NEIL LOVE, MD: What are your thoughts about the concept of achieving the optimal benefit with VEGF tyrosine kinase inhibitors by delivering as much of the planned dose as possible?
NICHOLAS J VOGELZANG, MD: The available data are not definitive, but we have reported data from a population of patients in whom blood levels of sunitinib were measured. A strong association was observed between the dose delivered and blood levels of sunitinib, which were correlated with response, duration of response and survival.
We also have data from the Phase II study with continuous daily sunitinib that was recently published in the Journal of Clinical Oncology. The progression-free survival (PFS) was inferior to the 50-mg four week on, two week off schedule of sunitinib published in The New England Journal of Medicine, but the patients in this Phase II study were comprised of a slightly worse prognostic group. So I’m not certain that you can compare apples to oranges.
DR LOVE: The median PFS was 8.2 months and overall survival was 19.8 months.
DR VOGELZANG: That’s correct, and I would point out that this study was conducted between 2005 and 2006, and the only agent available at crossover was sorafenib. We didn’t even have the mTOR inhibitors, which I suspect will improve overall survival.
I am eager to see the results of a randomized, Phase II trial (Renal EFFECT Trial), which compares standard sunitinib 50-mg/daily four weeks on, two weeks off to continuous daily dosing of sunitinib 37.5 mg. In evaluating the pharmacokinetic area under the curve, continuous should be as effective as the intermittent schedule.
DR LOVE: What was your perception of the side effects with continuous dosing?
DR VOGELZANG: I’m a biased investigator. I examine my patients and think, “Hmm. This is going well. I’m pleased with this toxicity parameter.” I need to see a direct comparison. In my practice if patients experience excessive toxicity with the 50-mg (four-on, two-off) schedule, then I will automatically drop them to 37.5 mg/day continuous dosing.
DR LOVE: Another schedule I’ve been hearing about is two weeks on, one week off. What are your thoughts about that?
DR VOGELZANG: I don’t believe that’s a good idea. Many strategies exist to ameliorate toxicity. I believe duration of exposure is probably important, and continuously inhibiting the angiogenic signal from the kidney cancer cells to the normal endothelium, which is what sunitinib does, should be important. It should be continuous suppression of angiogenesis.
Dr Vogelzang is Chair and Medical Director of the Developmental Therapeutics Committee and Co-Chair of the Genitourinary Committee for US Oncology Research via Comprehensive Cancer Centers of Nevada in Las Vegas, Nevada.
