) and monitor ECG for signs of cardiac arrhythmia
Drugs undergoing P-gp-mediated elimination (e.g. dabigatran, loperamide, phenytoin etc.) Increased effects/toxicity of these drugs possible due to inhibition of P-gp by sunitinib resulting in reduced clearance Avoid combination or monitor for increased effect/toxicity of interacting drugs
Bevacizumab Microangiopathic haemolytic anaemia Monitor for haemolytic anaemia, thrombocytopenia, hypertension, elevated creatinine and neurological symptoms
Levothyroxine  Reduced efficacy of thyroid replacement therapy resulting in hypothyroid symptoms; possibly due to induction of levothyroxine metabolism by sunitinib and subsequent TSH elevation Monitor closely for signs and symptoms of hypothyroidism, serum thyroxine and TSH levels; increase levothyroxine dose if needed
Temsirolimus Increased toxicity of sunitinib

Avoid combination or monitor for sunitinib toxicity
Antidiabetic agents  Hypoglycaemia Monitor blood glucose levels. Adjustment of the dose of antidiabetic medication may be required
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs) Additive nephrotoxicity Avoid combination or monitor kidney function closely
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inhibitors. If treating VTE, avoid use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window  inhibitors.

Dabigatran: avoid combination with strong P‑gp opens in a new tab or window inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update opens in a new tab or window

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Days 1 to 28

This is an oral treatment

Any toxicity grade 2 or greater may require dose reduction, delay or omission of treatment and review by medical officer before recommencing treatment.

Anti-cancer drug patient assessment tool prior to each treatment.

Sunitinib

  • administer orally ONCE a day
  • to be swallowed whole with a glass of water; do not break, crush or chew
  • may be taken with or without food

Note: missed doses should not be replaced; if a dose is forgotten or vomited, normal dosing should be resumed at the next scheduled dose.

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Discharge information

Sunitinib capsules - with written instructions on how to take them.

Antidiarrhoeals - as/if prescribed.

Patient information

Ensure patient receives protocol patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting

Early (onset days to weeks)
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following anti-cancer treatment, radiation therapy to the head, neck or oesophagus, and high-dose chemotherapy followed by a blood and marrow transplant (BMT).

Read more about oral mucositis and stomatitis
Diarrhoea

Read more about treatment induced diarrhoea
Fatigue

Read more about fatigue
Arthralgia and myalgia

Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation. 

Read more about arthralgia and myalgia
Palmar-plantar erythrodysaesthesia (PPE) - hand-foot syndrome (HFS)

Bilateral erythema, tenderness, pain, swelling, tingling, numbness, pruritus, dry rash, or moist desquamation and ulceration of the palms and soles. It is also known as hand-foot syndrome (HFS). Symptoms appear to be dose dependent and palms are affected more than soles.

Read more about hand-foot syndrome associated with chemotherapy
Skin and tissue discolouration

Discolouration of the skin or hair may be accompanied by other dermatological effects, including dryness, blisters and thickening or cracking of the skin.
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Hypertension

High blood pressure is commonly associated with many anti-cancer drugs. Pre-existing hypertension should be controlled prior to initiation of drugs capable of causing hypertension.
Haemorrhage
Cardiotoxicity

Cardiotoxicity may manifest as asymptomatic reduction in left ventricular ejection fraction (LVEF), arrhythmia, cardiomyopathy, hypertension, cardiac ischaemia and congestive heart failure (CHF). The risk of cardiotoxicity is increased by a number of factors, particularly a history of heart disease and electrolyte imbalances.

Read more about cardiotoxicity associated with anti-cancer drugs

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Alopecia - partial

Hair thinning and/or patchy hair loss. Patients can also experience mild to moderate discomfort of the hair follicles, and rarely pain as the hair is falling out.

Read more about alopecia and scalp cooling
Nail changes

Hyperpigmentation, paronychia, onycholysis, splinter haemorrhage, pyogenic granuloma formation, subungual haematoma and subungual hyperkeratosis are some of the nail changes associated with anti-cancer drugs.   

Read more about nail toxicities
Hypothyroidism
Osteonecrosis of the jaw (ONJ)

Exposed, necrotic bone in the maxillofacial region is associated with this treatment.  

Read more about medication-related osteonecrosis of the jaw

The evidence supporting the use of this treatment comes from a multicenter, randomised, phase III trial to receive either repeated 6-week cycles of sunitinib (at a dose of 50 mg orally once daily for 4 weeks, followed by 2 weeks without treatment) or interferon alpha (IFN) (at a dose of 9 million international units subcutaneously three times weekly).

750 patients were enrolled with previously untreated, metastatic renal-cell carcinoma between August 2004 and October 2005 at 101 centres with 375 patients in each group. The patients were greater 18 years of age, ECOG of 0 to 1, had clear cell histology and had received no prior systemic therapy for renal cell carcinoma, and were well balanced in respect to demographics and disease characteristics.r

The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, patient-reported outcomes and safety.

