To date, even if sorafenib currently represents the best therapeutic option for patients with advanced hepatocellular carcinoma (HCC), the published data concerning the tolerability and impact on quality of life of this drug in elderly patients is quite limited. That appears unjustified if we consider that the incidence of HCC significantly increases with advancing age, reaching a peak at ∼75 years; furthermore, given that the incidence of HCC is increasing worldwide, the proportion of elderly patients with HCC is expected to steadily rise in the next years; finally, the efficacy of a cancer treatment in the elderly patient should be primarily assessed in terms of improvement of quality of life and maintenance of an adequate self-sufficiency and only secondarily in terms of prolonging survival.
Therefore, we conducted a retrospective analysis to evaluate the tolerability of sorafenib in elderly patients with advanced HCC. The study involved a consecutive cohort of 31 patients, aged between 70 and 83 years, with advanced HCC, Child-Pugh A or B, Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2, and who were not suitable candidates for or had progressed after locoregional therapies. Patients were treated with single-agent sorafenib, at a standard dose of 400 mg twice daily orally. Treatment was continued until disease progression or unacceptable toxicity. Self-sufficiency and impact of treatment on quality of life were assessed administering the IADL (Instrumental Activities of Daily Living) scale at baseline and every clinic visit. Adverse events (AEs) were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0.
Our sample included an elderly population with frequent comorbidities. The most represented (80.6%) were cardiovascular diseases (primarily hypertension). Therefore, blood pressure was monitored weekly during the first 6 weeks of treatment and regularly thereafter. No adjustment or new institution of antihypertensive therapy was required. The median duration of sorafenib treatment was 139 days, ranging from a minimum of 1 to a maximum of 12 months. AEs were reported in all patients, mostly during the first month and of grade 1 or 2. Grade 3 side effects were fatigue (22.6%), hand-foot syndrome (19.3%), thrombocytopenia (12.9%), hyperbilirubinemia (9.7%), abdominal pain (9.7%), and, only in one case, diarrhea (3.2%). No grade 4 toxicity was noted (Table 1). At baseline, the IADL score was >5 in 22 (71%) patients. Only 150 days after starting treatment, that IADL score decreased in 6 (19.3%) of 21 patients. This proves that the observed toxicity did not affect the quality of life and the level of self-sufficiency of most patients.
|Toxicity||Grade 1||Grade 2||Grade 3||Total|
|HFS||6 (19.3%)||3 (9.7%)||6 (19.3%)||15 (48.4%)|
|Diarrhea||7 (22.6%)||6 (19.3%)||1 (3.2%)||14 (45.2%)|
|Abdominal pain||7 (22.6%)||1 (3.2%)||3 (9.7%)||11 (35.5%)|
|Fatigue||7 (22.6%)||10 (32.2%)||7 (22.6%)||24 (77.4%)|
|Anorexia||0 (0%)||9 (29.0%)||0 (0%)||9 (29.0%)|
|Nausea||4 (12.9%)||1 (3.2%)||0 (0%)||5 (16.1%)|
|Hyperbilirubinemia||9 (29.0%)||3 (9.7%)||3 (9.7%)||15 (48.4%)|
|Hypertransaminasemia||18 (58.1%)||6 (19.3%)||0 (0%)||24 (77.4%)|
|Thrombocytopenia||13 (41.9%)||3 (9.7%)||4 (12.9%)||20 (64.5%)|
|Neutropenia||1 (3.2%)||4 (12.9%)||0 (0%)||5 (16.1%)|
|Anemia||1 (3.2%)||3 (9.7%)||0 (0%)||4 (12.9%)|
Our results indicate that sorafenib therapy is well tolerated also in elderly patients with advanced HCC and it has a positive impact on their self-sufficiency and quality of life.
Given the retrospective nature and the small sample size of this analysis, our conclusions could be considered not generalizable. However, we hope that they will prompt future prospective studies which will focus more on the HCC elderly population.
Edoardo Francini, M.D.Vincenzo Bianco, M.D.
Sapienza University of Rome Medical Oncology Unit Rome, Italy