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Background: Central nervous system (CNS) metastases caused by small-cell lung cancer (SCLC) are incurable and therefore fatal. Although such metastases are usually treated with chemotherapy or radiotherapy, their sensitivity to these treatment measures is unclear. Amrubicin appears to be a promising agent for relapsed SCLC, but its effectiveness in CNS metastases originating from SCLC is unknown., Methods: Between April 2002 and December 2009, 110 SCLC patients with CNS metastasis were treated at Shizuoka Cancer Center. Of these, we retrospectively reviewed 8 consecutive cases with CNS metastases originating from relapsed SCLC that were treated with amrubicin as a second-line therapy., Results: We recorded three sensitive relapses and five refractory cases. Amrubicin yielded a CNS response rate of 50 % (2 partial responses and 2 complete response; 95 % CI, 21.5-78.5\ %) and the disease control rate for CNS lesions was 87.5 % (95 % CI, 52.9-97.8 %). All of the sensitive relapse patients achieved a partial response. The median time to progression for CNS metastases was 150.5 days (95 % CI, 9-171 days), and the median survival time from the start of amrubicin administration was 230.5 days (95 % CI, 89-619 days). We also report a dramatic improvement in one patient's radiological result of intramedullary spinal cord metastasis and alleviation of her symptoms following amrubicin monotherapy including this case series., Conclusions: The results of this study suggest that amrubicin is active in patients with CNS metastases originating from SCLC.

Introduction: Based on previous reports, patients who experience isolated central nervous system (CNS) failure may not have systemic acquired resistance to EGFR-TKI therapy. However, because there are few articles that have reported on the clinical efficacy of continuous EGFR-TKI administration following progressive disease (PD) in isolated CNS metastasis, we retrospectively investigated the possibility of using the treatment., Patients and Methods: From July 2002 to December 2009, 17 non-small cell lung cancer patients showed isolated CNS failure after clinical benefit (partial response or stable disease longer than 6 months) from EGFR-TKIs and continuously received EGFR-TKIs following radiotherapy (whole brain radiotherapy or stereotactic radiotherapy) to the CNS metastases., Results: The response rate and the disease control rate of CNS lesions were 41% and 76%, respectively. The median progression free survival, extracranial progression free survival and the median overall survival time were 80 days, 171 days and 403 days, respectively. The toxicities which were observed during the first EGFR-TKI treatments were sustained, but did not worsen during this study period. The acute toxicities caused by radiotherapy to the CNS were controllable. There were no remarkable late toxicities related to the treatment., Conclusions: Continuous administration of EGFR-TKI following radiotherapy after PD in isolated CNS metastasis appears to be a valid treatment option., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The efficacy of gefitinib for patients with non-adenocarcinoma non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is unclear, because only a small percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for tumors harboring EGFR mutation were non-adenocarcinoma NSCLC. A pooled analysis was conducted to clarify the efficacy of gefitinib for non-adenocarcinoma NSCLC patients harboring EGFR mutations. A systematic search of the PUBMED databases was conducted to identify all clinical reports that contained advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations and treated with gefitinib. The selected patients were advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations who were treated with gefitinib and described in reports containing the data of the histology, status of EGFR mutations and response to gefitinib. This study selected 33 patients from 15 reports. Twenty-seven and three of the 33 patients were squamous cell carcinoma and adenosquamous cell carcinoma, respectively. One patient each had large-cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma. Twenty-one patients (64%) had sensitive EGFR mutations. The response rate (RR), disease control rate (DCR) and median progression-free survival (mPFS) was 27%, 67-70% and 3.0 months, respectively. These factors were statistically significantly inferior in the non-adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations selected from the same published reports (RR: 27%vs 66%, P = 0.000028; DCR: 67-70%vs 92-93%, P = 0.000014; mPFS: 3.0 vs 9.4 months, P = 0.0001, respectively). Gefitinib is less effective in non-adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations., (© 2011 Japanese Cancer Association.)

