RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have advanced mouth cancer.

Condition	Treatment or Intervention	Phase
lip and oral cavity cancer Oropharyngeal Cancer Head and Neck Cancer	Drug: ethynyluracil  Drug: fluorouracil  Drug: hydroxyurea	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Assess the feasibility of the administration of ethynyluracil concurrently with fluorouracil and radiotherapy in patients with advanced oral cancer.

II. Determine the maximum tolerated dose (MTD) and dose-limiting toxicities of this regimen in this patient population.

PROTOCOL OUTLINE: This is a dose escalation study of fluorouracil and hydroxyurea.

Patients receive oral ethynyluracil every 12 hours on days 1-7 and oral fluorouracil every 12 hours on days 2-6. Radiotherapy to the head and neck is administered twice daily on days 2-6. Treatment continues for 5-7 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities.

Once the MTD of fluorouracil is determined, hydroxyurea is added to the treatment regimen. Patients receive fluorouracil and ethynyluracil as per the treatment schedule outlined above. Patients also receive oral hydroxyurea every 12 hours for 11 doses on days 1-6. Radiotherapy is administered as above.

Cohorts of 3-6 patients receive escalating doses of hydroxyurea until the MTD is determined.

Once the MTD of fluorouracil and hydroxyurea are determined, an additional 10 patients receive Phase II doses of ethynyluracil, fluorouracil and hydroxyurea as per the treatment schedule outlined above. Treatment continues in the absence of unacceptable toxicity.

Patients are followed at 4-6 weeks, then every 6 months until death.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study over 2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed advanced malignant oral or laryngeal neoplasm requiring regional radiotherapy and not amenable to standard therapy
• Tumor site amenable to radiotherapy

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: Recovered from prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: Recovered from prior radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Expected 2 year survival less than 10% in previously untreated patients
• Hematopoietic: WBC at least 3,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Not specified
• Renal: Creatinine clearance at least 50 mL/min
• Other: No severe infection or medical illness that would preclude study; Must be able to swallow and retain oral medications; Not pregnant

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States

Study chairs or principal investigators

Everett E. Vokes,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000067580; NU-V95N4; NCI-G00-1680
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004901
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08