Sequential versus single high-dose chemotherapy
In relapsed or refractory germ-cell tumours, does sequential high-dose carboplatin/etoposide improve survival and reduce treatment-related mortality compared with a single high-dose carboplatin/etoposide/cyclophosphamide course?
Histology scope: Mixed GCT; not a seminoma-only trial.
Trial stopped early because of excess treatment-related mortality in the single high-dose arm.
Sequential VIP + 3 high-dose CE cycles versus 3 VIP cycles + one high-dose CEC cycle, with stem-cell reinfusion.
Long-term reported outcomes
Five-year PFS was 47% versus 45% (HR 1.16; P=.454); 5-year OS was 49% versus 39% (HR 1.42; P=.057). Treatment-related mortality was 4% in the sequential arm versus 14% in the single high-dose CEC arm (P=.01).
The study stopped early for toxicity. The long-term OS difference was not statistically significant at the conventional 0.05 threshold, and the trial does not compare HDCT against conventional-dose TIP.
Interpretation and current guideline context
This randomized study informs how HDCT is delivered, not whether HDCT is superior to TIP. It suggests sequential high-dose CE was safer than the tested single high-dose CEC strategy. It should not be conflated with the IPFSG retrospective comparison of conventional-dose versus high-dose salvage chemotherapy or the TIGER trial comparing TIP with TI-CE.
ESMO–EURACAN 2022 lists VIP/PEI, TIP or VeIP as standard-dose salvage options; the guideline literature recognizes that the optimal first-salvage strategy remains a clinical question. NCCN Testicular Cancer Guidelines Insights Version 2.2025 is also linked for current context.
Primary source
Lorch A, Kleinhans A, Kramar A, et al. Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: long-term results of a prospective randomized trial. J Clin Oncol. 2012;30:800–805. DOI: 10.1200/JCO.2011.38.6391.
PubMed abstract ↗ · Journal source ↗
Evidence review date: 18 October 2026. This page summarizes mixed-GCT evidence and does not claim seminoma-specific comparative efficacy.