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DEFINITION OF “ELDERLY PATIENT” or for those with tumor progressing upon loco-regional
therapies. [10]
Due to the fact that aging involves a progressive shortening
[11]
of life expectancy and reduction in the functionality of organ The efficacy of sorafenib in HCC was established in SHARP
[12]
systems, the definition of an “elderly patient” is somewhat hazy and Asian-Pacific, two randomized, phase III multicenter,
[7]
and still a matter of debate. What is the upper limit of age double-blind, placebo-controlled trials that led to the
in which a patient is considered as old? Should the cut-off of approval of drug by the International Health Authorities.
70 years used in clinical studies and in current clinical practice In both studies, sorafenib administered at the dose of
to be considered an acceptable and reasonable boundary? Is age 400 mg twice daily demonstrated a statistically significant
the only parameter to take into account for defining an elderly improvement of overall survival and time to progression than
patient or should the so-called stage of aging be evaluated more compared to the placebo in patients with well-preserved
extensively? It has been demonstrated that the standardized liver function (Child-Pugh A). Sorafenib proved to be
geriatric evaluation systems, assessing additional parameters well-tolerated, with skin toxicity (hand-foot skin reaction),
such as comorbidities, cognitive, and health status, may better diarrhea, and asthenia representing the most common
correlate with therapy toxicity and patient outcomes, and could adverse effects. Temporary treatment interruptions and/or
[8]
subsequently supply additional information to the standard dose reductions along with immediate specific treatment
performance status scale, such as KPS or ECOG PS, normally used of adverse events proved effective in managing adverse
in oncology. However, there has yet to be a general consensus drug effects.
on what the best geriatric evaluation system to use is.
In the SHARP trial, the median age of patients treated with
sorafenib was 64.9 ± 11.2 years, whereas the Asia-Pacific
Due to their fragile conditions, elderly patients are generally
perceived to be more susceptible to the toxic effects of trial was 51 years (range 23-86). In both studies, the inclusion
cancer therapy and, as a result, gain less clinical benefits from criteria did not set an upper age limit. The Asia-Pacific study
treatments due to frequent dose interruptions or permanent included younger patients on account of the earlier onset
discontinuations of the drug. This perception could be of HCC in those regions. The preplanned subgroup analysis
related to the fact that this population is underrepresented according to the patients’ age grouping in the Asia-Pacific
study showed that sorafenib provided similar clinical benefits
in clinical trials, which are often conducted excluding patients in both younger (< 65 years) and older (≥ 65 years) patients.
exceeding a certain age limit or those bearing comorbidities.
Following the two registrative trials, the use of sorafenib
has also been evaluated in large patient populations treated
However, a growing body of evidence suggests that older according to everyday clinical practice.
patients with adequate organ function and a reasonable life
expectancy should receive the same treatment as younger Global Investigation of therapeutic DEcisions in HCC
patients. A retrospective analysis is evaluating 13 different and Of its treatment with sorafeNib, is an international,
molecularly targeted cancer therapies found similar frequencies post-approval, prospective, non-interventional study
of drug-related adverse events among the elderly as in younger undertaken to evaluate the safety and the efficacy of sorafenib
patients. To limit this gap and identify the most appropriate in patients with unresectable HCC, in which the inclusion
[9]
treatment of elderly patients, it is advisable to assess how criteria of patients closely corresponded to that of real-life
available treatment options behave in the framework of both practices. This study carried out in 39 countries worldwide,
[13]
well-conducted clinical trials and in everyday clinical practice. enrolled 3,371 patients; of these, 3,202 were available for the
evaluation of safety. Two interim analyses (after the accrual
TREATMENT WITH SORAFENIB of 500 and 1,500 patients, respectively) and the final analysis
confirmed the safety profile of sorafenib previously recorded
Therapeutic options for HCC range from surgeries (resection in the phase III pivotal trials, without detecting any new
or liver transplantation) to loco-regional therapies unexpected adverse events. A breakdown of the safety of
(percutaneous ethanol injection, radiofrequency ablation or sorafenib according to age groups was available only for the
trans-arterial chemo-embolization) and systemic treatment, second interim analysis (1,571 patients). The comparison
[13]
depending either on the stage of tumor disease or on the of sorafenib safety profiles in younger (< 65 years, n = 883)
underlying liver disease. Currently, treatment with sorafenib and older patients (≥ 65 years, n = 688) showed that the
has been recognized as the only standard systemic therapy incidence of adverse events, drug-related adverse events,
for HCC. It is indicated for patients with well-preserved liver and serious adverse events was independent of age, similar
function (Child-Pugh A class) and with advanced tumors in both older and younger patients. It is interesting to

Hepatoma Research | Volume 1 | Issue 2 | July 15, 2015 59