Preoperative Pemetrexed and Carboplatin for Select Stage IB, II, and III Non-Squamous Non-Small-Cell Lung Cancer

Inclusion criteria

• Histologically-confirmed NSCLC (adenocarcinoma, large cell, and undifferentiated). Patients with squamous histology are not eligible.
• Life expectancy of at least 12 weeks.
• Patients with the following stages of NSCLC:

• T2 N0 tumors: Limited to tumors >=4 cm.
• T1-2 N1 tumors.
• T3 N0-1 tumors (excluding superior sulcus tumors): Including tumors involving the chest wall, proximal airway, or mediastinal pleura where preoperative radiotherapy is not planned.
• T1-2 N2 tumors: For patients with N2 disease involving one zone (Upper zone (R), AP zone (L), subcarinal zone, or lower zone) and nodes <=2cm in diameter.
• T4 N0-1 tumors (excluding superior sulcus tumors): T4 lesions other than malignant effusions where radiotherapy is not planned.
• Patients with clinical N2 involvement must have histologic confirmation by mediastinoscopy (or alternate biopsy procedure).
• Tumors should be considered potentially resectable.
• No evidence of extrathoracic metastatic disease.
• Patients must have measurable disease by RECIST criteria.
• Patients must be candidates (medically) for chemotherapy followed by surgical resection.
• Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery; at least 3 weeks must have elapsed from the time of a major surgery.
• Laboratory values as follows:

• Absolute neutrophil count (ANC) >=1500/μL
• Hemoglobin (Hgb) >=10 g/dL
• Platelets >=100,000/uL
• AST/SGOT and ALT/SGPT within normal limits (WNL)
• Total bilirubin within normal limits (WNL)
• Calculated creatinine clearance >=45 mL/min
• ECOG Performance Status grade 0 or 1.
• The ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Alimta.
• The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
• Patient must be accessible for treatment and follow-up.
• Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion criteria

• Patients with the following stages are excluded:

• T1 N0;
• T2 N0, with primary tumor <4 cm;
• T1-2 N2, with multiple zones of N2 involvement;
• T3-4 N2;
• Any N3;
• Any TxNxM1 disease; or
• Any stage where surgery and/or chemoradiotherapy is the preferred initial approach in management, as deemed by the treating physician.
• Squamous or predominant squamous mixed histologies.
• Mixed small-cell and non-small cell histologies.
• Pulmonary carcinoid tumors.
• Presence of third space fluid which cannot be controlled by drainage.
• Use of erythropoietin as a hematopoietic growth factor is not allowed.
• Cardiac disease, including: congestive heart failure (CHF) > Class II per New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Women who are pregnant (positive pregnancy test) or lactating.
• Use of any non-approved or investigational agent within 30 days of administration of the first dose of study drug.
• Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
• Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
• History of hypersensitivity to active or inactive excipients of any component of treatment.
• Inability to comply with study and/or follow-up procedures.