Tipifarnib Plus Radiation Therapy After Combination Chemotherapy in Treating Patients With Stage III Non-Small Cell Lung Cancer

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of tipifarnib given concurrently with radiotherapy after induction chemotherapy comprising paclitaxel and carboplatin and followed by maintenance therapy with tipifarnib in patients with stage IIIA or IIIB non-small cell lung cancer.
• Determine the tumor response at 3 months in patients treated with this regimen.

OUTLINE: This is multicenter, dose-escalation study of tipifarnib.

Patients receive induction chemotherapy comprising carboplatin IV over 30 minutes on day 1 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses.

Beginning 4-6 weeks after the completion of induction chemotherapy, patients receive oral tipifarnib twice daily for 7 weeks. Patients undergo radiotherapy once daily 5 days a week for 7 weeks beginning 3 days after the start of tipifarnib. After completion of radiotherapy, patients receive oral tipifarnib twice daily for 4 days and then once daily for 4 days.

Cohorts of 3-6 patients receive escalating doses of tipifarnib while receiving radiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Beginning 4-6 weeks after the completion of radiotherapy and tipifarnib, patients receive maintenance therapy comprising oral tipifarnib twice daily on days 1-21. Maintenance therapy repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3, 6, and 12 months.

PROJECTED ACCRUAL: Approximately 9-12 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer

• Locally advanced (stage IIIA or IIIB) disease requiring radiotherapy
• No malignant pleural effusion

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• No grade 2 or greater elevation of liver function tests

Renal:

• Creatinine no greater than 1.5 times normal

Pulmonary:

• FEV_1 at least 600 cc

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No grade 3 or 4 peripheral neuropathy
• No known allergy to imidazole drugs (e.g., ketoconazole, miconazole, econazole, or terconazole)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Up to 2 prior or concurrent carboplatin and paclitaxel chemotherapy regimens allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior thoracic radiotherapy

Surgery:

• At least 3 weeks since prior exploratory thoracotomy