Answer: The optimal first-line therapy for kidney cancer is still up for debate. What's described here is a relatively typical patient with kidney cancer, with what sounds like bone-only metastases. This presentation is relatively uncommon, but we certainly see it.
There is general consensus in the US that sunitinib,1-3 pazopanib,4 and bevacizumab/interferon5-7 are all reasonable front-line standards of care, based on the most robust clinical data and their side effect profiles (Table 1).8 We're waiting for a trial of sunitinib versus pazopanib that may inform that decision a little more, but, of course, there are not trials of every drug versus every other drug, so we really don't have definitive comparative data.
The issue of bone metastases is an interesting one. It seems that when patients with RCC fail their front-line therapy, they tend to do so preferentially in bone and brain. This observation comes from retrospective studies and isn’t definitive, but it suggests that the activity of these agents is perhaps less in those organ sites.
At this point, we do not have any bone-targeted therapy for patients with RCC. Radiation is most often used for alleviating pain and other problems caused by symptomatic bone metastases. The use of bisphosphonates in these patients has been explored, with mixed results.9-11 Unfortunately, the large trials of pamidronate, zoledronate, and now with denosumab haven't really included many kidney cancer patients; so, we don't know whether there really is an effect in these patients. My general practice is to use those drugs in patients with more extensive bone disease but not necessarily a single bone metastasis. But, that remains an unanswered question.
This patient has a number of options. If he is not eligible for a clinical trial—which he may not be because bone metastases are not measurable— then I think that sunitinib, pazopanib, or bevacizumab/interferon would be reasonable choices. We treat people with metastatic disease until they fail to respond or have toxicity. In someone with bone-only disease, that becomes difficult to judge. If all their disease is controlled and they have one new area that flares, is that really progression or not? That can be very hard to determine. The important thing is to not give up on any individual drug too soon. With our patients who have bone metastases and metastases to other organ sites, we will treat any worsening areas with radiation or other means but continue their systemic therapy.
Although there are many drugs available to treat RCC, the list is not unlimited. Our general practice is to drag our feet in changing therapy if we think there is still benefit with the existing drug. Many side effects, such as hypertension, mucositis, blood count problems, skin toxicity, and diarrhea can be managed without dose reduction. There are drugs to approach each of those toxicities; they are not always successful, but we can make the attempt. Once the severity reaches grade 3 or higher, though, dose reduction may be necessary. Fatigue and hand-foot syndrome do require dose reduction when they get severe enough. We really don't have great ways to manage them.