Interim analysis results did not meet criteria for second stage of trial

Recent progress in treatment of recurrent/metastatic SCCHN has been made with the introduction of the taxanes. Docetaxel as a single agent has a response rate of 22-42% and 17% in patients with recurrent disease. Capecitabine is an oral fluoropyrimidine prodrug that is converted into 5-FU. Previous studies have shown that the capecitabine/docetaxel combination has a synergistic inhibition of tumor growth, resulting in significantly superior efficacy in time to disease progression (TTP), overall survival, median survival and objective tumor response rate compared to docetaxel alone.

This trial will investigate the efficacy the combination of docetaxel and capecitabine in treating patients with recurrent/metastatic SCCHN.

OUTLINE: This is a multi-center study.

• Dexamethasone and antiemetic premedication1.
• Docetaxel: 60 mg/m2 for a 60 minute infusion day 1 of each cycle
• Capecitabine: 825 mg/m2 po BID Days 1-14

Repeat every 21 days until tumor progression or toxicity that requires discontinuation of therapy

Performance status: ECOG performance status 0 or 1

Life expectancy: At least 3 months

Hematopoietic:

• ANC of > 1,500/mm3
• Platelets > 100,000/mm3
• Hemoglobin > 8 gm/dl

Hepatic:

• Total Bilirubin £ ULN
• Albumin > 3
• Maximum Alk Phos > 2.5 x < 5 x ULN

Renal:

• Creatinine clearance of > 50 ml/ min (by Cockcroft-Gault)

Cardiovascular:

• No decompensated congestive heart failure or active angina.
• Clinically significant cardiac disease not well controlled with medication (eg. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction in the past 12 months is not allowed.

Pulmonary:

• Not specified

Inclusion Criteria:

• Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck.
• Recurrent/metastatic disease not amenable to surgery or salvage chemoradiation.
• Unidimensional measurable disease according to the RECIST
• In-field recurrence, within a prior radiation field only, distant metastatic disease
• Both in-field and metastatic sites of disease will require evaluation by a Radiation Oncologist to consider local radiation therapy first and will be eligible for possible enrollment one month after completion of the radiation therapy.
• Negative pregnancy test
• Patients may have received prior chemotherapy as part of chemoradiation or induction chemotherapy for initial treatment of disease confined to the head and neck region - Patients must have fully recovered from any prior radiation therapy

Exclusion Criteria:

• Patients who have relapsed < 6 months after completing a combined modality curative treatment that included a fluoropyrimidine or taxanes
• No brain metastases
• No major neurological disease, including stroke
• No prior chemotherapy regimen for recurrent/metastatic disease
• No prior history of capecitabine usage
• No prior history of docetaxel usage except in the induction setting for head and neck cancer which has been completed for greater than 6 months prior to beginning protocol therapy
• No past hypersensitivity to taxanes or 5 FU
• No hypersensitivity to docetaxel or other drugs formulated with polysorbate 80
• No current use of warfarin
• Patients must not be receiving ketoconazole, midazolam, erythromycin, orphenadrine, troleandomycin, cyclosporine or antiepileptics
• Patients must not be treated with any of the following on protocol therapy or within 28 days prior to beginning protocol therapy: sorivudine, brivudine, cimetidine, allopurinol
• Patients must have fully recovered from any prior surgery
• No known HIV seropositivity.
• No serious uncontrolled medical condition, uncontrolled peptic ulcer disease or malabsorption syndrome
• No peripheral neuropathy > grade 1
• Patients with a percutaneous gastrostomy (PEG) must be able take medications by tube.
• No daily consumption of alcohol
• No active infection
• No prior history of malignancy in the last 5 years, excluding in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin or Gleason Grade < VII organ confined prostate cancer.
• No current breastfeeding