Head & Neck Cancer

Rash is a class effect of HER1/epidermal growth factor receptor(EGFR)-targeted agents, and has occurred with high frequency and ina dose-dependent manner in clinical trials of these agents in cancerpatients. Analysis of phase II trials of erlotinib (Tarceva) in non–smallcelllung cancer, head and neck cancer, and ovarian cancer shows asignificant association between rash severity and objective tumor response.Rash severity was highly significantly associated with survivalin patients with non–small-cell lung cancer receiving erlotinib; mediansurvival in patients with no rash was 46.5 days, compared with257 days in those with grade 1 rash (P < .0001) and 597 days in thosewith grade 2/3 rash (P < .0001). Similarly, for the combined non–smallcelllung cancer, head and neck cancer, and ovarian cancer studies,median survival in patients with no rash was 103 days, compared with191 days in those with grade 1 rash (P = .0001) and 266 days in thosewith grade 2/3/4 rash (P = .0001). Similar findings have been madewith cetuximab (Erbitux) and in some settings with gefitinib (Iressa).The strong association of rash severity with response/survival suggeststhat rash may serve as a marker of response to erlotinib treatment andmay be used to guide treatment to obtain optimal response. Dosingerlotinib at the maximum tolerated dose, which is associated with morefrequent and more severe rash, may improve response rates and survivaldurations. Further study of the potentially important associationbetween rash and outcome of treatment with EGFR-targeted agents isneeded.

Paragangliomas are unusual tumorsof the head and neck butshould be included in the differentialdiagnosis of lateral neck masses.Although malignant paragangliomasare possible, these tumors are usuallybenign. Nevertheless, treatment canlead to great morbidity and possiblemortality. The article by Drs. Hu andPersky addresses a multidisciplinaryapproach to these lesions.

Paragangliomas most commonly occur in the carotid body, jugulotympanicarea, and vagus nerve but have also been reported in otherareas of the head and neck. These tumors are highly vascular andcharacteristically have early blood vessel and neural involvement,making their treatment particularly challenging. Surgery has traditionallybeen the preferred method of treatment, especially in light of recentadvances in technique. However, compared to radiation therapy, it canresult in a higher incidence of cranial nerve dysfunction. Radiationtherapy has the advantage of avoiding the increased morbidity ofsurgery while offering an equal possibility of cure. Part 2 of this articlediscusses radiation therapy as primary treatment of patients who areineligible for surgery and the elderly and infirm. Results with radiotherapyare comparable to those achieved with surgery. The efficacy ofsalvage therapy with either surgery or radiation is discussed, and atreatment algorithm for these tumors is proposed.

We have reviewed with interestthe article by Drs. Huand Persky and would liketo congratulate them on an excellentand comprehensive overview of theevaluation and management ofparagangliomas of the head and neck.Their review begins with an excellentlydetailed description of thedisease and staging work-up. Withmodern imaging, most paragangliomasare convincingly diagnosed basedon typical location (carotid bifurcation,nodose ganglia of the vagusnerve, middle ear along tympanic plexus,or near jugular bulb) and characteristicradiographic appearance(hypervascular, intensely enhancingmass). A tissue diagnosis is usuallyunnecessary for such lesions.

Paragangliomas most commonly occur in the carotid body, jugulotympanicarea, and vagus nerve but have also been reported in otherareas of the head and neck. These tumors are highly vascular andcharacteristically have early blood vessel and neural involvement,making their treatment particularly challenging. Surgery has traditionallybeen the preferred method of treatment, especially in light of recentadvances in technique. However, compared to radiation therapy, it canresult in a higher incidence of cranial nerve dysfunction. Radiationtherapy has the advantage of avoiding the increased morbidity ofsurgery while offering an equal possibility of cure. Part 1 of this two-partarticle focuses on techniques for diagnosing paraganglioma and theindications for and use of surgery as primary treatment. The complicationscommonly associated with surgery are reviewed, and strategies forrehabilitation of affected patients are presented.

