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 chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have advanced and/or recurrent head and neck cancer.

Condition	Treatment or Intervention	Phase
lip and oral cavity cancer Head and Neck Cancer Oropharyngeal Cancer	Drug: fluorouracil  Drug: gemcitabine  Drug: paclitaxel	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine when administered with paclitaxel and fluorouracil with concurrent hyperfractionated radiotherapy in patients with advanced and/or recurrent head and neck cancer. II. Determine the MTD and DLT of gemcitabine as a single agent with radiotherapy in these patients. III. Determine the efficacy of concurrent chemoradiotherapy in terms of time to progression, pattern of failure, and overall survival in patients with measurable disease. IV. Determine gemcitabine and fluorouracil pharmacokinetics in these patients.

PROTOCOL OUTLINE: This is a dose escalation study of gemcitabine, conducted in two phases. Phase A: Patients receive fluorouracil IV continuously on days 1-5, paclitaxel IV over 1 hour on day 2, and radiotherapy administered twice daily on days 1-5. This regimen is repeated every 2 weeks for 2 courses, then gemcitabine IV over 30 minutes is added on day 2 after paclitaxel. This regimen is administered every 2 weeks for 3 courses. Patients with responsive disease may continue chemotherapy (without radiotherapy) for 2 courses beyond maximum response. Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity. Phase B: After the MTD of gemcitabine is determined in phase A, further dose escalation of gemcitabine may be performed with concurrent radiotherapy (without fluorouracil or paclitaxel). The MTD is determined as in phase A. Patients are followed monthly for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 30-40 patients will be accrued for this study within approximately 2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically proven head and neck cancer requiring regional radiotherapy; Locoregional, recurrent disease after primary therapy with surgery, radiation, or both OR Stage IV, no prior therapy, and not amenable to conventional therapy with curative intent
• Metastatic disease allowed if predominant site and associated symptoms require local treatment in the head and neck region

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: Recovered from any prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; Recovered from any prior radiotherapy
• Surgery: See Disease Characteristics; Recovered from any prior surgery

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: Not specified
• Hematopoietic: WBC greater than 3,000/mm3; Absolute neutrophil count greater than 1,500/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; Transaminases no greater than 2.5 times upper limit of normal
• Renal: Creatinine no greater than 2.0 mg/dL
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; No significant infection; No other severe medical illness

Illinois
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States

Study chairs or principal investigators

Athanassios Argiris,  Study Chair,  Robert H. Lurie Cancer Center   

Study ID Numbers:  CDR0000067313; NU-C97N2; NCI-G99-1590
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  December 10, 1999
ClinicalTrials.gov Identifier:  NCT00004097
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08