Optimal management of renal cell carcinoma in the elderly: a review

Figures & data

Table 1 Indications and contraindications of treatment options for small renal masses³¹

Treatment	Indications	Contraindications
Partial nephrectomy	Enhancing solid or complex cystic renal mass whenever technically feasible Fit patients with limited medical comorbidity Hilar tumors (contraindication to ablative treatment)	Severe and irreversible coagulopathy Abdominal scars (relative contraindication)
Ablative therapy	Renal masses < 3 cm Elderly patients or patients with medical comorbidities and high surgical risk who desire active treatment Patients with solitary kidneys and baseline renal dysfunction Informed younger patients who refuse surgery Renal masses in a postsurgical renal remnant	Healthy young patients Severe and irreversible coagulopathy Hilar tumors close to proximal ureter and central collecting system Tumors with irregular shape and infiltrative appearance Unwillingness to comply with a strict follow-up
Active surveillance	Patient with limited life expectancy Severe renal dysfunction	Unwillingness to comply with a strict follow-up

Table 2 Major drugs suspected of potential drug interaction with targeted agents

Cytochromes P450	Inhibitors	Inducers
CYP 1A2	Enoxacine, fluvoxamine	Alcohol, tobacco,
CYP 2C8	Gemfibrozil	St John’s wort
CYP 2D6	Fluoxetine, paroxetine, quinidine, thionidazine	(Hypericum perforatum),
CYP 3A4	Grapefruit juice, amiodarone, diltiazem, verapamil, ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, miconazole, ritonavir, nelfinavir, amprenavir, indinavir, atazanavir, erythromycine, Clarithromycine, josamycine, telithromycine	carbamazepine, phenobarbital, phenytoine, rifampycine, rifabutine, efavirenz, nevirapine, griseofulvine

Abbreviation: CYP, cytochrome P450.

Table 3 Algorithm for systemic treatment in metastatic renal cell carcinoma³⁰

Histology and setting	Risk group	Standard	Option
Clear cell first line	Good or intermediate Poor prognosis	Sunitinib, bevacizumab (±IFN), pazopanib Temsirolimus	Cytokines, sorafenib Sunitinib, sorafenib
Clear cell second line	Post cytokines	Sorafenib, pazopanib, axitinib	Sunitinib
	Post TKI	Everolimus, axitinib	Sorafenib
Clear cell third line	Post two TKIs	Everolimus
Non clear cell histology			Temsirolimus, sunitinib, sorafenib

Abbreviations: IFN, interferon; TKI, tyrosine kinase inhibitor.

Table 4 Summary of the phase III trials for approved agents with median age and oldest patient

Phase 3 trial	Median age (years)	Age of oldest patient (years)	Clinical benefita	PFS (months)	OS(months)	Toxicity
Sutent^Citation66	62	87	39.5%	11		Diarrhea, vomiting, hypertension, hand-foot syndrome, neutropenia, anemia, thrombocytopenia, cough, peripheral edema, fatigue, anorexia
Sorafenib^Citation67	58	86	57%	5.5	19.3	Diarrhea, fatigue, rash, hand-foot syndrome, anorexia, anemia, hypertension
Bevacizumab +	61	82	38.5%	10.2		Bleeding, hypertension, proteinuria
IFN-α^Citation9
Pazopanib^Citation10	59	85	68.3%	9.2		Diarrhea, vomiting, hypertension, hair color changes, nausea, anorexia, arterial thrombotic events, hemorrhagic events, ALT and AST elevation
Temsirolimus^Citation8	58	81	32.1%	3.8	10.9	Rash, peripheral edema, stomatitis, nausea, hyperglycemia, hyperlipidemia, hypercholesterolemia, diarrhea, anemia, dyspnea
Everolimus^Citation7	61	85	64%	4		Stomatitis, rash, fatigue, pneumonitis, diarrhea

Note:

a Clinical benefit = complete response + partial response + stable disease.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; IFN, interferon; OS, overall survival; PFS, progression-free survival.

Table 5 Specific considerations for the elderly at each stage of patient treatment

Patient selection	• Consider the following in the decision to start treatment:
	– Physiological age
	– Comorbidities
	– Drug toxicity profile
Before treatment	• Determine the patient’s goals for therapy
	• Advise the patient to resolve pre-existing health conditions, such as hypertension, skin disorders, and foot problems
	• Take a full inventory of the medications and dietary supplements the patient is taking
	• Inquire about the patient’s support system
	– Arrange regular nurse outreach, if necessary
	• Educate the patient on drug dosing and administration, and recognition and management of adverse effects
During treatment	Monitor for:
	• Emergence of adverse effects
	– Understand that some adverse effects may affect elderly patients differently than they would younger patients
	– Arrange regular nurse outreach, if necessary
	– Be prepared to act quickly and aggressively if adverse effects emerge
	– Consider dose modifications, if necessary
	• Quality of life
	– Regularly inquire about the impact of adverse effects on activity levels
	• Potential drug-drug interactions
	– Regularly inquire about any new medications the patient may be taking
	• Clinical response to treatment
	– Regularly perform imaging scans to monitor disease state

Adapted from Dutcher et al.⁶⁹

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