SAN FRANCISCO, CA USA (UroToday.com) - In this talk Dr. Christopher Sweeney addressed evolving treatment strategies in patients with poor-risk metastatic germ cell tumors (GCTs).
While bleomycin, etoposide, cisplatin (BEP) (+/- post-chemotherapy surgery) results in greater than a 90% chance of cure in patients with good-risk metastatic GCTs, its efficacy in poor-risk disease is more limited. Dr. Sweeney commented that outcomes in poor-risk disease now are likely better when compared to the late 1990s given better supportive care aids (e.g., GCSF and anti-emetics), and the emergence of improved salvage chemotherapy. However, within poor-risk disease, a dichotomy of patients exists, with some patients demonstrating “less-poor” risk and others demonstrating “poor-poor” risk. A lack of a significant decline in tumor markers on therapy has been shown in numerous reports to portend a poor outcome. Multiple trials attempting to improve on BEP/VIP outcomes in this group of patients through combination therapy, increased dosage, or the addition of new agents have failed to provide convincing evidence of improved PFS or OS.
Dr. Sweeney then focused on the GETUG13 phase III trial which examined the use of early chemotherapy switch to a complex dose-dense chemotherapy regimen in patients demonstrating slow tumor marker decline after one cycle of BEP in comparison to continued BEP therapy. The dose-dense regimen demonstrated a statistically significant increase in PFS at 3 years in comparison to continued BEP therapy (59% vs 48%). Neurotoxicity greater than or equal to grade 2 was experienced at higher rates in the dose-dense group (23% vs 4%), however salvage high-dose chemotherapy and bone marrow transplant were used at a significantly lower rate in patients undergoing dose-dense therapy (6% vs 16%).
Dr. Sweeney discussed that one of the primary concerns with the adopting of the GETUG13 dose-dense chemotherapy regimen as standard practice is whether or not its complexity exceeds the feasible threshold for application in everyday clinical practice. While in Scandinavia, via the SWENOTECA project, the application of early chemotherapy switch has been demonstrated to be feasible, in the US it has not been adopted by national guidelines and thus is not considered the current standard of care for patients with poor-risk metastatic disease and slow tumor marker decline.
Dr. Sweeney discussed that if the early chemotherapy switch is not to be adopted, then something must fill its void. Clinical trials examining less intense regimens will be vital in pushing treatment of these patients forward. Dr. Sweeney highlighted the 3 current clinical trials being performed in this group of patients utilizing either dose dense BEP, TIP or CBOP-BEP. He concluded by pointing out the importance of developing an international cooperative in order to complete phase III trials examining outcomes with new therapeutic regimens in poor-risk patients.
Highlights of a presentation by Christopher Sweeney, MBBS at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Dana-Farber Cancer Institute, Boston, MA USA