HAMBURG, GermanyGLOB-1 trial results, reported at the 25th
Congress of the European Society of Medical Oncology (ESMO), have
confirmed the combination of vinorelbine (Navelbine) and cisplatin
(Platinol) as a chemotherapy reference standard in metastatic
non-small-cell lung cancer (NSCLC), raising questions about the role
of three-drug combinations in this setting.
GLOB-1 investigators in 16 countries randomized 257
chemotherapy-naïve patients with stage IV or relapsing NSCLC to
vinorelbine (30 mg/m² on days 1, 8, and 15) plus cisplatin (80
mg/m² on day 1) or vinorelbine (25 mg/m² on days 1 and 8)
plus cisplatin (75 mg/m² on day 1) plus ifosfamide (Ifex) (30
g/m² on day 1), given every 21 days.
The addition of ifosfamide failed to enhance the objective response
rate (36% with triple-drug therapy vs 36% with two drugs) or disease
control (60% vs 65%), reported Pierre-Jean Souquet, MD, of South Lyon
Hospital Center, Pierre-Benite, France. Although the two-drug
combination appeared to result in prolonged survival (43 weeks vs 36
weeks), Dr. Souquet cautioned that this difference did not reach
The absence of gain with ifosfamide might have been attributable to
the lesser dose intensity of vinorelbine achieved with the three-drug
regimen, suggested discussant Nicholas Thatcher, MD, of Christie
Hospital, Manchester, UK.
Dr. Thatcher underscored the need to identify two-drug combinations
for NSCLC that are less toxic, less expensive, can be given weekly in
lower doses, and perhaps eliminate the need for platinum altogether.
The time has come to use newer drugs such as gemcitabine
[Gemzar], taxanes, oral vinorelbine, and topotecan [Hycamtin],