This is the second trial, a French study. Control arm here was cisplatin with vindesine, an 80’s type of platinum Vinca, versus cisplatin, Navelbine versus Navelbine alone. And this is the outcome: median survival 40 weeks with cisplatin, vinorelbine versus 30 weeks with cisplatin, vindesine. And of note, vinorelbine as a single agent very similar. Of course, vinorelbine as a single agent, I just mentioned in the elderly, coming to similar outcome of about 27 weeks median survival. So this is the second trial that established cisplatin and vinorelbine as a possible standard regimen, slightly better than those of the 1980’s.
There is a third trial that did not show that difference but it really didn’t have a control arm. The only control arm with this one was vinorelbine versus cisplatin, vinorelbine and it showed a median survival for both of about 33 weeks.
So let’s move on to Taxol then. This is probably the best of the U.S. trials. This was an ECOG trial early on. The control arm was cisplatin, etoposide. It was compared with cisplatin, Taxol low dose versus cisplatin, Taxol high dose with GCSF. Of note, and I think this is the only such trial, the Taxol here was given as a 24 hour infusion. Not as we would do now, one or three hours. Median survival: 7.6 months with cisplatin, etoposide and close to 10 months with the two Taxol arms, and there was no dose response curve. Meaning that there is probably a threshold value for this drug but not a dose response curve. So this is a trial that suggested that cisplatin, Taxol could also be a standard regimen. This trial has not yet been published, even though it is a few years old. But supposedly it is going to come up pretty soon.
This is a European trial, cisplatin, Taxol versus cisplatin, VM-26. This is a drug that is not available in the United States, teniposide, but these two are also a standard doublet. Published in JCO by _ in 2006. It’s a large study. You see the doses here; cisplatin 80 plus either teniposide or paclitaxel as a three hour infusion. Look at response rate; 28% versus 40% with paclitaxel. And median survival not different but very good on both arms at almost 10 months. One year survival of 41% and 43%. So this trial was actually not positive for survival, although encouraging on both arms, and here the Taxol was chosen as the future arm because it was felt to be less toxic and provide better quality of life, but had some late neuropathy. This is the outcome. You see no difference between the two but somewhat better median survival.