Title
Surgery and Radiation Therapy With or Without Interleukin-2 in Treating Patients With Cancer of the Mouth or Oropharynx
Multicentre Randomised Trial of Inductive and Adjuvant Perilymphatically Injected Proleukin (rlL-2) in The Treatment of Operable Primary Squamous Cell Carcinoma of The Oral Cavity and Oropharynx
Phase
Phase 3Lead Sponsor
University of MilanStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Head and Neck CancerIntervention/Treatment
aldesleukin ...Study Participants
260RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill cancer cells of the mouth or oropharynx. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not known whether giving interleukin-2 with surgery and radiation therapy is more effective than surgery and radiation therapy alone.
PURPOSE: This randomized phase III trial is studying surgery and radiation therapy alone to see how well they work compared to surgery, radiation therapy, and interleukin-2 in treating patients with cancer of the mouth or oropharynx.
OBJECTIVES:
Compare the disease-free and overall survival in patients with previously untreated squamous cell carcinoma of the oral cavity or oropharynx treated with resection with or without and neoadjuvant and adjuvant perilymphatic interleukin-2 (IL-2) and radiotherapy.
Compare the response rate in patients treated with these regimens.
Determine the local and systemic effects of locoregional IL-2 on host-tumor interaction and immune properties in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and tumor stage (T2, N0-2 vs T2, N3 or T3-4, N0-3). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients undergo induction comprising interleukin-2 (IL-2) via perilymphatic injections to the ipsilateral myelohyoid muscle and insertion of the sternocleidomastoid muscle on days 1-5 and 8-12. Within 10 days after the last IL-2 injection, patients undergo en bloc resection of the primary tumor and corresponding lymphatic drainage area and pre-study margins. Beginning within 4 weeks after surgery, patients with T2, N0-3 disease but with pathohistological evidence of node invasion or capsular rupture of node metastasis or T3-4, N0-3 disease undergo adjuvant radiotherapy 5 days a week for 4.5-6.5 weeks. Beginning within 4 weeks after surgery or radiotherapy (if applicable), patients receive adjuvant IL-2 via perilymphatic injections to the contralateral myelohyoid muscle and insertion of the sternocleidomastoid muscle on days 1-5. Adjuvant IL-2 continues monthly for at least 1 year in the absence of disease progression.
Arm II: Patients undergo resection and radiotherapy (if eligible) as in arm I. Patients are followed monthly for 1 year and then every 2 months for 2 years.
PROJECTED ACCRUAL: A total of 260 patients (130 per treatment arm) will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically proven squamous cell carcinoma of the oral cavity or oropharynx Operable, primary, unilateral, stage T2-4, N0-3, M0 disease No high probability of bilateral lymphatic spread (requirement for bilateral neck dissection) No tumor involvement of the following sites: Pterygopalatine fossa Carotid artery Maxillary sinus Facial skin Anterior floor of the mouth Base of the tongue infiltrating more than 1 cm Measurable or evaluable disease by physical exam and/or noninvasive imaging PATIENT CHARACTERISTICS: Age: 75 and under Performance status: ECOG 0-2 OR Karnofsky 70-100% Life expectancy: More than 3 months Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 60,000/mm3 Hematocrit at least 30% Hepatic: Bilirubin normal Hepatitis B surface antigen negative Renal: Creatinine normal Cardiovascular: No congestive heart failure No uncontrolled hypertension No coronary artery disease No serious arrhythmia No evidence of prior myocardial infarction on ECG (stress test required if in doubt) Other: HIV negative No autoimmune disease No contraindications to pressor agents No serious infection requiring antibiotics No other concurrent primary malignancy Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: No prior or other concurrent immunotherapy Chemotherapy: No prior or concurrent chemotherapy Endocrine therapy: No prior or concurrent hormonal therapy No concurrent corticosteroids Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics No prior major organ allografts Other: No other prior therapy No other concurrent investigational drugs, agents, or devices No concurrent nonsteroidal antiinflammatory drugs, ranitidine, cimetidine, or coumarin
