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. It is not yet known if radiation therapy plus chemotherapy is more effective than radiation therapy alone in treating patients with advanced head and neck cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without chemotherapy in treating patients with advanced head and neck cancer.

Condition	Treatment or Intervention	Phase
Oropharyngeal Cancer Head and Neck Cancer lip and oral cavity cancer	Drug: bleomycin  Drug: fluorouracil  Drug: leucovorin calcium  Drug: methotrexate  Drug: vincristine	Phase III

Further Study Details: 

OBJECTIVES: I. Determine whether the addition of methotrexate (MTX) or VBMF (vincristine/bleomycin/methotrexate/fluorouracil) to radiotherapy for advanced carcinoma of the head and neck (with or without primary surgery) influences locoregional control and prolongs survival.

II. Determine whether an effect on locoregional control or survival is apparent when chemotherapy is given during or following radiotherapy and whether it is increased when chemotherapy is given at both times.

III. Determine, in a special randomization of patients with cancer of the oral cavity or oropharynx, whether neck irradiation improves locoregional control and survival.

PROTOCOL OUTLINE: Randomized study. Patients without prior surgery are randomized 1:2 to Arms I:II-IV, while those with prior surgery are randomized 1:1 between Arms I and II only. Patients with tumors of the oral cavity or oropharynx may elect additional randomization between Arms V and VI and will receive irradiation of the primary according to the Manchester regimen.

Arm I: Radiotherapy. Irradiation of the primary and/or lymph nodes according to 1 of 2 regimens (Manchester 3-week schedule or SECOG 6-week schedule) using megavoltage equipment.

Arm II: Radiotherapy plus Concurrent Single-agent or 4-Drug Combination Chemotherapy with Leucovorin Rescue. Involved-field irradiation as in Arm I; plus Methotrexate, MTX, NSC-740; with Leucovorin calcium, CF, NSC-3590; or VBMF: Vincristine, VCR, NSC-67574; Bleomycin, BLEO, NSC-125066; MTX; Fluorouracil, 5-FU, NSC-19893; with CF.

Arm III: Radiotherapy plus Subsequent Single-agent or 4-Drug Combination Chemotherapy with Leucovorin Rescue. Involved-field irradiation as in Arm I; plus MTX or VBMF; with CF.

Arm IV: Radiotherapy plus Concurrent and Subsequent Single-agent or 4-Drug Combination Chemotherapy with Leucovorin Rescue. Involved-field irradiation as in Arm I; plus MTX or VBMF; with CF.

Arm V: Radiotherapy. Neck node irradiation using megavoltage equipment.

Arm VI: Observation. No nodal irradiation.

PROJECTED ACCRUAL: At least 1,000 patients will be entered.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed squamous cell cancer of the head and neck suitable for treatment with radiotherapy
• T2, T3, or T4 primary lesions; Any N; No distant metastasis
• May also be anaplastic carcinoma, verrucous carcinoma, or transitional cell carcinoma (as of 1/97)
• No occult primaries (as of 1/97)
• No adenocarcinomas, lymphomas, or melanomas (as of 1/97)
• Synchronous head and neck tumors are eligible (tumor with the worse prognosis is entered into study) (as of 1/97)
• Patients receiving surgery to neck nodes only must be randomized as surgery patients (as of 1/97)
• Patients with tumors of the oral cavity or oropharynx may additionally elect randomization to nodal irradiation vs. no further therapy provided there is no second primary

--Prior/Concurrent Therapy--

• Biologic therapy: No prior therapy
• Chemotherapy: No prior therapy
• Endocrine therapy: No prior therapy
• Radiotherapy: No prior therapy
• Surgery: Prior biopsy or excision allowed

--Patient Characteristics--

• Age: 75 and under for patients electing participation in the nodal vs. no nodal irradiation portion of the study
• Performance status: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Other: Fit for any protocol treatment option; Willing to receive any protocol treatment option; Prior malignancy allowed provided the treating clinician considers the patient cured

India
      Raj Tilak, Indore,  452001,  India
United Kingdom, England
      Derriford Hospital, Plymouth,  England,  PL6 8DH,  United Kingdom
      Middlesex Hospital- Meyerstein Institute, London,  England,  W1N 8AA,  United Kingdom
      Royal Sussex County Hospital, Brighton,  England,  BN2 5BE,  United Kingdom
      Southend General Hospital, Westcliff-On-Sea,  England,  United Kingdom
United Kingdom, Northern Ireland
      Belfast City Hospital Trust, Belfast,  Northern Ireland,  BT8 8JR,  United Kingdom
      Royal Victoria Hospital, Belfast,  Northern Ireland,  BT12 6BJ,  United Kingdom

Study chairs or principal investigators

Jeffrey S. Tobias,  Study Chair,  Cancer Research Campaign Clinical Trials Centre   

Study ID Numbers:  CDR0000076951; CRC-PHASE-III-91001; UKHAN-1
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002476
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08