chemotherapy, tirapazamine, and radiation therapy in treating patients with non-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. tirapazamine may make the tumor cells more sensitive to radiation therapy. combining chemotherapy, radiation therapy, and tirapazamine may kill more tumor cells. purpose: phase i trial to study the effectiveness of combining chemotherapy with tirapazamine and radiation therapy in treating patients who have stage ii or stage iii non-small cell lung cancer.

objectives: * determine the maximum tolerated dose of tirapazamine when administered with paclitaxel, carboplatin, and concurrent radiotherapy in patients with stage iib-iiib non-small cell lung cancer. * determine, preliminarily, the response rate and survival of patients treated with this regimen. * determine the toxicity of this regimen in these patients. outline: this is a multicenter, dose-escalation study of tirapazamine. patients receive induction chemotherapy comprising tirapazamine iv over 2 hours and carboplatin iv over 30 minutes on days 1, 8, 15, 22, 29, and 36 and paclitaxel iv over 1 hour on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39. beginning on day 1, patients undergo radiotherapy once daily 5 days a week for 6.5 weeks. beginning 4-5 weeks after completion of radiotherapy, patients with stable or responding disease receive consolidation chemotherapy comprising paclitaxel iv over 3 hours and carboplatin iv over 30 minutes on days 1 and 22. cohorts of 3-6 patients receive escalating doses of tirapazamine until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed every 3 months. projected accrual: approximately 3-30 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed primary bronchogenic non-small cell lung cancer * adenocarcinoma * large cell carcinoma * squamous cell carcinoma * stage iiia or iiib disease (t1-4, n2-3) * mediastinal lymph nodes at least 2 cm in diameter by radiography sufficient to stage n2-3 (must be node positive \[cytologically or histologically confirmed\] if largest mediastinal node is less than 2 cm in diameter) or * selected stage iib disease (t3, n0 or t3, n1 with a medical condition that precludes surgery) * no malignant pleural effusion * measurable or evaluable disease by chest x-ray or ct scan * no metastatic disease patient characteristics: age: * 18 and over performance status: * zubrod 0-2 or * ecog 0-2 life expectancy: * not specified hematopoietic: * wbc at least 3,500/mm\^3 * platelet count normal hepatic: * not specified renal: * creatinine clearance at least 60 ml/min cardiovascular: * no uncontrolled congestive heart failure * no unstable angina * no unstable cardiac arrhythmias pulmonary: * fev_1 at least 1.0 l other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no clinically significant hearing loss prior concurrent therapy: biologic therapy: * not specified chemotherapy: * no prior chemotherapy for lung cancer endocrine therapy: * not specified radiotherapy: * no prior radiotherapy for lung cancer surgery: * see disease characteristics

Keywords: stage ii non-small cell lung cancer squamous cell lung cancer large cell lung cancer stage iiia non-small cell lung cancer stage iiib non-small cell lung cancer adenocarcinoma of the lung