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High-Dose Chemotherapy Does Not Improve Treatment Outcome in Patients With Poor-Prognosis Germ-Cell Tumours: Presented at ECCO-ESMO

By Chris Berrie

BERLIN -- September 23, 2009 -- High-dose sequential chemotherapy followed by autologous haematopoietic stem-cell transplant (ASCT) shows no improvement in overall survival (OS), compared with standard chemotherapy in patients with advanced poor-prognosis germ-cell tumours (GCTs).

Andrea Necchi, MD, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, presented the findings of a multicentre, randomised, open-label, phase 3 trial here on September 22 at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO).

"Despite the very high cure rate, there are still 20% of patients who do not achieve durable complete responses," said Dr. Necchi. The recently defined International Germ Cell Cancer Collaborative Group (IGCCCG) "poor prognosis" category shows 48% OS at 5 years.

Patients with GCTs and poor prognosis according to IGCCCG criteria were randomised to receive 4 cycles of cisplatin, etoposide, and bleomycin (PEB; arm A) or 2 cycles of PEB followed by a sequence of high-dose (HD) cyclophosphamide 7 g/m², followed by 2 courses of PEB combined with HD-VP16 2.4 g/m² each, and HD-carboplatin area under the curve 25 mg/mL x min rescued by ASCT (arm B).

Each PEB cycle comprised cisplatin 20 mg/m²/day for 5 days; etoposide 100 mg/m²/day for 5 days; and bleomycin 30 mg on days 2, 9, and 16.

A total of 46 patients were randomised to the standard treatment and 43 to the HD chemotherapy followed by ASCT (n = 43).

At median follow-up of 33.5 months, Dr. Necchi indicated a significantly lower mean platin dose intensity for standard treatment (17.04 vs 20.62 mg/m²/week; P < .0001).

The complete and overall response rates were lower for standard treatment over HD chemotherapy (46% vs 60% and 66% vs 74%; respectively). However, this did not provide any significance benefit for the primary endpoint of 2-year overall survival (66.8% vs 60.5%; P = .42) or progression-free survival (58.5% vs 55.8%; P = .94).

Patients receiving HD chemotherapy had higher incidences of gastrointestinal disorders and infection (10% vs 58% and 6% vs 88%). "The haematological toxicity was, as expected, greater in the HD [chemotherapy] arm, with a greater number of mean transfusion requirements for red blood cells and platelets," said Dr. Necchi.

All patients were engrafted with a median recovery of platelets and neutrophils of 9 days, and there were no late side effects for sequential HD chemotherapy.

There was 1 treatment-related death was with standard treatment.

While noting that there were no prognostic parameters for durable responses, Dr. Necchi said, "The overall message is that there was no improvement of dose intensification over standard chemotherapy."

However, he added, "The challenge now is to best allocate high-dose chemotherapy in a salvage setting, addressing this treatment to the appropriate category with reliable patient categorisation."

[Presentation title: High-Dose Sequential Chemotherapy Versus Conventional-Dose Chemotherapy as First-Line Treatment for Advanced Poor Prognosis Germ-Cell Tumours: A Multicentre Phase III Italian Trial. Abstract O-7100]

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