RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth and by making tumor cells more sensitive to radiation therapy.
Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy,
such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells
either by killing the cells or by stopping them from dividing and may also make tumor cells
more sensitive to radiation therapy.
PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when
given together with radiation therapy after combination chemotherapy in treating patients
with stage III non-small cell lung cancer.
- 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
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
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.
- Histologically confirmed non-small cell lung cancer
- Locally advanced (stage IIIA or IIIB) disease requiring radiotherapy
- No malignant pleural effusion
- 18 and over
- ECOG 0-2
- Not specified
- WBC at least 3,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 1.5 mg/dL
- No grade 2 or greater elevation of liver function tests
- Creatinine no greater than 1.5 times normal
- FEV_1 at least 600 cc
- 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
PRIOR CONCURRENT THERAPY:
- Not specified
- Up to 2 prior or concurrent carboplatin and paclitaxel chemotherapy regimens allowed
- Not specified
- See Disease Characteristics
- No prior thoracic radiotherapy
- At least 3 weeks since prior exploratory thoracotomy