We present the rationale and study design of the phase I and II trials of carboplatin plus pemetrexed followed by pemetrexed, which the multicenter trial on safety and efficacy of first-line therapies in elderly (75 years old or more) advanced non-small-cell lung cancer (NSCLC) patients. Treatment consists of up to four cycles of induction therapy followed by maintenance therapy until disease progression or treatment discontinuation in 3–6 patients/cohort (Phase I), and 34 patients (phase II). The primary end points of the present study are to determine the recommended dose (RD) and maximum tolerance dose (MTD) of carboplatin plus pemetrexed in phase I, and, in phase II, the efficacy objectives are to assess the 1-year survival rate, the overall survival (OS), response rates, progression-free survival (PFS). In addition, safety will be investigated in phase II study. If the primary objective (recommended dose and 1-year survival rate) is achieved, this study will provide robust results on an alternative treatment option, carboplatin plus pemetrexed followed by maintenance therapy with pemetrexed, for patients with elderly (75 years old or more) advanced nonsquamous NSCLC.