Details

Autor(en) / Beteiligte

• Necchi, A.
• Mariani, L.
• Di Nicola, M.
• Lo Vullo, S.
• Nicolai, N.
• Giannatempo, P.
• Raggi, D.
• Farè, E.
• Magni, M.
• Piva, L.
• Matteucci, P.
• Catanzaro, M.
• Biasoni, D.
• Torelli, T.
• Stagni, S.
• Bengala, C.
• Barone, C.
• Schiavetto, I.
• Siena, S.
• Carlo-Stella, C.
• Pizzocaro, G.
• Salvioni, R.
• Gianni, A.M.

Titel

High-dose sequential chemotherapy (HDS) versus PEB chemotherapy as first-line treatment of patients with poor prognosis germ-cell tumors: mature results of an Italian randomized phase II study

Ist Teil von

• Annals of oncology, 2015-01, Vol.26 (1), p.167-172

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m2), 2 courses of cisplatin and HD-etoposide (2.4 g/m2) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7–165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8–72.8] and 54.8% (95% CI 41.6%–72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9–79.0) and 59.3% (95% CI 46.1–76.3). One toxic death (PEB arm) was recorded. The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. NCT02161692.