Now have any of these new regimens been compared amongst themselves? This is a SWOG trial that was presented at ASCO this year, looking at cisplatin, vinorelbine versus carbo and Taxol in this case. And what it showed is that response rates were similar at 28% and 25%. This is cisplatin, vinorelbine. Carboplatin, Taxol one year survival 36% and quality of life improved or stable also in about 60%. So this established, as some of us have felt for awhile, that several of these new regimens are probably going to emerge as of equal efficacy. So cisplatin, vinorelbine, carbo, Taxol, cis, Taxol is shown here, but they differ a little bit in their toxicity spectrum. If you look at neutropenia, that was more common with cisplatin, vinorelbine than with carbo, Taxol. If you look at neuropathy, then that was a little more common with carbo and Taxol. So that can guide you sometimes maybe to the choice of regimen.
What about gemcitabine, then? Gemcitabine is also a new active drug. This is the definitive trial for gemcitabine that got that drug approved for non-small cell lung cancer. I failed to mention, Taxol-2 is approved. A large multi-center randomized trial of single agent cisplatin versus cisplatin plus gemcitabine. Not fully published yet but this is data from the abstract, looking at grade II or IV neutropenia, more common with the combination. Same for thrombocytopenia. Response rate was 31% versus 9%, and median survival 8.7 versus 7.6 months with a statistical trend. This has not yet been fully published.
So what about docetaxel then? Docetaxel; there are no completed randomized trials yet as a first line agent but what’s interesting about docetaxel is that it has been evaluated as a second line treatment agent, which is quite unique for non-small cell lung cancer. Remember, we just established that chemotherapy is worth doing first line. Well, second line; it’s been evaluated in a number of phase II trials where response rates were seen as high as about 17%. A multi-center phase II was done and presented at ASCO in 2006 by Dave Kendara, and the response rate there was 15% in patients who had been previously treated, usually with cisplatin-based therapy. So there are now two randomized trials, second line therapy randomized trials that have been presented. They are not fully published yet. This was shown by Dr. Pasella at ASCO this year and they looked at either docetaxel at two doses, high and less high, versus either vinorelbine or ifosfamide and the choice here had to do with prior chemotherapy in that specific patient. When you look at the one year survival, then the low dose Taxol, Taxotere, was superior to the other two arms. That suggests that if you too toxic that can be detrimental but certainly if you look at response rate at 1%, vinorelbine or ifosfamide, docetaxel seemed to be the more promising approach. There is a second trial, docetaxel versus best supportive care in previously treated patients, because we now feel that most patients should get chemotherapy up front. But second line best supportive care trials are probably okay to do. You look at median survival time; 7 months with Taxotere versus 4.7 months with best supportive care. Quality of life – in particular, pain and fatigue – better. So here Francis Shepard who presented this recommended that second line therapy could be given, but again, at the lower Taxotere dose of 75 mg per meter squared. So this is an emerging approach. It is still hard to make generalizations because the prior therapy for many of these patients was not yet what frequently would now include actually a taxane as first line therapy. So if you have it first line, would you use it second line? Probably not.