Update from the Spanish Oncology Genitourinary Group on the treatment of advanced renal cell carcinoma: focus on special populations

Abstract

Elderly or frail patients are often excluded from clinical trials. As a result, clinical outcome of these patients may differ from those obtained in trials. This situation may also hold true for patients who have severe concomitant diseases such as renal, hepatic, or cardiac dysfunction. Being aware of the wide range of clinical situations that a specialist may face is important to ensure that under any circumstances, the patient will receive the best treatment possible. The Spanish Oncology Genitourinary Group issued its first public statement on recommendations for the optimal management of advanced renal cell carcinoma (RCC). However, some issues remained unsolved. In this report, we discuss the current role of Medical Oncology in the treatment of patients with advanced RCC and review the management of special patient populations, such as elderly or patients with concomitant diseases.

Changing Mechanisms of Action as a Strategy for Sequential Targeted Therapy of Metastatic Renal-Cell Carcinoma

“…It is supposed to be the result of activation of feedback loops that promote the activation of molecular signaling pathways of survival, increased activity of mTOR-complex 2, up-regulation of insulin-like growth factor and increase in the ERK/MAPK pathway signaling [4,24,25].…”

“…Zhang concluded that reversible changes in gene expression within the tumor cells and/or their microenvironment could be the possible mechanism of reversible resistance. He implanted sorafenib-resistant RCC into mice and after implantation tumors regained the sensitivity to sorafenib [4,25].…”

“…Several factors play important role in selection of second line strategy: clinical evidence, toxicity issues and individual patient profile [4,25,26].…”

“…Despite this, the evidence of this approach is not strong; prospective, phase III trials are missing. Changing mechanism of action can have several advantages: greater chance of overcoming resistance while decreasing the probability of cumulative toxicity [4,25]. Toxicities of TKI-s and mTOR inhibitors for example, differ considerably.…”

“…Patients on targeted therapies progress some time during their treatment and mRCC is considered an incurable disease [4]. In trying to overcome this, the mechanism of action and especially mechanisms of resistance to targeted therapies, need to be studied and explained even more in detail [3][4][5][6][7].…”