Head & Neck Cancer

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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.

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.

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

ZUHL, Germany-Amifostine (Ethyol) used as cytoprotective therapy can reduce the occurrence of xero-stomia, loss of taste, and fibrosis associated with radiochemotherapy for head and neck cancer. Results of three studies were reported by Jens Buentzel, MD, PhD, vice chairman of the Department of Otolaryngology, Head and Neck Oncology, Zentralklinikum Zuhl, Germany.

ST. LOUIS-To determine whether cytoprotective amifostine (Ethyol) can reduce the incidence of hypothyroidism in patients with head and neck cancer treated with radiotherapy, a trial is set to begin at Washington University in St. Louis. The proposed trial is currently undergoing institutional review board (IRB) consideration and has not yet enrolled patients.

PHILADELPHIA-For head and neck cancer patients, subcutaneous (SC) amifostine (Ethyol) provides equal protection against radiation-induced grade 2 acute xerostomia compared to intravenous (IV) amifostine, Pramila Rani Anné, MD, reported. She cautioned, however, that SC amifostine should be used only in clinical trials until ways to prevent cutaneous toxicities are worked out.

ST. LOUIS-Intensity modulated radiation therapy (IMRT) and use of radioprotectant agents may help reduce late-appearing radiation side effects, reported K. S. Clifford Chao, MD. Dr. Chao is associated radiation oncologist, Department of Radiation Oncology at the Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis.