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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. (Cancer Sci 2011; 102: 1032–1037)

Summary 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.

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.

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 ≥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.

Background Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose ( 18 F-FDG) has been studied in thymic epithelial tumors. We evaluated the usefulness of 18 F-FDG PET for monitoring after treatment in unresectable thymic epithelial tumors. Method Twelve patients with unresectable/metastatic thymic epithelial tumors underwent PET study with 18 F-FDG before and after chemotherapy or radiotherapy. Response and survival were analyzed according to the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of the mediastinum (T/M ratio). Results Partial response (PR) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) was noted in 4 (33%) of 12 patients, and partial metabolic response (PMR) was observed in 6 (50%) of 12 patients. PR was observed in 4 of 6 patients with PMR. In 6 patients with any response, the T/M ratio at post-treatment was significantly lower than at baseline ( p  = 0.0017). In 6 patients with stable disease (SD), stable metabolic disease (SMD) was observed in 5 by use of 18 F-FDG PET. No statistically significant difference of 18 F-FDG uptake between at baseline and post-therapy was observed in 6 patients with SD ( p  = 0.4157) and SMD ( p  = 0.8419). Although the overall survival after treatment showed no statistically significant difference between PMR and SMD or progressive metabolic disease in the whole group of patients including thymoma, a statistically significant difference in the overall survival was observed between 5 patients with PMR and 5 patients with non-PMR ( p  = 0.0280). Conclusion Our preliminary study suggests that 18 F-FDG PET is useful for monitoring response and outcome after treatment in unresectable thymic epithelial tumors.

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 3.0months, 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 9.4months, P=0.0001, respectively). Gefitinib is less effective in non-adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations. (Cancer Sci 2011; 102: 1032-1037)

Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (^sup 18^F-FDG) has been studied in thymic epithelial tumors. We evaluated the usefulness of ^sup 18^F-FDG PET for monitoring after treatment in unresectable thymic epithelial tumors. Twelve patients with unresectable/metastatic thymic epithelial tumors underwent PET study with ^sup 18^F-FDG before and after chemotherapy or radiotherapy. Response and survival were analyzed according to the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of the mediastinum (T/M ratio). Partial response (PR) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) was noted in 4 (33%) of 12 patients, and partial metabolic response (PMR) was observed in 6 (50%) of 12 patients. PR was observed in 4 of 6 patients with PMR. In 6 patients with any response, the T/M ratio at post-treatment was significantly lower than at baseline (p = 0.0017). In 6 patients with stable disease (SD), stable metabolic disease (SMD) was observed in 5 by use of ^sup 18^F-FDG PET. No statistically significant difference of ^sup 18^F-FDG uptake between at baseline and post-therapy was observed in 6 patients with SD (p = 0.4157) and SMD (p = 0.8419). Although the overall survival after treatment showed no statistically significant difference between PMR and SMD or progressive metabolic disease in the whole group of patients including thymoma, a statistically significant difference in the overall survival was observed between 5 patients with PMR and 5 patients with non-PMR (p = 0.0280). Our preliminary study suggests that ^sup 18^F-FDG PET is useful for monitoring response and outcome after treatment in unresectable thymic epithelial tumors.[PUBLICATION ABSTRACT]

Background: Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose ( super(18)F-FDG) has been studied in thymic epithelial tumors. We evaluated the usefulness of super(18)F-FDG PET for monitoring after treatment in unresectable thymic epithelial tumors. Method: Twelve patients with unresectable/metastatic thymic epithelial tumors underwent PET study with super(18)F-FDG before and after chemotherapy or radiotherapy. Response and survival were analyzed according to the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of the mediastinum (T/M ratio). Results: Partial response (PR) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) was noted in 4 (33%) of 12 patients, and partial metabolic response (PMR) was observed in 6 (50%) of 12 patients. PR was observed in 4 of 6 patients with PMR. In 6 patients with any response, the T/M ratio at post-treatment was significantly lower than at baseline (p=0.0017). In 6 patients with stable disease (SD), stable metabolic disease (SMD) was observed in 5 by use of super(18)F-FDG PET. No statistically significant difference of super(18)F-FDG uptake between at baseline and post-therapy was observed in 6 patients with SD (p=0.4157) and SMD (p=0.8419). Although the overall survival after treatment showed no statistically significant difference between PMR and SMD or progressive metabolic disease in the whole group of patients including thymoma, a statistically significant difference in the overall survival was observed between 5 patients with PMR and 5 patients with non-PMR (p=0.0280). Conclusion: Our preliminary study suggests that super(18)F-FDG PET is useful for monitoring response and outcome after treatment in unresectable thymic epithelial tumors.