BERKELEY, CA (UroToday.com) - The best practice for mRCC patients who failed first-line targeted therapy (such as sunitinib or sorafenib) has been to transition to everolimus, axitinib or other tyrosine kinase inhibitors. However, an escalated dosage of sorafenib has proved to have reversible toxicity and tolerable adverse effects and may be another choice instead of changing a drug after progression. In the current study we investigated the role of subsequent dose-escalation of sorafenib on the outcome of selected mRCC patients and also to find out the clinical-pathological characteristics that could predict favorable outcome for these patients. As a result, we observed long PFS and OS in those dose-escalated patients and confirmed some favorable predictive factors for better disease control (pre-escalation Karnofsky performance status, serum calcium concentration, PFS, etc.). We also found new factors, apart from traditional MSKCC scores, such as neutrophil-lymphocyte ratio and highest toxicity grade at the routine dosage. This reminded us that immune responses are inevitable parts in tumor treatments (paying more attention to the rising star PD-L1). On the other hand, adverse events might be a good parameter for us to determine the best tolerable/effective doses.
It needs to be mentioned that the favorable outcome may have been due to the specific inclusion criterion in our trial that only patients who didn't progress during 3 months of the initial sorafenib treatment period were eligible for inclusion. They were further screened as follows: 1) a 3 months’ observation time informed us that they were safe with the treatment. 2) they had either slowly growing metastasis sites or that they had good response to sorafenib. As long as they progressed, the most simple and cost-effective treatment method was dose escalation instead of changing to another TKI since we knew upfront that the escalation would be safe and effective.
There is still much to do in investigating the best treatment strategies such as dose-escalating or TKI rechallenge in the treatment of mRCC. In all, we believe in the next decades individualize target therapy strategies to extend its benefits is of great interest.
Ding-wei Ye 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.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China, and
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China