Neoadjuvant cisplatin chemotherapy before chemoradiation: a flawed paradigm?

Effective chemotherapy (CT) treatment of solid tumors emerged with the introduction of anthracyclines and platinum CT in the late 1970s, at first with palliative intent, and later extended into the adjuvant setting. High response rates led to the belief that systemic CT might improve locoregional control and also decrease the risk of distant metastases. A new strategy advocated cisplatin-based neoadjuvant CT (NACT) before definitive local treatment-either surgery or radiotherapy (RT). Response to NACT was viewed as a favorable prognostic sign, which allows the selection of patients most likely to benefit from RT or chemoradiotherapy (CRT). The aim of this discussion is to raise the debate regarding NACT in reducing metastases, improving local control and selecting out good responders for nonsurgical treatment in the following sites: head and neck, esophagus, cervix, anus, nasopharynx, and bladder; as well as non-small-cell lung cancer. NACT has almost invariably failed to deliver an improved outcome in terms of disease-free survival (DFS) or overall survival (OS) when delivered before RT or CRT in all solid tumor sites. The evidence that NACT may improve outcome in terms of DFS or OS is strongest when it is administered before surgical resection, but remains scant before RT or CRT. Taxane-containing regimens look more promising than does cisplatin NACT, but have not been shown to improve on concurrent CRT. Future meta-analyses should compare induction CT followed by RT and induction followed by CRT versus RT or CRT alone.