Reply to: “Sorafenib prolongs survival, but what happens to the symptoms?”
Authors: Tim Meyer, Uzma Asghar
Journal: Journal of Hepatology (2012)

Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?Journal of HepatologyVol. 56Issue 3PreviewHepatocellular cancer is a significant global health problem yet the prognosis for the majority of patients has not changed significantly over the past few decades. For patients with advanced disease, sorafenib is currently the standard of care providing a survival advantage of 2–3 months in selected patients. Cytotoxic chemotherapy has been used for over 30 years but definite evidence that it prolongs survival has been lacking. Resistance remains a significant barrier for both targeted and cytotoxic agents and an understanding of the underlying mechanisms is critical if outcomes are to be improved. Full-Text PDF Open AccessSorafenib prolongs survival, but what happens to the symptoms?Journal of HepatologyVol. 57Issue 1PreviewA recent review published in the Journal of Hepatology discusses the opportunities for chemotherapy in hepatocellular carcinoma (HCC) [1]. In this review, the authors conclude that “Sorafenib is currently regarded as the standard of care in selected patients with advanced HCC based on two large randomised placebo controlled trials” [2,3]. Furthermore, the introduction suggests its use as a palliative therapeutic. But what actually defines a palliative treatment? A decent definition of palliative chemotherapy is given by V.R. Full-Text PDF Open Access The main focus of our paper concerns the potential role of cytotoxic chemotherapy, which needs to be considered in the context of other standards of care [[1]Asghar U. Meyer T. Are there opportunities for chemotherapy in the treatment of hepatocellular cancer?.J Hepatol. 2012; 56: 686-695Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar]. As stated, the current standard of care for advanced HCC is sorafenib. An exhaustive review of the SHARP [[2]Llovet J.M. Ricci S. Mazzaferro V. et al.Sorafenib in advanced hepatocellular carcinoma.N Engl J Med. 2008; 359: 378-390Crossref PubMed Scopus (8542) Google Scholar] and AP [[3]Cheng A.L. Kang Y.K. Chen Z. et al.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.Lancet Oncol. 2009; 10: 25-34Abstract Full Text Full Text PDF PubMed Scopus (4226) Google Scholar] trial data was not within the scope of our review since these have been covered extensively in previous publications. We do, however, highlight both the survival benefit and the toxicity associated with sorafenib. Survival remains the primary end point for most phase III trials and is both robust and, as Dr. Strebel points out, relevant to patients. Similarly, the assessment of toxicity using National Cancer Institute’s Common Terminology Criteria is well validated. However, the assessment of time to symptomatic progression (TTSP) was done using change in performance status and the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index 8 (FHSI-8). The FHSI-8 is a tool developed to assess symptoms in hepatobiliary cancer patients in general and is not specific for HCC patients. It has been validated in only one small study of 51 patients of which only 10 had HCC [[4]Yount S. Cella D. Webster K. et al.Assessment of patient-reported clinical outcome in pancreatic and other hepatobiliary cancers: the FACT Hepatobiliary Symptom Index.J Pain Symptom Manage. 2002; 24: 32-44Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar]. Furthermore, the ability of the tool to detect clinically meaningful changes over time has not been determined. Although TTSP was a primary end point, the trial was not specifically powered to detect a difference in TTSP. Hence, the lack of difference between the control and treatment group may be due to the use of an insensitive tool, lack of statistical power or real. In discussing the option of sorafenib with patients, it is clearly important to fully inform them of the known benefits and the main toxicities. However, unless the patient has to pay personally, we do not agree that patients with advanced cancer should be advised of the cost of the treatment. Such information implies that the patient must judge whether their life is worth the cost. We believe the question of cost-effectiveness is one for the healthcare providers. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.