And you see there are at least four, all asking basically the same thing and all coming to the same conclusion. This is the best one, British Medical Journal, 1995. Median survival six months with supportive care, eight months with chemotherapy. One year survival, 16% versus 26%. All four concluded that chemotherapy improved survival by a little. This is a more recent example. MIC, standing for mitomycin, ifosfamide, cisplatin; the British trial, published this month in JCO. And here four cycles of MIC versus best supportive care: median survival, five versus seven months, statistically significant. I show this trial and the data are in the Journal because they looked at quality of life and it was improved with chemotherapy over best supportive care. This had also been addressed in previous trials, but addresses this issue where frequently it was meant that yeah, you only improve survival a little and are patients really benefiting from it? Well, they do.

What about elderly? This is a disease that frequently occurs in the elderly. So patients 70-years-old, or in the past it would be argued, “Well, let’s not treat that patient anymore. It’s too old.” Well, 191 patients were randomized to either vinorelbine single agent or best supportive care. Median survival with chemo: 27 weeks versus 21 weeks. Sort of showing the same thing in this group of patients. Six months survival: 54% versus 39%, statistically significant. One year: 27% versus 5%. Quality life here too was analyzed – this was published in JMCI last year, or early this year rather – improved with chemotherapy. Finally, cost-effectiveness has been looked at, particularly with one of these trials, the so-called Canadian trial. And to not go into great detail, just to make the case, that even though the chemotherapy costs some money they felt that this was well within the range of any other interventions and that cost or cost-effectiveness should not be a barrier to offering chemotherapy. So looking at this information, you can summarize that chemotherapy is an active modality in stage IV disease, that it prolongs survival by a little, that it improves quality of life – and it does so at acceptable cost – and as a consequence should be offered to these patients. The debate is done. That’s the literature of the 80’s.

So what we want to move onto then is in the 90’s, not much any more do we want to use chemotherapy but can we identify better chemotherapy? I mentioned that there were five drugs that came out during this decade. They have now been somewhat evaluated and let’s go over that a little bit, in sequence at least. The first two trials will focus on vinorelbine. That was the first drug that came out. It’s a Vinca alkaloid. This is the definitive trial done by SWOG, Tony Wosniak published in JCO. Cisplatin alone is the control arm, cisplatin, vinorelbine was the experimental arm. Median age 63 years as a standard. Most patients male, as is the case, and most had stage IV disease. So this is a poor prognostic group of patients. Some other trials have more patients with stage IIIb disease in there. You can look at response. So what’s the single agent response rate to cisplatin? It’s 12% and to cisplatin and vinorelbine it’s 26%. Here’s the overall survival: median survival six months with cisplatin alone and about eight months with cisplatin and vinorelbine and statistically significantly improved. So this is the trial, or one of them, that got vinorelbine approved by the FDA for non-small cell lung cancer, and cisplatin, vinorelbine then as a possible standard regimen.