Combined-Modality Therapy for Head and Neck Cancer

In the past, head and neck cancers were felt to be primarily a locoregional control challenge. Distant metastases were not thought to occur frequently. However, the popularity of combined-modality programs emphasizing regional treatment with surgery and radiation in the 1960s enhanced the ability to control the disease at the primary site and within the regional cervical lymphatics. Nevertheless, survival was not improved because treatment failure at distant sites occurred frequently. Apparently, prior treatment programs that did not provide locoregional control masked the ability of this disease to spread to distant sites. Patients died of uncontrolled locoregional disease before they could experience distant metastases.

Recognition that the disease did, indeed, have a systemic component ushered in an era of intense clinical investigation evaluating the potential efficacy of cytotoxic therapy in both enhancing locoregional control and decreasing distant metastases. Chemotherapy, delivered as a single agent or in multiple-drug combinations and used in conjunction with surgery and/or radiotherapy, has been studied for the past 20 years or more.

Dr. Fu has played a leadership role in this clinical research. Her paper does an excellent job of describing the results of clinical trials. It is an invaluable addition to the literature because of its thoroughness and Dr. Fu’s ability to succinctly summarize the findings from what is truly an international literature review.

Information Gleaned from “Negative” Trials

There are some who maintain a skeptical attitude about our ability to control head and neck malignancies. There is no question that the past has produced numerous negative trials. But there is also no question that many of these trials have produced useful information that has served as a foundation for subsequent clinical research, which, in turn, has ultimately advanced this field of oncology. The results of past trials, for example, have helped us better understand the feasibility and toxicities of certain regimens.

Dr. Fu accurately states that the nasopharyngeal carcinoma trial is the only one that has demonstrated an increase in survival. However, there certainly are numerous trials mentioned in this review that have shown a positive impact on disease control, tolerance to treatment, and other parameters. For example, the Head and Neck Intergroup Trial completed in 1990 demonstrated, for the first time, that the use of systemic chemotherapy can produce a statistically significant decrease in distant metastases.

The past 20 years have produced progress in this area. Nevertheless, challenges certainly remain for the future. Many of these multiphase treatment programs have suffered from poor compliance. It is important to recognize that this is primarily a noncompliant patient population and that elaborate, protracted, multiphase treatment programs probably will not be well-received.

Organ Preservation vs Improved Survival

The Veteran Administration’s laryngeal preservation trial provided evidence that can a certain percentage of patients can have their larynges preserved with nonsurgical modalities. However, the interest in extending this approach to nonlaryngeal sites needs to be approached cautiously. Currently available treatments for advanced-stage head and neck cancer produce 5-year survival rates in the range of 30% to 35%. The rate of 5-year survival for patients with advanced laryngeal cancer is dramatically better. It is important that we continue to pursue improvement in survival for some of these advanced-stage nonlaryngeal sites rather than accepting the existing 5-year survival rates as a satisfactory exchange for organ preservation.

This article accurately summarizes the toxicities associated with a variety of organ-preserving treatment programs. In the future, it will be important to develop objective measures that will be useful in assessing the impact of not only the disease but also the treatment on our patients’ quality of life.

Summary

In summary, Dr. Fu should be congratulated for a superb review article. It succinctly sets forth the need for continuing the vigorous pursuit of improvements in the outlook for the unfortunate people afflicted with this disease.