So you can summarize then that induction chemotherapy is established, that concomitant chemo-radiotherapy is probably also established and may be even a little bit better, but we don’t know yet. I think the RTOG trial is important for that. And that we now need to integrate the new drugs and maybe find out; is induction better than concomitant, but should maybe both be given? This is the first such trial that tried to evaluate should both be given, giving induction and then radiation versus radiation with weekly carbo at low doses. So this is going back to the single agent concept. And you see no difference. That’s actually consistent with cisplatin literature, that single agent radiation sensitization is simply not enough to make a difference. Median survival, 13 months in both arms as you would expect in an induction chemotherapy trial.

In CLGB we’ve now looked at giving induction and concomitant but multi-agent therapies. And several other groups are looking at this and then adding the new drugs into this menu. We have some preliminary data that suggests that this can be done. We’ve looked at gemcitabine in this setting, paclitaxel and vinorelbine. All three are feasible but how good they are and what kind of long term survival rates we get, we are not sure of yet. So this was a randomized phase II trial, about 60 patients per arm, and we do now that all three arms are feasible and that these new drugs may have a role in stage III disease, much as they do in stage IV disease.

So in the last few minutes then, let’s move down to the earlier stage disease settings. If chemotherapy has a role in stage IV for palliation and in stage IIIb to increase survival, then moving to the earlier stages you have fewer patients to evaluate, you bring in surgery as a third modality, randomized trials are very few and the conclusions are much less clear. So I just want to leave you with a few impressions. This is stage IIIa disease where again you have large primary lymph nodal disease but usually the surgeon has an option of at least attempting a curative intent resection. There have been two very small trials that are frequently cited that have looked at induction chemotherapy for stage IIIa disease and in this case surgery versus chemotherapy, followed by surgery. If you look at the three year survival there was a large difference favoring induction chemotherapy. A very similar trial from Spain, published in the New England Journal 1994, again about 30 patients – these are much harder to do these trials than stage IV or IIIb – surgery followed by radiation, versus chemotherapy followed by surgery and radiation. You look at the median survival, eight versus 26 months, and again a suggestion also of long term benefit. But both are very small trials and I could show you similar small trials that did not show that benefit. So for IIIa disease, induction chemotherapy, we’re really not sure yet.