In addition, a randomised, double-blind, placebo-controlled, cross-over patient preference study (PISCES) was performed to investigate the influence of tolerability on continuing treatment with pazopanib or sunitinib amongst patients with metastatic RCC. It was found that 70% of patients preferred pazopanib, 22% sunitinib and 8% had no preference (p<.001). Patients cited less fatigue and better quality of life as the main reasons for preferring pazopanib.r (link to ID 820 Pazopanib protocol)

Results of the COMPARZ study demonstrated similar efficacy between pazopanib and sunitinib in the first line setting. Median PFS was 8.4 months for patients treated with pazopanib compared with 9.5 months for those treated with sunitinib (HR 1.047). Overall response rates were 31% for pazopanib and 25% for sunitinib. Pazopanib was associated with less fatigue than sunitinib (55% vs 63%), less hand-foot syndrome (29% vs 50%), less taste alteration (26% vs 36%) and less thrombocytopenia (41% vs 78%). Pazopanib was associated with more alanine aminotransferase elevation than sunitinib (60% vs 43%). Health related quality of life scores were better in the pazopanib treated group than those in the sunitinib treated group.r

Efficacy

The primary endpoint of the study comparing sunitinib and interferon was progression free survival, which was statistically better for sunitinib patients. Median progression-free survival was 11 months in the sunitinib group (95% CI, 10 to 12) and 5 months in the IFN group (95% CI, 4 to 6), and a hazard ratio of 0.42 (95% CI, 0.32 to 0.54; P<0.001).r

Kaplan-Meier Estimates of Progression-free Survival:r

© New England Journal of Medicine 2007

A final analysis in 2009 showed that the median overall survival was greater in the sunitinib group than in the IFN group (26.4 versus 21.8 months respectively; HR=0.821; p=0.051). Within the IFN group, 33% of patients received sunitinib, and 32% received other vascular endothelial growth factor inhibitors after discontinuation. Objective response rate was 47% for sunitinib compared to 12% for IFN (p<0.001).r

Health related quality of life was significantly better in the sunitinib group than in the IFN group (P<0.001), as reported by patients in post baseline assessments with the use of both FACT-G (Functional Assessment of Cancer Therapy-General) and FKSI (Functional Assessment of Cancer Therapy-Kidney Symptom Index) questionnaires.r

Kaplan-Meier Curves for Overall Survival:r

Median OS in the COMPARZ study was 28.3 months in the pazopanib group (95% CI, 26.0 to 35.5) and 29.1 months in the sunitinib group (95% CI, 25.4 to 33.1).

© N Engl J Med 2014

Toxicity

The median duration of treatment was 11 months in the sunitinib group and 4 months in the IFN group. Reasons for discontinuation were progressive disease (60% sunitinib; 65% IFN). Most treatment-related adverse events occurred more frequently in the sunitinib group than in the IFN group. A dose reduction occurred in 50% of patients in the sunitinib group and 27% of patients in the IFN group.r

Hypothyroidism has been associated with sunitinib treatment and was reported as any grade and grade 3 treatment-related adverse events in 14% and 2% of patients, respectively. Decline in left ventricular ejection fraction is a recognized adverse event associated with sunitinib. 13% of patients had a sunitinib treatment-related adverse event of ejection fraction decline as reported by investigators, including 3% with grade 3 severity which is comparable with that previously reported suggesting that this is not a cumulative effect with long-term sunitinib treatment.r

Toxicityr Sunitinib
n=375 (%)		 Interferon Alfa
n=360 (%)
All Grades Grade 3-4 All Grades Grade 3-4
Neutropenia 72 11 46 7
Anaemia 71 4 64 5
Diarrhoea 53 5 12 0
Fatigue 51 7 51 12
Nausea 44 3 33 1
Stomatitis 25 1 2 1
Hypertension 24 8 1 1
Hand and foot 20 5 1 0
Rash 19 2 6 1
Skin discolouration 16 0 0 0
Epistaxis 12 1 1 0
Headache 11 1 14 0
Increased creatinine 65 8 21 0

© New England Journal of Medicine 2007

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Version 7

Date Summary of changes
31/01/2024

Protocol assessed by eviQ medical oncology reference committee and deemed suitable to be reviewed as required. Flag added, review date removed and version number increased to V.7. Read more about as required review protocol status in this factsheet.

Version 6

Date Summary of changes
27/07/2023

Protocol updated with ADDIKD guideline recommendations. 

PDF of previous protocol.

Version number changed to V.6.

Version 5

Date Summary of changes
17/02/2010 Review, new dose modifications and transferred to eviQ.
21/07/2011 New format to allow for export of protocol information.
Protocol version number changed to V.2.
Additional Clinical Information, Key Prescribing table and Key Administration table combined into new section titled Clinical Considerations.
Drug specific information placed behind the drug name link.
12/01/2012 PHC view updated.
08/04/2013 Protocol reviewed by Medical Oncology Reference Committee.
Evidence updated to include data from the PISCES study.
Next review in 2 years.
09/05/2014 Protocol reviewed by Medical Oncology Reference Committee. Evidence updated, PHC view removed. Review 2 years.
31/03/2017 Protocol discussed and decided to have a 5 year review period. Next due for review in 2019.
31/05/2017

Transferred to new eviQ website. Protocol version number changed to V.3.

  • note added regarding an alternative dosing schedule of 2 weeks on and 1 week off as per reference committee consensus.
  • hepatitis screening changed to unknown.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.4.
25/03/2019 Protocol reviewed at Medical Oncology Reference Committee meeting on 15/03/2019. Patient information changed to non-chemotherapy version. Version increased to V.5. Next review in 5 years.
18/08/2020 Treatment schedule note relating to alternative dosing schedule reviewed electronically and updated by Medical Oncology Reference Committee. 
09/11/2021 Patient information title changed to "Kidney cancer advanced or metastatic".
21/12/2021 Changed antiemetic clinical information block to minimal or low, to align with new categories. See ID 7 Prevention of anti-cancer therapy induced nausea and vomiting (AINV) v5.
18/05/2022 Prolongation of QT interval clinical information block added.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/322

28 Apr 2025