chemotherapy combined with radiation therapy in treating patients with limited-stage small cell lung cancer

Conditions: Lung Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. combining chemotherapy with radiation therapy may kill more tumor cells. purpose: phase i trial to study the effect on the body when combining irinotecan and cisplatin with radiation therapy in treating patients who have limited-stage small cell lung cancer that could not be completely removed during surgery.

objectives: * determine the maximum tolerated dose of irinotecan administered with cisplatin and thoracic radiotherapy (given at two different schedules) in patients with limited stage small cell lung cancer. * determine the qualitative and quantitative toxicity and non-dose-limiting toxicity of these regimens in these patients. * determine the reversibility of all toxic effects associated with these regimens in these patients. outline: this is a non-randomized, dose-escalation study of irinotecan. patients are assigned to 1 of 2 radiotherapy (rt) treatment groups. * radiotherapy: * group i: patients undergo thoracic rt twice daily, 5 days a week, for 3 weeks. * group ii: patients undergo thoracic rt once daily, 5 days a week, for 7 weeks. * concurrent chemotherapy: patients receive irinotecan iv over 60-90 minutes on days 1 and 8 and cisplatin iv over 1 hour on day 1. treatment repeats every 3 weeks for 1 course for group i and 2 courses for group ii. * post rt chemotherapy: patients receive irinotecan and cisplatin as above for 3 courses for group i and 2 courses, beginning after rt is complete, for group ii. sequential cohorts of 6 patients per group receive escalating doses of irinotecan until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. patients are followed every 3 months for 1 year and then 6 months for 4 years. projected accrual: a total of 12-36 patients (6-18 per group) will be accrued for this study within 18 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed small cell lung cancer by one of two methods: * fine needle aspiration biopsy * two positive sputa * must have limited disease as defined by all of the following: * stage i-iiib * confined to 1 hemithorax * no t4 tumor based on malignant pleural or pericardial effusion * patients with pleural effusion too small to tap under ct guidance and not evident on chest x-ray are allowed * no n3 disease based on contralateral hilar or contralateral supraclavicular involvement * measurable or evaluable disease * tumor must be able to be encompassed by specified radiotherapy fields without unacceptable risk of serious pulmonary compromise * no complete tumor resection * no pericardial effusion (regardless of cytology) patient characteristics: age * 18 and over performance status * zubrod 0-1 life expectancy * not specified hematopoietic * absolute granulocyte count at least 1,500/mm\^3 * platelet count at least 120,000/mm\^3 hepatic * bilirubin no greater than 1.5 mg/dl * no known gilbert's disease renal * creatinine no greater than 1.5 mg/dl cardiovascular * no myocardial infarction within the past 6 months * no symptomatic heart disease pulmonary * forced expiratory volume (fev)_1 at least 1.0 l/sec * no uncontrolled bronchospasms * no uncompensated chronic obstructive pulmonary disease other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no pre-existing peripheral neuropathy grade 2 or greater * no other malignancy within the past 2 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the bladder or cervix * no other concurrent serious medical illness prior concurrent therapy: biologic therapy * no prior biologic therapy chemotherapy * no prior chemotherapy endocrine therapy * not specified radiotherapy * no prior radiotherapy * no concurrent intensity-modulated radiotherapy surgery * see disease characteristics other * at least 7 days since prior enzyme-inducing anti-convulsant drugs (eiacds) (e.g., phenytoin, carbamazepine, or phenobarbital) if used on a regular basis for more than 2 weeks * less than 2 weeks of regular use of eiacds does not require a 7-day wash-out period * at least 14 days since prior hypericum perforatum (st. john's wort) * no concurrent eiacds * no concurrent amifostine during chemoradiotherapy * concurrent gabapentin or other non-eiacds allowed

Keywords: limited stage small cell lung cancer