Part of the multidisciplinary approach to cancer care involves surgical intervention. This is harmoniously interwoven through the efforts of the surgical oncologist and the reconstructive surgeon. As elegantly pointed out by Drs. Hasen, Few, and Fine, the reconstructive surgeon’s role in the management of malignancy is critical, involving the restoration of form and function. Sometimes, as in breast reconstruction, quality of life is improved by the restoration of form; other times, as in head and neck reconstruction, it is improved by the restoration of form and function. In fact, due to the significant morbidity associated with major ablation of head and neck cancer, such radical surgery would not be feasible without concomitant reconstruction.

Quon and Harrison have performed a considerable service to patients with head and neck cancers by reminding the oncology community that a state-of-the-art treatment team must include state-of-the-art brachytherapy

Drs. Quon and Harrison have written an excellent review on the role of brachytherapy in the management of head and neck cancer. Brachytherapy is a time-honored technique, and the authors have carefully reviewed the pertinent literature extolling its virtues. However, there are many papers that fail to document efficacy of brachytherapy over conventional techniques, demonstrating that, similar to surgery, the technique is both patient- and operator-dependent.

Brachytherapy is a therapeutic modality that may provide a significant improvement in the therapeutic ratio when appropriately applied, and hence, is an appealing treatment strategy for the head and neck. For several

Flavopiridol [2-(2-chlorophenyl 5 ,7-dihydroxy-8-[cis-(3-hydroxy-1-methyl-4-piperidinyl)-4H-1-benzopyran-4-one, hydrochloride] is a semisynthetic flavone with a novel structure compared with that of polyhydroxylated flavones, such as quercetin and genistein.[1] It is derived from rohitukine, an alkaloid isolated from the stem bark of Dysoxylum binectariferum, a plant indigenous to India.[2] Originally synthesized and supplied by Hoechst India Limited, flavopiridol is provided to the Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) by Aventis Pharmaceuticals, Inc.

NEW YORK-A phase III clinical trial of the viral therapeutic agent ONYX-015 is underway in patients with recurrent head and neck cancer, based on promising phase II results, Frank McCormick, PhD, said at an American Society of Clinical

SAN FRANCISCO-A single nucleotide polymorphism at codon 388 in the transmembrane domain of FGFR4 is linked to poor survival in patients with head and neck squamous cell carcinoma. The mutation (Arg388) involves the substitution of an arginine molecule for glycine at this position on the gene. It occurs in 45% to 50% of all humans.

Two studies published recently in the Journal of Clinical Oncology showed promising response rates for docetaxel (Taxotere)-based therapy over existing therapies for several types of cancer

ST. PETERSBURG, Florida-Xerostomia, or mouth dryness, typically seen acutely with head and neck radiation, is also the most common late complication following radiation therapy for head and neck cancer, Avraham (Avi) Eisbruch, MD, said at the LENT (Late Effects of Normal Tissues) IV workshop on late effects criteria and applications. Dr. Eisbruch is associate professor of radiation oncology, University of Michigan Medical School, Ann Arbor.

The activity of docetaxel (Taxotere) as a single agent (overall response rates, 24%-45%) in the treatment of patients with recurrent squamous cell cancer of the head and neck has resulted in the investigation of docetaxel-based doublet and triplet combinations in both the recurrent and neoadjuvant settings. When combined with cisplatin, with or without fluorouracil (5-FU), in the treatment of recurrent disease, response rates of 33% to 44% have been observed for docetaxel, with median survival ranging from 9.6 to 11 months. In the neoadjuvant setting, response rates have been typically greater than 90%, with promising disease-free and overall survival results.

Combined-modality approaches for the treatment of non-small-cell lung cancer (NSCLC), head and neck cancer, and esophageal cancer offer survival benefits by improving locoregional control and treating micrometastatic disease. The taxanes are active, tolerable drugs in these solid tumors and have radiation-sensitizing activity.

The 5-year survival of patients with locally advanced squamous cell cancers of the head and neck is still less than 30%. Treatment of these cancers involves significant functional impairment, diminished quality of life, and considerable time and expense. Local recurrence and distant metastases are still fairly common, and the development of second primary cancers has a significant impact on survival in patients with initial early-stage disease. Despite the success of combination chemoradiation in locally advanced head and neck cancers, these facts stress the need for improved treatment of this disease.

