A phase II study of oxaliplatin and gemcitabine in advanced inoperable stage IIIB/IV non-small cell lung cancer

McLaren, V., Graham, J., Paul, J. and Dunlop, D. (2008) A phase II study of oxaliplatin and gemcitabine in advanced inoperable stage IIIB/IV non-small cell lung cancer. Journal of Clinical Oncology, 20(5), pp. 384-385. (doi: 10.1016/j.clon.2008.03.007)

Abstract

The current standard of care in non-small cell lung cancer is a cisplatin-containing doublet. However, cisplatin is associated with significant toxicity and inconvenience of administration (with many hospitals still requiring patients to be admitted for pre and post hydration). Even with this combination, the 5-year survival in the advanced setting is <10%. We therefore carried out a phase II study investigating the substitution of oxaliplatin for cisplatin, in combination with gemcitabine, with the aim of decreasing toxicity and improving overall survival. The primary end point of this study was to assess the response rate for stage IIIb/IV non-small cell lung cancer to oxaliplatin and gemcitabine chemotherapy. The secondary objectives of this study were to determine toxicity, treatment delivery, progression-free survival and overall survival. In total, 20 patients were entered into the study (recruitment was terminated early because of the low number of responders according to the criteria of a Simon's two-stage optimal phase II design). Ten (50%) patients had stable disease, two patients (10%) had a partial response and five patients (25%) had progressive disease (95% confidence interval for response rate: 1.2–31.7). Three patients were unevaluable. The median progression-free survival was 3.1 months (95% confidence interval: 1.4–5.8). The median overall survival was 6.9 months (95% confidence interval: 3.1–9.2). All patients have either progressed or died. Thirteen patients had confirmed progression before death. Although the toxicity and ease of administration with this regimen was superior to cisplatin, the response rate was very disappointing and inferior to other quoted studies. A recent study in advanced non-small cell lung cancer showed a superior response rate of 42% vs 34% when using a ‘fixed rate’ dose of gemcitabine; with the patients who received a smaller dose over a longer period responding better than those who received a larger dose over a shorter period (30 min, as in our study). The scheduling in our study may, in part, also explain the poorer response rates seen. There is some evidence of a sequence dependency that favours the administration of gemcitabine followed by oxaliplatin. It seems likely that this happens at the DNA level, as incorporation of the anti-metabolite into DNA may increase platinum binding to DNA. The response rate in our study was significantly lower than we expected for an oxaliplatin-based doublet chemotherapy – although it should be noted that in addition to positive studies using this regimen, less encouraging studies have also been published. It is important for oncologists to be aware of this negative study in order to inform their choice of platinum analogue and especially as other positive single-arm phase II studies have been published that are more favourable of the oxaliplatin–gemcitabine combination. We feel these should be viewed with caution until definitive evidence is available from a randomised trial. In addition, it may be that further work needs to be done to optimise both the scheduling and the sequencing of this combination.

• Item Type: Articles (Letter)
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paul, Mr James
• Authors: McLaren, V., Graham, J., Paul, J., and Dunlop, D.
• Subjects: R Medicine > RC Internal medicine
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Clinical Oncology
• Publisher: Elsevier
• ISSN: 0732-183X