Background: Elevated levels of N-telopeptide of type I collagen (NTX) are associated with skeletal-related events and death. However, it is unclear whether NTX is useful for monitoring therapeutic response in non-small cell lung cancer (NSCLC) patients with bone metastases., Patients and Methods: Urinary NTX levels were assessed at baseline and after one cycle of chemotherapy in 30 NSCLC patients with bone metastases. NTX levels were categorized as normal (NTX <64 nmol/mmol creatinine) or high (NTX ≥64 nmol/mmol creatinine)., Results: In 30 patients, the median NTX level at 1 month was significantly lower than that at baseline (P = 0.0016). The NTX levels after treatment were significantly lower than those at baseline in 20 patients with partial response (n = 2) or stable disease (n = 18). However, no significant difference of the NTX levels was observed in 10 patients with progressive disease. Sixteen (53.3%) of 30 patients had high baseline NTX levels. Ten patients had normal NTX levels after one cycle of chemotherapy, whereas 6 patients also had high NTX levels after treatment. The 10 patients with normal NTX levels had significantly better prognosis than the 6 patients with high NTX levels., Conclusion: Urinary NTX levels at 1 month after chemotherapy may be useful for predicting therapeutic response in NSCLC patients with bone metastases. Normalization of elevated baseline NTX at 1 month after chemotherapy was associated with survival benefits.

Purpose: The use of erlotinib after gefitinib failure in patients with non-small cell lung cancer (NSCLC) is not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the effectiveness of erlotinib after failure of gefitinib., Methods: We searched published reports including erlotinib and gefitinib. Eleven reports were identified (published between November 2004 and December 2008). Advanced NSCLC who documented progressive disease (PD) for gefitinib 250 mg/day, received erlotinib 150 mg once daily., Results: A total of 106 patients were pooled from these studies. Asian was observed in 70.8%, women in 72.6%, adenocarcinoma in 85.1%, never smoker in 75.3%. In erlotinib therapy, there was observed in 9.9% in partial response (PR), 18.9% in stable disease (SD) and 70.8% in PD. Disease control (DC) rate for gefitinib and erlotinib was 71.7% and 29.2%, respectively. No significant difference of disease control rate (37.5% vs 21.7%, p=0.1503) and response rate (6.3% vs 8.7%, p=1.000) was observed between patients with EGFR mutations and those with wild type EGFR. The significantly different response on erlotinib therapy was observed in patients who had shown SD for gefitinib therapy (p=0.0095) and those who had a PFS of more than 6 months during gefitinib treatment (p=0.0261). The common toxicities were skin rash and diarrhea., Conclusion: Erlotinib may produce clinical benefits in patients who had shown long SD on prior gefitinib therapy. Moreover, EGFR mutations were not positive predictors for erlotinib response after gefitinib failure., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: No investigation of S-1 monotherapy in previously treated advanced non-small-cell lung cancer (NSCLC) patients has yet been reported. We conducted a retrospective study to evaluate the efficacy and tolerability of S-1 in patients with failure of second- or further-line chemotherapy., Patients and Methods: The records of NSCLC patients who had received S-1 monotherapy between January 2005 and November 2006 with the following eligibility criteria were reviewed: previously treated with at least two regimens including platinum and docetaxel in the case of nonadenocarcinoma patients, and including platinum, docetaxel and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in the case of adenocarcinoma patients. S-1 was administered for 28 consecutive days, followed by a 14-day drug-free period (42 days in one course). The drug was administered in two divided doses daily at 80 mg/day for patients with a body surface area <1.25 m(2), 100 mg/day for those with a body surface area of 1.25-1.5 m(2), and 120 mg/day for those with a body surface area > or = 1.5 m(2)., Results: Thirty-five patients were registered. The median number of courses administered per patient was 2 (range 1-9). The toxicity profile was mild, and grade 3 or more severe toxicity was rare. The overall response and disease control rates were 5.7% and 40%, respectively. The median survival time was 208 days., Conclusion: S-1 exhibits modest activity and acceptable toxicity when used as a third or subsequent line of chemotherapy in patients with advanced NSCLC.