Older patients benefit from lower doses of sunitinib in renal cell carcinoma
Dr Ravindran Kanesvaran - National Cancer Centre Singapore, Singapore
A few years ago… I’m actually based in Singapore, outside of the National Cancer Centre in Singapore, and I had this opportunity to do a fellowship in geriatric oncology at Duke University, North Carolina in the United States under the mentorship or tutelage of Professor Harvey Cohen who is one of the pioneers in SIOG and world renowned in this area of geriatric oncology. So during that year I was attached to him in the geriatric department and also to the oncology department. He came up with a structured programme which basically constituted a fellowship in geriatric oncology.
The key messages would be how to come up with a programme that integrates the principles of geriatric patients with key principles in oncologic treatment and mash both together in a manner where we can apply some of these key principles in a day-to-day practice in dealing with treating older cancer patients. I spent a lot of time on how to assess older cancer patients in the geriatric unit; at the same time, my other fellowship was in urological cancers where I got to see a lot of older patients because I treat prostate cancer. I got to use principles on geriatric assessment on these older prostate cancer patients and it helped me to tease out who was fit for treatment and how to offer patients treatment in spite of them being older in age; how to dispel this concept of ageism which a lot of us have a bias against – when we see a patient we look at their age rather than their constitutional state or performance status. So a lot of these principles that I learned from the geriatric clinics I applied.
What did the study entail?
Basically we did not specifically design this for older cancer patients. We enrolled patients in a retrospective manner, or at least we analysed data in a retrospective manner, looking at Asian or Singaporean patients who used sunitinib as part of their treatment for metastatic renal cell carcinoma in the first line. Initially when the drug was first approved we realised that a lot of these patients had a lot of toxicity and, as such, leading to dose discontinuations or dose reductions. At the end we decided that many of these patients may benefit from a lower dose and they may not require as much discontinuation and we still have some benefit. So we gave them a lower dose of 37.5mg rather than the standard 50mg and we found that when we followed them up, and we looked at a whole cohort of about 100 patients, that there was no, or little, difference between both the groups, those on 37.5 versus 50. In this particular study we looked at a subset of patients who were older than 65 years, so the older cancer patients, and we found that it was similar as well. Those who were given a lower dose, the 37.5, derived a similar benefit when compared to the younger cancer patients. But we did find that in spite of them being given a lower dose and similar efficacy, some of them did have more discontinuations.
Were the effects of the medication irrespective of age group?
That was irrespective of age group but when we compared the above 65s and those younger than 65 again there was no difference in efficacy in spite of higher discontinuations in the dose above 65.
I think one of the key messages would be that older patients are definitely unique as a group and we may need to consider a lower dose and not deny them treatment because they seem to derive the same benefit. Also another message would be even if we have to dose reduce in this group it is better for them to be on the drug at a lower dose than be off it. Of course there will be a group of patients that may require dose discontinuation due to toxicities, however, we don’t have predictors as to who that particular group is going to be. So you may have to start on the drug first and see how you tolerate it. But if you do tolerate well you’re going to do well.
What recommendations would you make to cancer clinicians?
If you have a patient older than 65 years old, first of all you’ve got to assess the patient in terms of their physical functional status. Number two, start at the lower dose, 37.5mg daily for four weeks on, two weeks off, rather than the 50mg and then assess the toxicities. If they do tolerate it well you can continue on on the same dose and patients are going to benefit from it with a reasonably tolerable side effect profile.