High-dose interleukin-2 (IL-2) and interferon were the most commonly administered therapies before the recent introduction of targeted agents, including vascular endothelial growth factor and mammalian target of rapamycin pathway inhibitors. Although the new agents result in a progression-free survival benefit, high-dose IL-2 remains the only agent with proven efficacy in producing durable complete and partial responses in patients with metastatic renal cell carcinoma (RCC). Furthermore, although the use of single-agent interferon has decreased significantly since the introduction of targeted therapy, it remains in the frontline setting in combination with bevacizumab as a result of 2 large phase III trials. Lastly, improved understanding of immune regulation has led to the advancement of targeted immunotherapy using immune checkpoint inhibitors that have shown promising activity and are moving forward in clinical development. This article focuses on the current status of immunotherapy in the management of metastatic RCC.
Saby George, Roberto Pili, Michael A. Carducci and Jenny J. Kim
Venkata Pokuri, Norbert Sule, Yousef Soofi, Bo Xu, Khurshid Guru and Saby George
Randomized trials support the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer based on a noted survival advantage, which appeared to be strongly related to downstaging of the cancer to pT0 (complete pathologic response). This report presents a case of an unusual mast cell response along with bladder wall thickening after neoadjuvant chemotherapy. However, the final cystectomy specimen did not reveal any residual tumor (pT0). The authors hypothesize that neoadjuvant chemotherapy could have caused the diffuse mast cell response, and that this profound inflammatory response can be used as a biomarker of complete response to chemotherapy.
Venkata K. Pokuri, Houman Nourkeyhani, Bodie Betsy, Laurie Herbst, Marcus Sikorski, Edward Spangenthal, Andrew Fabiano and Saby George
The testosterone surge and disease flare is a feared complication from initiation of gonadotropin-releasing hormone (GnRH) agonist treatment in advanced prostate adenocarcinoma. It is a common practice to start an average 7-day pretreatment regimen with an antiandrogen agent before initiating GnRH agonist therapy, to circumvent disease flare from testosterone surge. However, this might not be the best strategy and can be harmful, especially in patients at high risk of imminent organ damage from minimal testosterone surge. Surgical castration is a simple and cost-effective method that should be considered in these scenarios. But most patients refuse this procedure because of the permanent and psychologic impact of surgery. Novel GnRH antagonists, such as degarelix, and cytochrome P450 17 (CYP17) enzyme inhibitors, such as ketoconazole, achieve castrate-equivalent serum testosterone levels much faster than traditional GnRH agonists without the need for coadministration of antiandrogens. This article reports on 3 cases of impending oncologic emergencies in advanced prostate adenocarcinoma treated promptly with degarelix and ketoconazole without any disease flare related to testosterone surge. In the setting of symptomatic hormone-naïve metastatic prostate cancer, the authors suggest clinical trials using abiraterone, orteronel, and other newer agents that target the CYP17 axis (eg, ketoconazole) for fine-tuning the emergent medical castration methods and avoiding the dangers from the flare phenomenon.