Clinical promise tempered by reality in the delivery of combined chemoradiation for common solid tumors

Until quite recently, there was no firmly established role for cytotoxic chemotherapy in the curative management approach for many of our most common malignancies. Systemic therapy was often reserved for recurrent or metastatic disease after initial surgery and/or radiotherapy. Today, the treatment of many advanced cancer patients involves integration of chemotherapy into the definitive treatment strategy. This evolution in therapy is largely a reflection of the clinical trials process that has defined clinical benefit for the addition of chemotherapy in several settings. This is good news overall. It validates years of preclinical experimentation that predicted advantage in combining chemotherapy with radiation. Moreover, with a primary objective to increase cancer cure rates, we now see confirmatory evidence across a spectrum of recent clinical trials. Tempering this good news is the fact that these gains are often quite small. They are commonly accompanied by increased toxicity and are generally achieved in good performance status patients who may not accurately reflect the broad cancer population. In addition, the first generation of positive trials for a particular disease site are often accomplished with vastly differing treatment regimens. This frequently leaves the general oncologist to query "which specific approach is best?" In this article, we briefly trace the evolution of current therapy approaches in 2 common human solid tumors, namely cancer of the head and neck and non-small-cell cancer of the lung. The focus involves the development of chemoradiation strategies in the definitive treatment setting. Clearly, surgery plays a critical role in treatment for many patients in these anatomic categories. However, we lack randomized trials that directly compare operative versus nonoperative treatment approaches and thus have consciously neglected review of the surgical series for purposes of this article.