Bortezomib and Pemetrexed Disodium in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors

OBJECTIVES: Primary * Determine the safety, including dose-limiting toxicities, and feasibility of combining bortezomib with pemetrexed disodium in patients with advanced non-small cell lung cancer (NSCLC) or other solid tumors. (Phase I) * Determine the response rate in patients with advanced NSCLC treated with this regimen. (Phase II) Secondary * Compare the toxicity of 2 different schedules of bortezomib and pemetrexed disodium in patients with advanced solid tumors. (Phase I) * Determine the maximum tolerated dose (MTD) of bortezomib when administered with pemetrexed disodium in 2 different treatment schedules in these patients. (Phase I) * Determine, preliminarily, the efficacy of the combination of bortezomib and pemetrexed disodium in patients with advanced solid tumors. (Phase I) * Assess the overall survival and progression-free survival of these patients. (Phase II) * Evaluate the frequency and severity of toxicities associated with this regimen. (Phase II) Tertiary * Perform laboratory correlative studies on tumor tissue and blood samples to investigate potential predictors of response. (Phase II) OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II, open-label study. * Phase I: Patients will be accrued, in an alternating fashion, to 1 of 2 treatment groups. * Group I: Patients receive pemetrexed disodium IV on day 1 and bortezomib IV on days 1, 4, 8, and 11. * Group II: Patients receive pemetrexed disodium IV on day 1 and bortezomib IV on days 1 and 8. In both groups, treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients per group receive escalating doses of bortezomib 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. * Phase II: Patients receive pemetrexed disodium bortezomib (at the MTD) as in either group I or group II of the phase I portion of the study. Selection of the treatment schedule is based upon observed toxicity, safety, tolerability, efficacy, and clinical practicality. Blood is drawn at baseline and prior to courses 2 and 3 for correlative and molecular studies. Tumor tissue and blood samples from patients enrolled in the phase II portion of the study are examined for various biological markers. Immunohistochemistry is used to measure BCL-2 gene, BCL-xL gene, BAX gene, and p27. Reverse transcriptase-polymerase chain reaction is used to assay the expression of thymidylate synthase, folsyl-polyglutamate synthase, and reduced folate carrier. Levels of plasminogen-activator inhibitor 1 gene, vascular endothelial growth factor, and osteopontin are measured by immunoenzyme techniques. The nuclear expression of NF-kB and p27 in blood is compared before and after study treatment by flow cytometry. After completion of study treatment, patients in phase I are followed for 30 days and patients in phase II are followed periodically.