The role of sentinel lymph node identification has been investigated over the past decade in a variety of malignancies. It has become part of standard care for melanoma. Its role in breast cancer is evolving, but with the completion of two large randomized clinical trials, it will probably be added to the surgical armamentarium for the management of most breast cancers. Studies have been proposed or are under way to evaluate sentinel node mapping in head and neck cancer, penile and vulvar cancer, and gastrointestinal cancers.

Among the most exciting new anticancer products presented at the 2001 ASCO meeting were new drugs that block the epidermal growth factor receptor (EGFR). About 30% to 90% of carcinomas express high levels of EGFR. These include, among others, head and neck cancer, lung cancer, pancreatic cancer, colon cancer, breast cancer, ovarian cancer, and bladder cancer.

CHICAGO-Radio- and chemotherapy delivered concurrently produced greater overall and disease-free survival than radiotherapy alone in RTOG 9703, a phase II randomized trial of patients with advanced squamous cell carcinoma of the head and neck. The RTOG 9703 trial compared three treatment approaches using different chemotherapeutic agents, integration strategies, and timing sequences against the results of clinical studies involving radiotherapy alone.

CHICAGO-The degree of oxygenation of malignancies in the neck may indicate which patients with squamous cell carcinoma should receive adjuvant therapy, according to a study conducted at Duke University Medical Center.

LISBON, Portugal-For patients with locally advanced head and neck cancer, coupling cisplatin (Platinol) with radiotherapy leads to longer survival and fewer recurrences than does radiation alone, according to the first results of EORTC study 22931.

Fenretinide (N-4-hydroxyphenyl-retinamide, or 4-HPR) is a semisynthetic retinoid that was initially developed as a low-dose chemopreventative agent.[1-3] Unlike other naturally occurring retinoids such as all-trans, 13-cis, and 9-cis retinoic acids, fenretinide does not induce systemic catabolism that interferes with the maintenance of effective plasma levels during long-term use. This characteristic, combined with the agent’s low toxicity and its ability to block aspects of carcinogenesis, provided the rationale for the development of fenretinide in lower doses as a chemoprevention agent for breast, prostate, and bladder cancer.

ZUHL, Germany-Amifostine (Ethyol) used as cytoprotective therapy can reduce the occurrence of xerostomia, loss of taste, and fibrosis associated with radiochemotherapy for head and neck cancer. Jens Buentzel, MD, PhD, reported results of three studies at The First Investigators’ Congress on Radio-protection, held at the Kimmel Cancer Center at Jefferson University, Philadelphia. Dr. Buentzel is vice chairman of the Department of Otolaryngology, Head and Neck Oncology, Zentralklinikum Zuhl, Germany.

TORONTO, Canada-The combination of positron emission tomography (PET) and computed tomography (CT) has proved particularly advantageous in the diagnosis and treatment of cancer of the head and neck, Carolyn Cidis Meltzer, MD, said at the 48th Annual Meeting of the Society of Nuclear Medicine (abstract 133).

SAN FRANCISCO-Interim analysis of a clinical trial of patients with inoperable head and neck cancer (locally advanced or metastatic) showed superior response rates for the combination of cisplatin (Platinol), raltitrexed (Tomudex, investigational in the United States), levofolinic acid, and 5-fluorouracil (5-FU), compared with cisplatin, methotrexate, levofolinic acid, and 5-FU.

BETHESDA, Maryland-The FDA’s Oncologic Drugs Advisory Committee (ODAC) has voted not to recommend that the agency approve IntraDose (injectable cisplatin/epinephrine gel, Matrix Pharmaceuticals). Matrix is seeking to market the drug for the treatment of recurrent or refractory squamous cell carcinoma of the head and neck in patients not considered curable with surgery or radiotherapy.

A conventional course of radiation for squamous cell carcinoma in the United States is generally 70 Gy in 7 weeks, with a once-daily dose of 1.8 to 2 Gy. This schedule has a modest success rate in curing head and neck cancer. The

A conventional course of radiation for squamous cell carcinoma in the United States is generally 70 Gy in 7 weeks, with a once-daily dose of 1.8 to 2 Gy. This schedule has a modest success rate in curing head and neck cancer. The

Effective radiotherapy for patients with cancer should include maximal tumor cell killing with minimal injury to normal tissue. Radiation doses that can be delivered, without causing severe damage to surrounding normal