Comparing comparators: a look at control arms in kidney cancer studies over the years.

In the past decade, an increasing number of frequently positive randomised clinical trials have been completed, allowing new consideration of the present therapeutic armamentarium for advanced renal cell carcinoma. These studies were predominantly designed to compare the experimental drugs with 1 of 2 active control arms: interferon alpha-2a or sorafenib. Different from expectations, the final results of some of these studies were not in line with the predictions, and the reasons have not been fully investigated. Consequently, there is a great need for careful analysis of the studies carried out so far, chiefly the role and validity of the control arms. In this regard, the examination of patient baseline characteristics and other factors of potential interest seems fundamental for a correct analysis of the results of these trials and consequent optimal use of the available targeted agents.

Sunitinib re-challenge in advanced renal-cell carcinoma.

Despite offering significant clinical benefits in advanced renal-cell carcinoma (RCC), the effectiveness of targeted therapies eventually declines with the development of resistance. Defining optimal sequences of therapy is therefore the focus of much current research. There is also evidence that treatment 're-challenge' may be an effective strategy in some patients. We review evidence to evaluate whether sunitinib may have value as re-challenge therapy in patients who have progressed on prior targeted therapy with sunitinib and/or an alternative tyrosine kinase inhibitor or mammalian target of rapamycin inhibitor. Re-challenge with sunitinib appears to be of clinical benefit, thus representing a feasible therapeutic option for patients with advanced RCC who are refractory to other treatments and are able to receive further therapy. These observations support hypotheses that resistance to targeted agents is transient and can be at least partially reversed by re-introduction of the same agent after a treatment break. Median progression-free survival durations appear to be shorter and response rates lower on re-challenge than following initial treatment, although a wider interval between treatments appears to increase response to sunitinib re-challenge.

Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma.

BACKGROUND: A large amount of evidence suggests a possible role of interleukin-6 (IL-6) in the pathogenesis of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We studied both IL-6 and A(1)FP in patients with HCC, non-neoplastic liver disease or in healthy controls. RESULTS: IL-6 titers were four-fold higher in cancer than in cirrhotic patients and 25-fold higher than in healthy controls. As for alpha1-fetoprotein (A(1)FP) titers, the highest levels were observed in cancer patients. Receiver operating characteristic (ROC) curves analysis demonstrated that IL-6 is significantly more discriminant than A(1)FP, with 'optimal' cut-off values of 7.9 pg/ml (sensitivity = 0.83, specificity = 0.83, efficiency = 0.83). The ROC curves used to distinguish HCC from cirrhotic patients only, showed higher discriminant power of IL-6 versus A(1)FP titers, with a new cut-off value of 12 pg/ml (sensitivity = 0.73, specificity = 0.87, efficiency = 0.8). Discriminant analysis on HCC and non-HCC subjects yielded sensitivity, specificity and efficiency rates of 77%, 93% and 88%, respectively. The overall efficiency of the two tests combined was 82%. CONCLUSIONS: IL-6 could be considered a promising tumor marker for HCC. In particular, the diagnostic value of the test is significantly increased when combined with A(1)FP.

Uncovering Pandora's vase: the growing problem of new toxicities from novel anticancer agents. The case of sorafenib and sunitinib.

As newer, molecularly targeted, anticancer drugs are entering clinical practice, a wide array of previously unrecognised and ill defined side effects of these drugs are increasingly observed. Sorafenib and sunitinib are two of these novel agents, acting on tumour angiogenesis as well as on other key proliferative pathways; recently approved for the treatment of advanced kidney cancer, they may cause peculiar cutaneous, vascular and mucosal toxicities, including hand-foot skin reaction, skin rash, hypertension and GERD-like oesophagitis/gastritis. In this review, we shall deal with these poorly recognised, but sometimes extremely distressing, toxicities; pathophysiologic mechanisms will be discussed and suggestions for treatment of each toxicity will be proposed, based on the few pieces of evidence available and, especially, on our empirical experience.