Trial Information

Multimodality Management of Head and Neck Cancer: A Phase II Trial of Induction Chemotherapy, Organ Preservation Surgery, and Concurrent Chemoradiotherapy

OBJECTIVES:

Primary

- To assess the complete and overall response rate of neoadjuvant docetaxel, cisplatin,
fluorouracil, and leucovorin calcium in previously untreated patients with local
regionally advanced head and neck cancer.

- To evaluate the feasibility of a multimodality treatment approach with the goal of
reducing long-term sequelae.

- To evaluate prospectively, the impact of neoadjuvant chemotherapy, concurrent
chemoradiotherapy, and organ preservation surgery on overall survival, time to
progression, and pattern of disease recurrence in these patients.

- To evaluate prospectively, biochemical correlates of response and prognosis, including
markers such as thymidylate synthetase, ribonucleotide reductase, and ERCC1 (measured
by quantitative PCR), p53 (evaluated by IHC), and HPV status and apoptosis (TUNEL
assay).

Secondary

- To evaluate treatment-associated morbidity with the use of a quality of life assessment
tool.

- To compare the results of diagnostic salivary cytology with those of histopathology at
initial diagnosis as well as follow-up in head and neck cancer patients.

- To evaluate the tolerability of combined chemoradiotherapy using gemcitabine and
cisplatin after definitive surgery for squamous cell carcinoma of the head and neck.

OUTLINE: Patients receive neoadjuvant induction chemotherapy comprising docetaxel IV over 1
hour on day 1 and cisplatin IV, leucovorin IV, and fluorouracil IV over 24 hours on days
1-4. Induction chemotherapy repeats every 28 days for 3 courses in the absence of disease
progression or unacceptable toxicity.

Patients with partial response at the primary site may undergo radical or functional
resection of the primary tumor within 3 weeks of completion of neoadjuvant therapy.

Beginning within 4 weeks of completion of neoadjuvant therapy, patients with persistent
disease or complete response after chemotherapy at the primary or neck then undergo
radiotherapy 5 days a week for 7 weeks and receive gemcitabine hydrochloride IV over 30
minutes and cisplatin IV over 60 minutes on day 1 of each week of radiotherapy in the
absence of disease progression or unacceptable toxicity.

Patients complete the FACT-H&N quality of life questionnaire at baseline and at completion
of neoadjuvant therapy.

Tissue biopsies are collected at baseline, periodically during therapy, at surgery, and
after radiotherapy. Tissue is examined for gene and protein expression.