Loading...
As the cure rate for patients with stage I seminoma approaches 100%, researchers are exploring ways to ameliorate therapy-related toxicity. Adjuvant radiotherapy (RT; 20–24 Gy) has long been administered with excellent results, and, more recently, many investigators have advocated surveillance as a viable management strategy. To examine a third approach to therapy, two European cooperative groups previously initiated a randomized study in which a single dose of carboplatin was compared with radiotherapy in 1477 stage I seminoma patients at 70 hospitals in 14 countries between 1996 and 2001 (Lancet 2005; 366:293). In that study, 904 patients received radiotherapy (RT; para-aortic strip or dog-leg field), and 573 received one injection of carboplatin (dose in mg = 7× glomerular filtration rate + 25). The trial was designed to measure relapse-free rate as the primary outcome and was powered to exclude absolute differences of >3% in 2-year relapse-free rates; at a median follow-up of 4 years, results showed that carboplatin was noninferior to radiotherapy.
Now, at 6.5-year follow-up, only one death from disease has occurred (in the RT group) and significantly fewer new germ cell tumors (GCTs) were seen in patients who received carboplatin than in those who received RT (2 vs. 15; J Clin Oncol 2008; 26:suppl:abstract 1). The results confirm the noninferiority of single-dose carboplatin versus RT in relapse-free survival as well as in reducing risk for developing a second GCT. Questions remain about the long-term risks for developing second cancers and infertility from carboplatin therapy. Among all management strategies, surveillance might be the most important to consider, given that it has minimal risks compared with both carboplatin and RT.
RAD001 (everolimus), an oral inhibitor of mammalian target of rapamycin (mTOR), can inhibit angiogenesis and cell proliferation. In a phase III trial, 410 patients with advanced renal cell carcinoma (with a clear cell component and disease progression after therapy with sunitinib [Sutent], sorafenib [Nexavar], or both) were randomized to RAD001 (10 mg/day) or placebo; 272 patients received RAD001, and 138 received placebo (J Clin Oncol 2008; 26:suppl:abstract LBA5026). Median progression-free survival (PFS), determined by blinded independent review, was significantly longer for patients receiving RAD001 than for those receiving placebo (4.0 vs. 1.9 months). The most common adverse events were stomatitis, anemia, and asthenia. This is the first prospective study to show that an agent provided benefit to patients who had failed to respond to a tyrosine kinase inhibitor.
Initial results from a phase III trial of sunitinib versus interferon alfa (IFN-α) for initial management of metastatic renal cell cancer in 750 enrolled patients showed significantly longer PFS for patients treated with sunitinib than for those treated with IFN-α (11 vs. 5 months; N Engl J Med 2007; 356:115). Sunitinib also was associated with a higher objective response rate than was IFN-α (31% vs. 6%). Given these results, patients in the IFN-α arm were permitted to cross over and receive sunitinib as soon as the benefit associated with sunitinib was determined. Now, the final report from this study indicates longer overall survival for sunitinib-treated patients than for IFN-α–treated patients (median 26.4 months vs. 21.8 months; P=0.051; J Clin Oncol 2008; 26:suppl:abstract 5024). Intriguingly, among patients who did not receive additional post-study treatment, median overall survival was 28.1 months for sunitinib-treated patients (193) versus just 14.1 months for IFN-α–treated patients (162).