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New Treatments for Non-Small Cell Lung Cancer

Lung cancer is smoking-related. This is a totally preventable disease if patients do not smoke. And all of what we talked about wouldn’t be necessary if not for cigarettes. So it is the second most common malignancy in both sexes. Head and neck cancer was 40,000, this is 172,000 cases per year and it’s the most common cause of death in either sex.

Now what about the histologic types? Seventy-five percent are non-small cell, that’s what we will cover here. The others are small cell and non-small cell, divided up into these cancers: in the United States now adenocarcinoma is the most common, squamous carcinoma is next. This used to be different 20 years ago but now adenocarcinomas are the common ones and we are not sure why that is. Then this is stage-specific survival. Stage I is a confined disease. These patients are treated with curative intent by resection. Stage II is very similar.

So let’s focus then, for non-small cell lung cancer, on therapy and since most of you are medical oncologists that’s what we want to focus on. About 50% of patients present with stage IV disease. They are treated for palliation, and as I will show you, chemotherapy improves survival and quality of life at acceptable cost. It is now accepted therapy for stage IV disease.

There are two groups. These are the older drugs that were available a decade ago and typical regimens then consisted of cisplatin in combination with vinblastine or cisplatin in combination with etoposide. There was also a so-called MVP regimen of cisplatin, mitomycin and vinblastine. That was a triplet. Since 1990 we have at least five new drugs with significant single agent activity, and I will focus on some of that: vinorelbine, Taxol, paclitaxel, docetaxel, gemcitabine and CPT-11 or irinotecan.

So let’s look at the literature of the 1980’s first because what was established during that decade is that chemotherapy is useful for non-small cell lung cancer. Response rates were around 20-30% with most regimens, median survival times around eight months.

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.

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.

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.

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.

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.

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.

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.