Chemotherapy in metastatic renal cell carcinoma today? A systematic review

Abstract

The prognosis of patients affected by metastatic renal cell carcinoma (mRCC) has improved markedly with targeted therapies. Unfortunately, 20-25% of the patients are refractory to treatment at the first response assessment and most patients will acquire drug resistance during the treatment. Moreover, current data on the clinical activity of targeted agents in poor risk or non-clear-cell mRCC patients are inconclusive because of the absence of prospective trials. Therefore, there are still several patients in need of new therapeutic approaches to improve clinical outcomes. Kidney cancer is historically considered resistant to chemotherapy on the basis that the results of phase II trials have not always been promising. We carried out a systematic review of both monochemotherapy and polychemotherapy alone or combined with immunotherapy or targeted agents in mRCC to define the state of the art and to evaluate further clinical research fields. All retrospectives, phase I/dose finding, phase II and phase III studies on chemotherapy in mRCC, published in the literature from January 2003 to November 2012, with at least 20 patients enrolled, were evaluated. Although the results of clinical trials have often been disappointing, in selected cases of mRCC, chemotherapy may have a promising antitumor activity, particularly when there are sarcomatoid differentiation features, or in highly progressive disease where the combination of doxorubicine plus gemcitabine or capecitabine has yielded interesting results. Chemotherapy may play a role in mRCC, whereas targeted agents and immunotherapy have not yielded durable and satisfactory results; further studies are needed.

Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase

“…Such malignancies as melanoma, glioblastoma, non-small lung cell and advanced renal cancers, among others, have been generally refractory to standard chemotherapies with cytotoxic agents due to their high levels of intrinsic resistance to apoptosis and/or the development of the multidrug resistance (MDR) phenotype [1–3]. The prognosis is somewhat better with the recently approved therapies based on targeted agents.…”

Chronic Oxidative Stress Increases Resistance to Doxorubicin-Induced Cytotoxicity in Renal Carcinoma Cells Potentially Through Epigenetic Mechanism

“…The mechanism of chemotherapeutic resistance in kidney cancer is not fully understood. It is in this context that the novel findings of this study suggest that chronic oxidative stress can lead to increased resistance to doxorubicin, a chemotherapeutic drug widely used for treatment of various cancers and currently under clinical trial for combination therapy in kidney cancer (Roubaud et al, 2011;Haas et al, 2012;Buti et al, 2013). Additionally, the data of this study also suggest that oxidative stress-induced resistance to doxorubicin in kidney cancer cells is, at least in part, mediated by epigenetic inactivation of MMR-dependent apoptotic pathway.…”

Dose-finding/phase II trial: bevacizumab, immunotherapy, and chemotherapy (BIC) in metastatic renal cell cancer (mRCC). Antitumor effects and variations of circulating T regulatory cells (Treg)

“…We also underline that in many phase III studies recently published, among the list of the treatment received after or before PR partial response, CR complete response SD stable disease, PD progressive disease, DCR disease control rate (response rate+stable disease rate), NV not evaluable, TTP time to progression, OS overall survival Table 4 Efficacy results in naïve and pretreated patients c Overall survival in pretreated and naïve patients the agents of the protocols, the chemotherapy was often mentioned. [26][27][28][29].…”