CHICAGO ― Individualized treatment intensification based on early serum tumor marker declines is associated with improved progression-free survival (PFS) among men diagnosed with poor-prognosis germ cell tumors (GCTs), report authors of phase 3 trial presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.
“An algorithm of individualized treatment intensification determined by the rate of early tumor marker decline reduces the risk of progression or death in men with poor-prognosis GCT,” reported Karim Fizazi, MD, PhD, of the Institut Gustave Roussy at the University of Paris Sud in Villejuif, France, and coauthors.
Treatment outcomes have not improved for 25 years among patients with poor-prognosis GCT, Dr. Fizazi and coauthors noted. However, previous research has shown that serum tumor marker declines at day 21 are associated with better outcomes. The coauthors therefore sought to test whether or not tumor marker decline could inform treatment strategies and prolong PFS.
After an initial cycle of BEP (bleomycin, etoposide, and platinum), patients’ serum human chorionic gonadotropin hormone and alpha fetoprotein levels were assessed during days 18-21. Of 254 patients who were evaluable at day 21, 51 (20%) had favorable serum tumor marker level declines and 203 (80%) had unfavorable declines, Dr. Fizazi and coauthors reported.
Patients with favorable declines continued BEP therapy for a total of four courses, while patients exhibiting unfavorable declines were randomly assigned to receive either BEP (n=98) or a dose-dense regimen (paclitaxel-BEP plus day-10 oxaliplatin for two cycles, followed by two cycles of cisplatin, ifosfamide, and continuous-infusion bleomycin “depending on lung function,” plus G-CSF [n=105]), the coauthors reported.
“The prognostic value of early tumor marker decline was confirmed: 70% vs. 48% for 3-year PFS (P=0.01), and 84% vs. 65% for overall survival (OS; P=0.02),” Dr. Fizazi and coauthors reported.
Among patients with unfavorable declines, those assigned to the dose-dense therapy group experienced a 3-year PFS rate of 59%, compared to 48% among those receiving continued BEP (hazard ratio, 0.66; 95% CI: 0.44-1.00; P=0.05).
“Three-year OS was 73% and 65% respectively,” Dr. Fizazi and coauthors added.
Grade 2+ neurotoxicity (21% vs. 4%) was seen among patients in the dose-dense group but neutropenia and toxic deaths were comparable between the dose-dense and BEP groups (17% vs. 17% and one death each, respectively), the coauthors reported.
“Salvage high-dose chemotherapy plus stem-cell transplant were required in 6% of patients in the unfavorable dose-dense arm and 16% in the unfavorable BEP arm (P=0.01),” they noted.