Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer in Complete Remission

A Phase III Trial Comparing High Versus Standard Dose of Prophylactic Cranial Irradiation (PCI) in Limited Small Cell Lung Cancer Complete Responders

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and prevent the spread of cancer to the brain. It is not yet known if standard-dose radiation therapy is more effective than high-dose radiation therapy in preventing the spread of limited-stage small cell lung cancer cells to the brain.

PURPOSE: This randomized phase III trial is comparing two different regimens of radiation therapy to see how well they work in treating patients with limited-stage small cell lung cancer in complete remission.

OBJECTIVES:

• Compare high-dose versus standard-dose prophylactic cranial radiotherapy in terms of the incidence of brain metastases and overall and disease free survival at 2 years in patients with limited stage small cell lung cancer in complete remission.
• Evaluate the quality of life and late sequelae in this patient population treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, age (60 and under vs over 60), and interval between the start of induction therapy and date of randomization (90 days or less vs 91-180 days vs more than 180 days). Patients are randomized into one of two treatment arms according to the prophylactic cranial radiotherapy dose.

• Arm I: Patients receive standard-dose prophylactic cranial radiotherapy (10 fractions/12 days).

• Arm II: Patients receive high-dose prophylactic cranial radiotherapy administered over 16 or 24 days based on the choice of their treatment center.

  • 18 fractions/24 days (conventional radiotherapy) OR
  • 24 fractions/16 days (accelerated hyperfractionated radiotherapy) Patients with isolated brain failure may undergo further radiotherapy.

Quality of life is assessed prior to randomization, at 6 months, at 1 year, and then annually thereafter.

Patients are followed at least every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 700 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically proven limited stage small cell lung cancer
• Complete response to induction therapy (at least on chest x-ray)
• Normal brain CT scan or MRI less than 1 month prior to study
• No metastases (including ipsilateral lung metastases and malignant pleural effusion)

PATIENT CHARACTERISTICS:

Age:

• 70 and under

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No prior cerebrovascular disease

Other:

• No epilepsy requiring permanent oral medication
• No other prior malignancy except skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy:

• Concurrent steroids allowed

Radiotherapy:

• Concurrent thoracic radiotherapy allowed

Surgery:

• Not specified

Other

• No other concurrent antitumoral agent