My last post included studies that demonstrated no additional benefit from giving chemo after concurrent chemo/radiation for locally advanced NSCLC, but it's important to add a qualifier to that conclusion. The studies that have shown an overall favorable result from two cycles, or about 6-7 weeks, of chemo with radiation have thus far primarily been with cisplatin and not carboplatin. As I've mentioned previously, there is some evidence that cisplatin and carboplatin, while related drugs and overall similar in performance, may have some differences, and I wouldn't want to generalize the results in stage III NSCLC from cisplatin to carboplatin and visa versa.

The reason is that cisplatin is unusual among chemo agents in that it can be given at full dose with radiation concurrently. Carboplatin is generally given with paclitaxel when administered concurrently with radiation, and both drugs are given at much lower doses than would be used if patients were not receiving radiation at the same time. The reason is that carboplatin and paclitaxel are very potent radiation sensitizers, and giving these drugs at full dose would likely lead to very significant toxicity problems in the area of the radiation field. So carboplatin and paclitaxel are routinely given at a low weekly dose, which enhances the radiation quite effectively.

The problem, however, is that we're fighting cancer on two fronts: local and distant. I've mentioned this in passing before, but we often need to consider the risk of recurrence within the region of the cancer and also the risk of distant disease. When cisplatin/etoposide or some other cisplatin-based regimens are given with radiation, it's possible to give doses that both enhance the radiation effect locally and also provide systemic, "whole body" treatment against micrometastases outside of the radiation field. Since the great majority of patients with stage III NSCLC have recurrence distant from the main cancer, giving effective systemic therapy is an important consideration. And it's not likely that we're offering that with low dose weekly carbo/paclitaxel with radiation.

We're now recognizing the issue of a third compartment of the brain more and more, since 20-35% of patients with stage III NSCLC develop disease recurrence in the brain first or brain only. We don't have an established role yet for prophylactic cranial irradiation in this setting, but it's something we've been studying because the central nervous system (brain, basically) is a potential sanctuary site for untreated micrometastatic disease. Most of our chemo doesn't seem to get into the brain very effectively due to the blood-brain barrier.

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All of this is basically to say that my conclusion about two cycles of chemo concurrent with radiation being as good as more treatment for stage III NSCLC can only be interpreted as applying to cisplatin. We do have some information about carboplatin-based chemo, generally in the context of induction chemo (chemo before concurrent chemoradiation), and I'll cover that next.