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Summary: Carcinomatous meningitis (CM) and spinal cord metastases (SCM) are uncommon, yet fatal complication for patients with non-small cell lung cancer (NSCLC). Gefitinib, developed to inhibit the tyrosine kinase of the epidermal growth factor receptor (EGFR), represents the first new treatment modality for NSCLC to emerge from the last decade. Furthermore, it is an attractive option for lung cancer patients with CNS metastasis because of its mild toxicity profile, but there are not much data on the ability of gefitinib to cross the blood–brain barrier. And also, the response of patients with CM and SCM to gefitinib has rarely been reported on. We report here a good response to gefitinib by a heavily pretreated 59-year-old man with CM and SCM. [Copyright &y& Elsevier]

• Olmutinib showed effective clinical activity. • The safety profile of olmutinib was manageable. • Olmutinib showed potential in T790M-positive NSCLC after failing ≥1 prior EGFR-TKI. The aim of this phase 1/2 study was to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of olmutinib in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who had failed ≥ 1 previous line of EGFR-tyrosine kinase inhibitor (TKI) therapy. Phase 1 consisted of dose-escalation and four dose-expansion parts (1: olmutinib 300 mg once daily; 2A: 800 mg once daily [ EGFR T790 M mutation-positive patients]; 2B: 500 mg twice daily [ EGFR T790 M mutation-positive]; 3: 800 mg once daily [ EGFR T790 M mutation-negative]). In phase 2, EGFR T790 M mutation-positive patients received olmutinib 800 mg once daily. Data from expansion part 2A and phase 2 were integrated ('pooled phase 2′). Each olmutinib cycle was 21 days. Outcomes included: tumor response, treatment-emergent adverse events (TEAEs), pharmacokinetic parameters. Overall, 272 patients received at least one olmutinib dose: dose-escalation (n = 66), expansion parts (n = 165), phase 2 (n = 41). In pooled phase 2, the overall objective response rate, confirmed by independent review, was 55.1% (38/69 evaluable patients; 95% CI, 42.6–67.1). All responses were partial responses; 23 patients had stable disease. Estimated median progression-free survival was 6.9 (95% CI, 5.6–9.7) months; estimated median overall survival was not reached. The most frequent treatment-related AEs were diarrhea (59.2% of patients), pruritus (42.1%), rash (40.8%), and nausea (39.5%). Olmutinib showed effective clinical activity with a manageable safety profile, indicating therapeutic potential for T790M-positive NSCLC patients who have failed ≥ 1 previous line of EGFR-TKI therapy. [ABSTRACT FROM AUTHOR]

Abstract: Objective This prospective multicenter study conducted by the Korean Cancer Study Group evaluated the efficacy and safety of pemetrexed in Korean patients with advanced non-small cell lung cancer (NSCLC) who had prior chemotherapy. Patients and methods: Patients with stage IIIB or IV NSCLC in whom prior chemotherapy failed received pemetrexed 500mg/m2 every 3 weeks with folic acid and vitamin B12 supplementation until disease progression or the development of intolerable toxicity. Eighty-one patients were enrolled. Results The overall response rate for 78 evaluable patients was 5.1% [95% confidence interval (CI) 1.4–12.6; partial response 4/78, no complete response]. The disease control rate including complete, partial response and stable disease was 46.2% (36/78, 95% CI 34.8–57.8). With a median 8.7 months follow-up, the median time to progression was 3.1 months (95% CI 1.17–5.03) and the median overall survival (OS) was 7.8 months (95% CI 5.19–10.35). The median OS for patients with adenocarcinoma histology was 18.7 months compared to 6.1 months for non-adenocarcinoma. In a multivariate analysis, Eastern Cooperative Oncology Group performance status 0–1 [hazards ratio (HR)=0.331, 95% CI 0.135–0.814] and adenocarcinoma (HR=0.504, 95% CI 0.283–0.899) were independent factors for prolongation of overall survival.Conclusions Pemetrexed monotherapy has promising efficacy in patients with advanced NSCLC as a second-line therapy with less hematologic and non-hematologic toxicity, especially in those with adenocarcinoma histology. [Copyright &y& Elsevier]

Summary: Background: An irinotecan and cisplatin (IP) combination is one of active regimen used in treatment of extensive stage disease (ED) small cell lung cancer (SCLC). However, a 4-week cycle of irinotecan treatment can result in significant myelosuppression and diarrhea. Therefore, the present study was conducted to evaluate the efficacy and safety of biweekly IP in patients with ED SCLC. Methods: Patients with previously untreated ED SCLC received intravenous irinotecan at a dose of 60mg/m2 and cisplatin at a dose of 30mg/m2 on days 1 and 15 every 4 weeks. Results: Thirty-five patients were enrolled in this study. Three complete responses and 23 partial responses were confirmed, giving an overall response rate of 74.3%. After a median follow-up of 15.1 months, the median time to progression and overall survival were 7.7 months and 12.2 months, respectively. Grade 3/4 neutropenia occurred in seven patients and grade 3 febrile neutropenia was observed in one patient. Grade 3 diarrhea occurred in two patients. Conclusions: The combination chemotherapy of biweekly IP was found to be well tolerated and effective in patients with ED SCLC. Further evaluation of the combination of IP at the dose and schedule in this study is warranted in ED SCLC patients. [Copyright &y& Elsevier]