ASCO: Dose-Dense Chemo Effective in GETUG 13 CHICAGO -- Dose-dense chemotherapy is a new standard for the treatment of poor-prognosis germ-cell tumors, a researcher said here. In the phase III GETUG 13 trial, dose-dense chemotherapy reduced the risk of progression or death by 34% (P=0.05) in poor-prognosis patients with slow tumor marker decline, compared with the current standard of care, reported Karim Fizazi, MD, PhD, of the Institut Gustave Roussy, France.The current standard for poor-prognosis germ cell tumors involves four cycles of bleomycin, etoposide, and cisplatin (BEP), he said at the Genitourinary (Nonprostate) Cancer Oral Abstract Session at the annual meeting of the American Society of Clinical Oncology. An early switch in chemotherapy regimen for patients with slow tumor marker decline is the new standard [for these patients], Fizazi said. The trial involved 263 patients with poor-prognosis germ-cell tumors, defined as advanced nonseminoma and: Elevated serum tumor markers (human chorionic gonadotropin [hCG], alpha-fetoprotein [AFP] and lactic dehydrogenase [LDH]) Nonpulmonary visceral metastases Primary mediastinal nonseminoma germ-cell tumorsPoor-prognosis germ cell tumors have a 41% 5-year progression-free survival rate and a 48% 5-year overall survival rate, Fizazi said. In the new study, we aimed to personalize treatment, he said. Patients with predicted poor outcomes based on unfavorable tumor marker decline were selected for experimental treatment that individualized cumulative doses of bleomycin, Fizazi said. Our working hypothesis was that patients would get a small and incremental benefit from paclitaxel, ifosfamide, and increased oxaliplatin dose intensity -- and that the dose-dense regimen would also prevent toxic deaths from neutropenic fever and secondary leukemia, he said. All patients were treated with one cycle of BEP. After 3 weeks, 51 patients with favorable tumor marker decline received another three cycles of BEP, while 203 patients with unfavorable decline were randomly assigned to receive dose-dense chemotherapy (105 patients) or continued to receive three further cycles of BEP (98 patients). The dose-dense regimen consisted of two cycles of paclitaxel, oxaliplatin, and BEP, followed by two cycles of cisplatin, ifosfamide, and bleomycin. The primary endpoint was progression-free survival. In the randomly assigned patients with an unfavorable serum decline, the 3-year progression-free survival rate was 59% in those receiving dose-dense chemotherapy, compared with 48% for BEP (HR 0.66, 95% CI 0.44-1.00; P=0.05). For the secondary endpoint, the 3-year overall survival rate was 73% for the dose-dense arm versus 65% for the BEP arm (P=0.34). Adverse events were generally similar between the two arms, although patients receiving dose-dense therapy were more likely to experience greater than grade 2 neurotoxicity: 23% versus 4% for patients receiving BEP. Discussant Carsten Bokemeyer, MD, of University Hospital Hamburg, Germany, said, This is the first time that a randomized study has shown benefits of therapy intensification for patients with poor marker decline and confirms data from subset analyses of other trials in the poor-risk setting. He noted, however, that the dose-dense regimen used in the French study is not typically used elsewhere. Other options that are worthy of consideration and further study include a high-dose regimen that includes carboplatin, etoposide and cyclophosphamide as well as a paclitaxel, ifosfamide, and cisplatin (TIP) regimen, Bokemeyer said.
Posted on: Sun, 26 Jan 2014 11:33:33 +0000
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