Treating patients with metastatic renal carcinoma: An escape from Phase III, "Beyond the Abstract," by Fable Zustovich, MD, et al

BERKELEY, CA (UroToday.com) - The wide availability of drugs for the treatment of advanced renal cell carcinoma (RCC) has recently provided many alternatives for patients historically treated with only interferon or interleukin. These new currently used drugs became available to physicians after the approval processes performed by regulatory agencies, based mainly on the results of Phase III studies. Unfortunately, due to the stringent entry criteria of clinical studies, patients are not representative of the entire population; results of Phase III studies are extrapolated to all RCC populations without taking into account patients with different comorbidities. In fact, the current clinical practice management includes situations such as metabolic disorders, advanced age, liver disorders, infections and brain metastasis, which are frequently observed, but not always included in phase III trials.

With these assumptions, besides phase III trials, expanded-access programs, phase II studies, subgroup and retrospective analyses, and direct experience in clinical practice should also be considered to avoid critical situations related to unexpected toxicity. In this regard, the example of cardio-toxicities, which have negatively affected the tolerability of sunitinib, is emblematic.

Therefore, we suggest a departure from phase III trials. The choice of the most suitable drug should be made in relation to the degree of the patient’s frailty and/or with reference to specific comorbid situations. Moreover, it is universally recognized that there is no single treatment suitable for all patients. Keeping in mind these issues, the purpose of this review is to analyze and weigh the safety data available for the drugs approved for RCC. Moreover, we suggest the best therapy, in terms of both efficacy and safety, be based on the multiplicity of features of each patient in relation to the main characteristics of each agent. Consequently, we decided to match the whole bulk of data coming from literature with the experience acquired in our institution.

To put these theoretical assumptions into practice, we believe that because comorbidity is an independent cause of mortality for cancer patients, and may be associated with a reduced tolerance to anticancer agents, the first step is an unbiased evaluation of the level of the patient’s frailty, chiefly for those age 65 years and older. In this step, it must also be evaluated whether the cancer is likely to decrease the patient’s life expectancy. The subsequent step should consist of evaluating all coexisting medical conditions such as hypertension, cardiovascular or heart-related conditions, respiratory diseases, diabetes, metabolic disorders, and immune system decline. It is our opinion that, in absence of head-to-head study, the choice of the most suitable drug should be made in relation to the degree of the patient’s frailty and/or with reference to specific comorbid situations.

Our main conclusions were as follow:

  • Sunitinib is unsuitable for elderly patients or patients with cardio-toxicity or with liver toxicity
  • Everolimus is unsuitable for patients with metabolic toxicities, infection
  • Pazopanib is unsuitable for patients with liver toxicity or cardiotoxicity

Finally, the statement made by Christopher Ryan at the American Society of Clinical Oncology 2010 annual meeting is worth mentioning and will continue to be relevant in the future: “all targeted agents are valid, provided they are used correctly.”

 

Written by:
Fable Zustovich, Giuseppe Lombardi, and Patrizia Farina as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

IRCCS Istituto Oncologico Veneto
Medical Oncology
Via Gattamelata, 64
35128 Padua, Italy

Treating patients with metastatic renal carcinoma: An escape from Phase III - Abstract

More Information about Beyond the Abstract