BERKELEY, CA (UroToday.com) - Even though it’s uncertain whether we can extrapolate the experience of one single case to generalized application, in rare case scenarios like the present one, the value of a case report might shed some light for those who will come across a similar situation in the future. The criticism of this report may include that ‘as a single case no causal relationship can be proven, or further, as a single experience the efficacy cannot be ascertained.’
Current medicine places much emphasis on evidence-based medicine and results of well-designed, large-scale randomized, comparative clinical trials. The conclusions of these level 1 or 2 trials, of course, can be applied to common patients, and yet the patients we encounter daily may still deviate in varying degrees from the ideal index patients who meet all the inclusion criteria of the studies -- not to mention in rare cases where no clinical trials could be performed because the limited case numbers throughout the world.
There is much high-quality evidence in guiding treatment of patients with metastatic renal cell carcinoma (mRCC). But treatment for such a patient with concomitant mRCC and a functioning allograft has rarely been reported. That caused a major concern from the beginning, because the new anti-cancer therapy would be constructed on top of the original complex management of transplant immunosuppression, and, of course, the patient wanted to maintain his graft kidney function if at all possible. Among the choices were cytokine (interleukin-II) therapy, target therapy using tyrosine kinase inhibitors which focus more on the inhibition of vascular endothelial growth factor (VEGF) pathway (sunitinib, sorafenib, pazopanib, axinitib, etc.), and mammalian target of rapamycin inhibitor (mTORi, temsirolimus, everolimus). We started him on temsirolimus therapy—for which we considered his combined mRCC and transplant as a poor risk factor; we were more familiar with mTORi because of the experience of using sirolimus as a transplant immunosuppressant. At the time of starting his temsirolimus therapy, everolimus had not been approved by the FDA for treating mRCC, otherwise it would likely have been our preferred choice.
Yes, we should refrain from generalizing based on our observation, but the treatment is still in line with the current treatment guideline for mRCC. We carefully adjusted his immunosuppression by frequent monitoring of the therapeutic drug levels and other laboratory and clinical follow-up to discontinue his original cyclosporine and mycophenolate therapy, while leaving him on low-dose steroids. Obviously there is much more to be explored to understand the mechanisms behind different dosing strategies among mRCC patients and transplant recipients, even with the same mTORi. And one more question that lies ahead is what would be our next step strategy when this patient starts to demonstrate progression with temsirolimus therapy.
By Shih-Chieh Jeff Chueh, MD, PhD 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.
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH USA