What is happening for at least N2 IIIa disease right now is a very important trial that accepts concomitant chemo-radiotherapy – that’s the SWOG regimen, platinum, etoposide, radiation – and then asks, “Do these patients really need surgery? Do they benefit from that or is chemo-radiotherapy just as good?” So they randomized on the standard arm to receive 45 gray of radiation with two cycles of platinum, etoposide and then surgery versus that same initial chemo-radiotherapy and then a chemo-radiotherapy boost. This trial is in progress and hopefully will complete in the very near future.
What about classical adjuvant chemotherapy for earlier stage disease, stage I or stage II? This is a very typical design. You would look at surgery and radiation, in some cases surgery alone, versus surgery, radiation and chemo. Well, to make it brief, to date there is no proven role for adjuvant chemotherapy. I’m showing you this trial as the most recent example of a negative trial. This was a large U.S. intergroup trial, designed just as this: surgery, radiation, surgery, radiation with platinum, etoposide. Two cycles concurrent and two cycles adjuvant afterwards. Preliminary analysis shown at ASCO this year, long term follow-up already. Median 41 months and median survival identical, 38 months on both arms. The only thing that is encouraging about this is that the median survival was really high on both arms. Surprisingly so, maybe, and the five year survival rate particularly encouraging at 39% and 33%. But this does not support a role for adjuvant chemotherapy, not yet.
This is a positive trial, a European trial, that actually suggests that induction chemotherapy may be of benefit in stage Ib to IIIa where patients had either surgery or MIP, mitomycin ifosfamide, platinum, and then surgery. And radiation was given to some patients according to individual preference. In this trial, if you look at the two and three year survival, there is a suggestion of benefit. But it’s confounded by a number of things. The number of patients getting radiation on the surgical arm is much higher and paradoxically we now think that adjuvant radiation for at least some of these patients actually decreases their chances of survival or cure rather than increasing it. That’s again fairly recent literature looking at the role of radiation. So I’m showing you this to say that not all data are negative, but it’s certainly not yet conclusively supporting induction chemotherapy.
Now finally then, looking at current affairs here, here in early stage disease – much like in the advanced stages – we are looking at the newer regimens and what is called the bi-modality lung oncology trial, or BLOT. Bi-modality because it is chemo and surgery, looks at induction chemotherapy with carboplatin and paclitaxel in stage Ib through IIIa disease. This has been piloted in 94 patients with an objective response rate of the chemotherapy of 54%, which is not bad, and based on this the phase III trial has been activated where patients received either surgery or induction, not adjuvant, carbo and paclitaxel for three cycles.