Athanassios Argiris, MD

More than 60 years ago, Karnofsky and colleagues reported promising results with the introduction of nitrogen mustard, the prototype of alkylating agents, for the treatment of lung cancer.[1] Subsequent milestones in the development of lung cancer chemotherapy included the use of platinum agents in the 1970s and 1980s, while the 1990s brought several active agents that could be combined with platinum, namely the taxanes, gemcitabine (Gemzar), and vinorelbine.

Squamous cell carcinomas of the head and neck are highly responsiveto induction chemotherapy. However, randomized trials have failedto demonstrate a survival advantage with the addition of induction chemotherapyto locoregional therapy consisting of surgery and/or radiationtherapy. Currently, concomitant radiation and chemotherapy hasemerged as a standard and has optimized locoregional control in headand neck cancer. In this setting, the addition of induction chemotherapymay further improve outcome by enhancing both locoregional and distantcontrol. As interest in induction regimens is renewed, we elected toconduct a systematic review of trials of induction chemotherapy forlocoregionally advanced head and neck cancer. The most studied combination-cisplatin plus fluorouracil (5-FU)-achieves objective responserates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregionaltherapy alone. The introduction of a taxane into induction chemotherapyregimens has produced promising results. Induction chemotherapyshould be the subject of further clinical research in head andneck cancer. Randomized clinical trials in which the control arm isconcurrent chemoradiotherapy and the experimental arm is inductionchemotherapy followed by concurrent chemoradiotherapy are planned.Platinum/taxane combinations are the preferred regimens for furtherstudy in the induction setting and a suitable platform with which toinvestigate the addition of novel targeted agents.

Lung cancer remains the leading cause of cancer death in Americanmen and women. Non–small-cell lung cancer (NSCLC) accountsfor 85% of these cases. Although surgery is the best curative approachfor resectable NSCLC, long-term survival for patients with operabledisease remains poor. More than half of patients who initially presentwith stage I to IIIA disease experience relapse of metastatic disease.Postoperative adjuvant therapy has been evaluated in several randomizedtrials, and provides a survival benefit. It appears reasonable tolook to induction chemotherapy, or preoperative chemotherapy, to providea similar improvement in survival with early treatment ofmicrometastatic disease. Multiple trials of induction therapy have beencarried out with encouraging results. The use of various induction regimenswith chemotherapy alone or chemotherapy combined with radiotherapyfor stage IIIA NSCLC is under investigation. Randomized trialsare under way to better define the role of induction therapy in themultimodality treatment of NSCLC.