Head & Neck Cancer

Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of locoregional recurrence in diseases like non–small-cell lung cancer (NSCLC) as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can, in certain circumstances, provide an effective means of delivering therapeutic genes to tumor cells. Although multiple genes are involved in carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumors. Preclinical studies both in vitro and in vivo have shown that restoring p53 function can induce apoptosis in cancer cells. High levels of p53 expression and DNA-damaging agents like cisplatin (Platinol) and ionizing radiation work synergistically to induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy using both retroviral and adenoviral vectors is feasible and safe. In addition, p53 gene replacement therapy induces tumor regression in patients with advanced NSCLC and in those with recurrent head and neck cancer. This article describes various gene therapy strategies under investigation, reviews preclinical data that provide a rationale for the gene replacement approach, and discusses the clinical trial data available to date. [ ONCOLOGY 13(Suppl 5):148-154, 1999]

Tumors of the head and neck continue to pose challenges for afflicted patients and their treating physicians. Because the complex and vital anatomy often involved affects the ability to communicate and interact socially, head and neck tumors can have a devastating effect on the patient’s quality of life. Due to the inherently complex nature of such tumors and their rarity, a comprehensive textbook devloted to their management is certain to be useful.

Single-agent, intratumoral gene therapy that targetsthe p53 gene is well tolerated and shows evidence of antitumor activity in patients with recurrent squamous cell carcinoma of the head and neck, according to the preliminary results of phase II clinical

ROCKVILLE, Md-The FDA has approved Ethyol (amifostine for injection) as a therapy to decrease the incidence of moderate-to-severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer. The approval came only 2 weeks after the Oncologic Drugs Advisory Committee (ODAC) recommendation.

The 14 reports in this special supplement discuss theuse of the cytoprotectant amifostine in patients withcancer of the head and neck, esophagus, lung, andcervix, as well as those with lymphoma and acutemyelogenous leukemia. Discussions focus on thepotential of this agent to both reduce radiation sideeffects such as xerostomia and permit doseescalation of chemotherapy and/or radiotherapy.Improvements in treatment outcome and quality oflife as a result of cytoprotection are examined.

n PHILADELPHIA-Vitamin supplements have been shown to have a possible protective effect against mutations of the p53 gene in head and neck cancer, Bruce J. Trock, PhD, director of Molecular Epidemiology, Georgetown University Medical Center, said at the American Association for Cancer Research annual meeting. The multicenter, collaborative study also included scientists from Fox Chase Cancer Center and Temple University Medical Center.

ASCO-Delivering normal copies of the p53 tumor-suppressor gene directly into lesions is a novel and promising approach to treating squamous cell carcinoma of the head and neck, John Nemunaitis, MD, of PRN Research Inc., said at the Annual Meeting of the American Society of Clinical Oncology.

Head and neck imaging, in its current form, really began with the development of the computed tomographic (CT) scanner in the late 1970s and early ’80s. Originally, only CT scans of the brain were performed because of constraints on gantry size.

Modern head and neck imaging has led to advances in both the diagnosis and treatment of head and neck cancers. Both computed tomography (CT) and magnetic resonance imaging (MRI) studies provide important information

Intracranial germinomas are uncommon tumors. In the past, patients have traditionally been diagnosed with a trial of focal radiotherapy without biopsy. If the tumor was radiosensitive, it was presumed to be a germinoma.

During the past decade, federal health agencies have focused on reducing the incidence of oral and pharyngeal cancer and increasing the 5-year survival rate from these cancers in the United States. Beginning with a consortium of health agencies in

Findings that tissue levels of two proteins correlate closely with the prognosis of head and neck cancer may significantly alter the detection, staging, and treatment of this disease, according to an article published in the June 3rd issue of the Journal of

TORONTO--The use of whole-body fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) offers an opportunity to improve the outcome for patients with advanced head and neck cancers. Two papers presented at the 45th annual meeting of the Society of Nuclear Medicine found that FDG-PET was more accurate than conventional imaging for the diagnosis of regional and distant recurrence.

The common clinical presentations of head and neck cancer include early (stage I or II) disease, locally or regionally advanced (stage III or IV, M0) disease, and recurrent or metastatic disease (< 5% of patients).

LOS ANGELES--A genetically engineered adenovirus that replicates in and kills tumor cells deficient in p53 tumor suppressor gene activity has shown promising results in patients with advanced head and neck cancer, David H. Kirn, MD, said at an ASCO poster session. Dr. Kirn is director of clinical research at Onyx Pharmaceuticals, Richmond, California, which is developing the new agent, known as ONYX-015.

TORONTO--Therapeutic strategy in patients with head and neck cancer is sometimes based on the staging of regional lymph nodes. However, standard imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) cannot differentiate between inflammation and metastasis in an enlarged lymph node and may not discover distant disease.

