RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of radiation therapy plus fludarabine in treating patients who have locally advanced cancer of the mouth, pharynx, or larynx.

Condition	Treatment or Intervention	Phase
stage IV squamous cell carcinoma of the lip and oral cavity stage IVA squamous cell carcinoma of the nasopharynx stage III squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx stage III squamous cell carcinoma of the lip and oral cavity stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx stage IVB squamous cell carcinoma of the nasopharynx stage III squamous cell carcinoma of the nasopharynx stage IV squamous cell carcinoma of the hypopharynx	Drug: fludarabine	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of fludarabine that can be given during the sixth and seventh weeks of radiotherapy in patients with locally advanced squamous cell carcinoma of the oral cavity, pharynx, or larynx, based on the systemic toxicity of the drug and the acute mucosal reactions in the irradiated fields. II. Document the qualitative and quantitative toxicity of this combination therapy in this patient population.

PROTOCOL OUTLINE: This is a dose escalation study of fludarabine. Patients receive radiotherapy on days 1-5 for 7 weeks. Patients receive fludarabine IV on days 1-5 of weeks 6 and 7 of radiotherapy. Fludarabine is administered 3-4 hours prior to daily radiotherapy. Cohorts of 3 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose that produces a severe toxicity rate nearest to 20%. Patients are followed every 4 weeks after the completion of treatment until acute reactions have resolved, then every 3 months for 2 years, every 4 months for 1 year, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for this study within 1.5 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed squamous cell carcinoma of the oral cavity, pharynx, or larynx for which surgery would result in significant functional impairment; Stage III or IV (T3-4 or N2-3)
• No distant metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy
• Surgery: See Disease Characteristics

--Patient Characteristics--

• Age: 18 and over
• Performance status: Zubrod 0-2
• Life expectancy: At least 6 months
• Hematopoietic: Granulocyte count at least 1,500/mm3; Platelet count at least 150,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; SGOT less than 4 times upper limit of normal; PT/PTT normal
• Renal: Creatinine no greater than 1.5 mg/dL
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; No other concurrent acute illness or infection

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States

Study chairs or principal investigators

K. Kian Ang,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000067492; MDA-ID-95038; NCI-H99-0046
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004246
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08