Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Beyond Progressive Disease: A Retrospective Analysis for Japanese Patients with Activating EGFR Mutations

IntroductionIt is not determined whether the continuous use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is reasonable for patients with activating EGFR mutations, who have progressed with the drug.MethodsWe retrospectively analyzed the data from 2002 to 2010 of consecutive patients who had advanced non–small-cell lung cancer (NSCLC) harboring activating EGFR mutations and showed radiological disease progression after EGFR-TKI treatment as the first-line or second-line setting. We classified them into two groups: continuous EGFR-TKI and switching to chemotherapy, and compared the clinical outcomes. Multivariate analysis for survival was performed including age, sex, Eastern Cooperative Oncology Group performance status (0–1/ 2–4), brain metastasis, EGFR mutations (deletions in exon 19 versus L858R), continuous EGFR-TKI (yes/no), and initiation of EGFR-TKI (first versus second).ResultsA total of 551 NSCLC patients were screened for EGFR mutations in the period, and 186 patients had activating EGFR mutations. To explore the potential use of EGFR-TKI beyond progressive disease (PD), 64 patients were selected and analyzed. There were 13 men and 51 women, and median age was 65.5 years (range, 42–86). Among them, 31 patients had deletions in exon 19, and 33 had point mutation of L858R in exon 21. Thirty-nine patients were continuing EGFR-TKI beyond PD; 25 patients were switched to cytotoxic chemotherapy alone. The median overall survival was 32.2 months in the patients continuing EGFR-TKI, and 23.0 months in the patients switching to chemotherapy, presenting a significant difference between the two groups (p = 0.005). Cox analysis showed that continuous EGFR-TKI after PD (hazards ratio 0.42, 95% confidence interval: 0.21–0.83, p = 0.013) was associated with improved survival.ConclusionContinuous use of EGFR-TKI beyond PD may prolong overall survival compared with switching to cytotoxic chemotherapy in patients with activating EGFR mutations. A prospective study will be needed to confirm our results

Combination therapy involving radiofrequency ablation and targeted chemotherapy with bevacizumab plus paclitaxel and cisplatin in a rabbit VX2 lung tumor model

Abstract Objective Radiofrequency ablation (RFA) is less effective for large tumors > 3 cm in diameter. Various studies of combination therapy using RFA and other treatments have been conducted to improve the results of RFA treatment of lung tumors, survival was extended in a tumor model when RFA was followed by concomitant use of systemic chemotherapy. Bevacizumab (BCM) is a one of molecular target drugs. Numerous clinical trials and reports have shown BCM’s effect when used in combination with cisplatin (CDDP) in lung tumor. Our objective is to evaluate the survival of concurrent, combined use of radiofrequency ablation and BCM, and platinum-doublet chemotherapy [CDDP/paclitaxel (PTX)] in a rabbit VX2 lung tumor. Results Survival times of the RFA alone, CDDP/PTX, CDDP/PTX/BCM, RFA/CDDP/PTX, and RFA/CDDP/PTX/BCM groups were significantly prolonged compared to that of the control group (P = 0.0055, P = 0.0055, P = 0.0004, P = 0.0002, P = 0.0019, respectively). Survival of the RFA/CDDP/PTX/BCM group was not significantly prolonged compared to the RFA alone (P = 0.53) and CDDP/PTX/BCM group (P = 0.68), while showing a significantly shorter survival time than that of the RFA/CDDP/PTX group (P = 0.017). The addition to BCM with combination RFA and systemic therapy with CDDP/PTX did not have a positive effect on survival

Characteristics of the Chiba Environmental Challenge Chamber

Background: An environmental challenge chamber (ECC), which we refer to as the α-chamber, was built at Chiba University in 2008. The aim of this study was to validate the functionality of the ECC. Methods: The stability of the pollen distribution and concentration in the ECC and symptoms of patients with Japanese cedar pollinosis induced by cedar pollen exposure were examined. Carryover effects of symptoms induced by different exposure protocols and correlations between symptoms induced in the ECC and those in the natural cedar pollen season were also determined. All the studies using the α-chamber were conducted out of the cedar pollen season. Results: The severity of symptoms in the chamber reached a peak about 2 hours after the start of pollen exposure and plateaued thereafter. After subjects left the chamber, the symptoms persisted for several days. There was no significant difference between the severity of symptoms at exposure levels of 8000 and 12000 grains/m3. The symptoms were significantly increased by exposure for 3 consecutive days; however, there were no carryover effects in a study performed with a two-week interval. The total nasal symptom score (TNSS) in the natural pollen season showed a weak correlation with the mean TNSS on the day of exposure and the following 3 days. Symptoms in the ECC also had weak correlations with those in the early natural pollen season. Conclusions: The ECC under well-controlled conditions is suitable for clinical studies and might accelerate development of treatment for seasonal allergic rhinitis. A complete evaluation requires inclusion of the persistent reaction after subjects leave the ECC