Management of patients who have head and neck cancer necessitates a multidisciplinary approach.[1,2] Comprehensive care must be initiated prior to therapy, maintained throughout course of treatment, and systematically coordinated for the rest of the patient’s life. As Dwyer and Minasian note, a multidisciplinary team that includes dental professionals, a speech/language pathologist, and a registered dietician is best suited for this complex management challenge. These individuals, working in conjunction with physicians, nurses, and other professionals, can provide patients with key preventive and therapeutic supportive care interventions.

he authors are to be commended for providing an overview of several important, though often overlooked, management issues in head and neck cancer. In their overview of nutrition, they correctly state that the nutritional status of head and neck cancer patients is frequently compromised even before cancer diagnosis and treatment. Documented reasons for this include poor oral hygiene, ill-fitting dentures, and a high incidence of alcoholism.[1] Consequently, it is imperative that patients’ pretreatment nutritional status be determined so that necessary dietary modifications can be made prior to therapy. As the authors emphasize, nutritional reassessment and intervention should continue during and after treatment.

Tumors of the head and neck account for 4% of cancers in the United States. Both the disease process itself and side effects of cancer treatment, such as xerostomia, dysphagia, and malnutrition, compromise oral health,

An ideal diagnostic test for cancer would be noninvasive and provide accurate results with sufficient specificity and sensitivity. Currently, no test for cancer meets all of these criteria. However, results of a study presented at the annual meeting of the

DURHAM, NC--Use of amifostine (Ethyol) significantly reduces the incidence of chronic as well as acute xerostomia and associated symptoms in patients undergoing radiotherapy for the treatment of head and neck cancer, David Brizel, MD, associate professor of radiation oncology, Duke University Medical Center, said at the ASCO meeting.

PROVIDENCE, RI--Weekly chemotherapy with carboplatin (Paraplatin) and paclitaxel (Taxol) followed by irradiation resulted in a 91% overall response rate in patients with inoperable cancer of the head and neck.

NEW ORLEANS--A diagnostic test under development may be able to detect many head and neck squamous cell carcinomas while they are still in their early stages, David Sidransky, MD, professor in the Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, reported at the 89th annual meeting of the American Association for Cancer Research.

Results of treatment for patients with salivary gland carcinoma have improved in recent years, most likely due to earlier diagnosis and the use of more effective locoregional therapy. Salivary gland tumors are treated surgically, often in conjunction with postoperative radiation therapy when the tumor is malignant. Good results rest strongly on the performance of an adequate, en bloc initial resection. Radical neck dissection is indicated in patients with obvious cervical metastasis, and limited neck dissection may be appropriate in patients with clinically negative nodes in whom occult nodal involvement is likely. Postoperative radiation therapy should be administered when the tumor is high stage or high grade, the adequacy of the resection is in question, or the tumor has ominous pathologic features. Neutron beam therapy shows promise in controlling locoregional disease but requires further study. No single chemotherapeutic agent or combination regimen has produced consistent results. At present, chemotherapy is clearly indicated only for palliation in symptomatic patients with recurrent and/or unresectable cancers. Patients with salivary gland carcinomas must be followed for long periods, as recurrence may occur a decade or more following therapy. Distant metastasis appears to occur in approximately 20% of patients.[ONCOLOGY 12 (5): 671-683, 1998]

n ORLANDO-Amifostine (Ethyol) given prior to radiation therapy in head and neck cancer patients significantly reduced the incidence of radiation-induced grade 2 xerostomia. Mucositis was not a dose-limiting toxicity, and patients generally were able to receive their scheduled radiation doses without delays,

Ms. Clarke provides an excellent overview of the rehabilitation process for the head and neck cancer patient. She highlights pretreatment and posttreatment rehabilitation issues and details the nature of each multidisciplinary intervention. I concur with the rehabilitation process that she describes and second the importance of multidisciplinary interventions beginning prior to treatment.

Although head and neck cancer accounts for only about 5% of all malignancies, the functional and cosmetic changes that result from the tumor or its treatment pose a challenge to the health-care community. In today’s health-care environment, we are being forced or at least encouraged to decrease the length of hospital stay for patients following all types of surgical procedures. As a result, the inpatient census for most units has decreased substantially, causing many specialized patient care units to close.

As the economics of health care increasingly dictate the parameters of patient care delivery, the role of rehabilitation has taken on new meaning with regard to positive patient outcomes. This is particularly true for the head and neck cancer patient coping with devastating physical and functional changes. With treatment advances leading to increased survival, health-care providers must therefore focus on restoring function and assisting the patient to achieve an acceptable quality of life. For the head and neck cancer patient with multiple rehabilitation needs, this can best be accomplished through a comprehensive, coordinated approach, utilizing interdisciplinary clinical and community resources aimed at facilitating the rehabilitation process and ultimately achieving individualized rehabilitation goals.

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.

In 1970, Ansfield and colleagues published the results of a randomized trial in head and neck cancer, which showed that giving fluorouracil (5-FU) concomitantly with radiation decreased regional recurrences and improved overall survival over radiation alone.[1] Publication of these results came 6 years before those of an Italian trial showing similar findings with adjuvant cyclophosphamide, methotrexate, and 5-FU (CMF) in breast cancer.[2] Yet, while adjuvant chemotherapy has rapidly become the norm in the management of early breast cancer, concomitant chemotherapy is still considered undefined in the treatment of head and neck cancer. This situation is elegantly described by Dr. Karen Fu, one of the most respected investigators in this area.