The Pharmaceutical Journal
Vol 270 No 7240 p360
15 March 2003

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Journal of the National Cancer Institute abstract (more)

No synergy for vinorelbine and gemcitabine in NSCLC

Combination chemotherapy with vinorelbine (Navelbine) and gemcitabine (Gemzar) appears to confer no advantage over either drug alone for elderly patients with advanced non-small-cell lung cancer (NSCLC), results of a new study indicate (Journal of the National Cancer Institute 2003;95:362).

The authors say that a combination of vinorelbine plus gemcitabine is sometimes used in elderly patients or in patients for whom cisplatin-based regimens are not suitable because of toxicity concerns. "Consequently, the finding that vinorelbine plus gemcitabine is no better than either single agent will be of interest to those involved in clinical practice and will result in savings in terms of costs and toxicty," they add.

The phase III randomised study involved 698 patients aged 70 years or older who were randomised to vinorelbine, gemcitabine, or a combination of the two drugs (see Panel).

The researchers report that compared with vinorelbine and gemcitabine alone, the combination therapy did not improve overall or progression-free survival. They add that combination therapy was also more toxic than either of the single agents (although, vinorelbine alone resulted in the highest rates of grade 3–4 neutropenia).

The researchers suggest that vinorelbine and gemcitabine, although acting through different mechanisms, may have exerted non-synergistic or even antagonistic effects. They add that compliance was only slightly lower for patients treated with the combination therapy and could not account for the observed lack of improvement.

In an accompanying editorial, Dr Paul Bunn, University of Colorado cancer centre, Denver, and Dr Rogerio Lilenbaum, Mount Sinai cancer centre, Miami, point out that the results contrast with those of a previous study that found a survival advantage for patients receiving the two drugs in combination. They add that other studies have shown survival benefits for patients receiving a combination of paclitaxel (Taxol) plus carboplatin compared with either agent alone.

"Taken together, these results indicate that elderly patients with advanced NSCLC can benefit from both single-agent therapy and from some combinations and that both single agents and some combinations can be delivered safely," they say. However, they add that whether some combinations (eg, paclitaxel plus carboplatin) are preferred over single agents cannot be determined from the studies to date. "It is hoped that less toxic targeted therapies given sequentially or in combination will provide further advances in the future," they conclude.

Guidance on the use of gemcitabine, vinorelbine and paclitaxel (as well as docetaxel [Taxotere]) in NSCLC was published by the National Institute for Clinical Excellence in June 2001 (PJ, 16 June, 2001, p803) and by the Health Technology Board for Scotland in September 2001 (PJ, 22 September 2001, p373). Neither considered gemcitabine plus vinorelbine combination therapy.