Up until very recently, conclusions about the usefulness of chemotherapy among patients with advanced, diffuse BAC had generally been based on retrospective experiences with chemotherapy at a single center with a very limited number of patients. From such limited subsets, it is difficult to tell whether BAC is less responsive to standard chemotherapy than other forms of NSCLC, as is widely perceived, or if chemo is similarly helpful for BAC as for NSCLC in general. Some of these studies suggest a similar response rate in BAC compared to other types of NSCLC, while others suggest that patients with BAC are less likely to respond. Making conclusions has also been a problem because of the difficulty in measuring response of BAC lesions, which are often poorly circumscribed on CT scans that are generally used for response assessment.
The Southwest Oncology Group (SWOG) conducted the first prospectively designed trial for patients with advanced BAC, S9714 (abstract here). This trial included 58 chemo-naïve patients with advanced stage BAC who received a four-day long infusion of taxol (paclitaxel) repeated every 3 weeks. The response rate of 14% and survival averaging a year were accompanied by significant toxicity, with infections and nerve damage, that limited interest in future study of this approach. Another trial done in Europe also tested taxol in advanced BAC, this one using a more common schedule of giving it one day every three weeks (EORTC Taxol in BAC abstract here). The response rate was only 11%, and many patients progressed off of this chemo in just a couple of months, and overall these results were disappointing. Taken together with the retrospective studies, it appears that while conventional chemotherapy may possibly be as good as that seen with NSCLC in general, but since patients with BAC on average have a slower progression than do patients with other types of NSCLC, it was clear that other approaches were needed.
The study of BAC is still in the early stages, and it’s fair to say that we really haven’t tested many types of chemotherapy well in BAC. I and other people have seen encouraging responses of BAC patients with several kinds of chemotherapy, including Alimta (pemetrexed), which is being studied in a clinical trial by SWOG (SWOG 0526)available at many sites throughout the country. In addition, we’ve seen clear activity in BAC with targeted therapies, specifically EGFR tyrosine kinase inhibitors, that have been very encouraging and are described in a separate post.