Introduction: : Small cell lung cancer (SCLC) is initially a chemotherapy-sensitive disease. Nevertheless, drug-resistance results in disease recurrence in most patients. Many drugs, including antimetabolites, are active, but only minimal progress has been made in improving survival times for those with advanced disease. Based on the need to discover better systemic therapies, we conducted a phase II study of pemetrexed in patients with relapsed SCLC.
Patients and methods: : Eligible patients had SCLC or poorly differentiated neuroendocrine cancers of the lung, Eastern Cooperative Oncology Group performance status of 0 to 2, and had received less than or equal to two prior chemotherapy regimens (additional targeted agents were allowed). Both chemotherapy-sensitive (relapse >/=90 days from completion of first line therapy) and chemotherapy-resistant (progressive disease during or within 90 days from completion of first line treatment) patients were eligible and analyzed separately. Pemetrexed was administered at 500 mg/m intravenously every 21 days for up to six cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. The primary objective of the trial was to estimate the clinical benefit rate (complete plus partial response plus stable disease) in each group.
Results: : From January 2005 to September 2005, 20 patients were enrolled in the chemotherapy-sensitive arm and 23 patients in the chemotherapy-resistant arm. The majority of patients were men, the median age of the two groups were 62.5 and 65, respectively; 75% had a performance status of 0 or 1, and more than 50% had received more than one prior regimen. Grade 3/4 toxicities were as expected for pemetrexed. Progressive disease was the best response in 16 patients (80%) in the chemo-sensitive group and 19 patients (83%) in the chemo-refractory group. One patient had a partial response and three had stable disease in each group.
Conclusion: : Pemetrexed has minimal single agent activity in relapsed SCLC.