Chemotherapy Alone Not Recommended for Advanced Laryngeal or Hypopharyngeal Cancer

Is treatment with chemotherapy alone feasible for advanced laryngeal or hypopharyngeal squamous cell carcinoma?

Background: A favorable response to induction chemotherapy has been shown to be predictive of response to chemoradiation in patients with advanced laryngeal squamous cell cancer. Because of the adverse long-term sequelae of radiation therapy, including fibrosis and dysphagia, this study sought to determine if patients with advanced laryngeal cancer who had a favorable response to one cycle of induction chemotherapy could be successfully treated with subsequent chemotherapy alone.

Study design: Single arm phase II trial of patients with stage III or IVA laryngeal or hypopharyngeal cancer. All patients underwent induction chemotherapy with one cycle of cisplatin or carboplatin + 5-fluorouracil (5-FU). Patients with a complete clinical and histological response (measured by biopsy) after induction chemotherapy underwent subsequent treatment with chemotherapy alone, consisting of three additional alternating cycles of chemotherapy: cisplatin or carboplatin + 5-FU for cycles two and four, and weekly docetaxel for three weeks comprising the third cycle. Patients with a partial response to induction chemotherapy, defined as >50 percent reduction in primary tumor size, underwent concurrent chemoradiotherapy with cisplatin or carboplatin.

Nonresponders, defined as those with <50 percent reduction in primary tumor size after induction chemotherapy, were treated with laryngectomy and postoperative radiation. After definitive treatment, response to therapy was determined by exam under anesthesia eight weeks after the completion of definitive chemotherapy or chemoradiation. Complete responders received an additional two cycles of adjuvant chemotherapy with cisplatin or carboplatin + 5-FU.

Setting: University of Michigan

Synopsis: Thirty-two patients were enrolled between 2002-2004. Eleven patients (34 percent) had T4 tumors and 20 percent required pretreatment tracheostomy. Four patients (13 percent) had hypopharyngeal tumors. Only one patient (3 percent) had N3 disease; 10 patients (31 percent) had N0 disease.

Four patients (13 percent) had a complete response to induction chemotherapy and received chemotherapy alone, while four patients (13 percent) had less than a 50 percent response to induction chemotherapy and were treated with surgery and postoperative radiation therapy. None of the four patients treated with chemotherapy alone were disease-free at the completion of chemotherapy, and all four experienced failure in the neck. The three-year disease-specific survival was 78 percent; it was 25 percent in patients treated with chemotherapy alone and 100 percent in nonresponders to induction chemotherapy treated with surgery followed by radiation.

Bottom line: Organ preservation with chemotherapy alone is not feasible in patients with advanced laryngeal or hypopharyngeal cancer.