Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer

BACKGROUND: Gefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments. METHOD: We retrospectively evaluated the clinical courses of 27 NSCLC patients who received gefitinib and achieved either a complete or partial response. RESULTS: The best-response rate and disease-control rate against the initial chemotherapy for the gefitinib-responders were 27.3% and 77.3%, respectively. Favorable efficacy was observed in the primary lesion and metastases to the lung, liver and brain, while there was no obvious effect on bone metastasis. The primary lesion and intrapulmonary metastasis were the sites of major recurrence. Median progression-free survival was 13.8 months, median duration of gefitinib treatment was 17.0 months and median overall survival was 29.2 months. Some of the patients who experienced disease progression after responding to gefitinib were again sensitive to readministration of gefitinib following temporary cessation of gefitinib and other treatments. CONCLUSION: Patients may still be expected to have prolonged survival if they once responded to gefitinib and then underwent various subsequent treatments followed by readministration of gefitinib. These findings might provide valuable information for the management of gefitinib-responders

Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer

BACKGROUND: Gefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments. METHOD: We retrospectively evaluated the clinical courses of 27 NSCLC patients who received gefitinib and achieved either a complete or partial response. RESULTS: The best-response rate and disease-control rate against the initial chemotherapy for the gefitinib-responders were 27.3% and 77.3%, respectively. Favorable efficacy was observed in the primary lesion and metastases to the lung, liver and brain, while there was no obvious effect on bone metastasis. The primary lesion and intrapulmonary metastasis were the sites of major recurrence. Median progression-free survival was 13.8 months, median duration of gefitinib treatment was 17.0 months and median overall survival was 29.2 months. Some of the patients who experienced disease progression after responding to gefitinib were again sensitive to readministration of gefitinib following temporary cessation of gefitinib and other treatments. CONCLUSION: Patients may still be expected to have prolonged survival if they once responded to gefitinib and then underwent various subsequent treatments followed by readministration of gefitinib. These findings might provide valuable information for the management of gefitinib-responders

Adenoid cystic carcinoma of the peripheral lung: a case report

Adenoid cystic carcinoma of the peripheral lung is a rare entity. We recently encountered a patient with adenoid cystic carcinoma. A 75-year-old woman showed a nodular lesion with 10 mm in diameter in the right upper lung field on chest radiography. The diagnosis was unclear, but lung cancer could not be ruled out. Thoracoscopic biopsy was performed, and intraoperative pathological diagnosis revealed the carcinoma of the lung. We enforced upper lobectomy and mediastinal lymph node dissection to the patient. Histopathological examination revealed adenoid cystic carcinoma with a characteristic cribriform structure. Immunohistochemical examination revealed that the tumor cells were positive for thyroid transcription factor 1 (TTF-1), this tumor was diagnosed primary ACC of the lung

In situ study of fiber structure development of poly(butylene terephthalate) in a continuous laser-heated drawing process

The structural development of poly(butylene terephthalate) (PBT) fibers was analyzed using in situ wide angle X-ray diffraction and fiber temperature measurements during CO2 laser-heated drawing, in which the necking position on the running fiber could be fixed by CO2 laser irradiation. The measured parameters were determined as functions of the elapsed time after necking with a time resolution of 0.3 ms. The as-spun PBT fibers, which exhibited a low-oriented alpha-crystalline structure, were drawn to a draw ratio of 5 using laser heating. The (001') reflection, which indicates a quasi-smectic fibrillar structure, was not observed before crystallization in contrast to measurements of poly(ethylene terephthalate) (PET) and poly(ethylene 2,6-naphthalene dicarboxylate) (PEN). The alpha-crystal was transformed into an oriented beta-form crystal at the necking position, and the developed beta-crystallites exhibited increased size and altered orientation <2 ms after necking. The fiber temperature increased rapidly at around T-g, and the rearrangement of the beta-crystal primarily occurred as the fiber's temperature rose from 100 to 160 degrees C. The oriented beta-crystal of the drawn fiber transformed into the oriented beta-crystal when the drawing tension was released. Polymer Journal (2012) 44, 1030-1035; doi: 10.1038/pj.2012.65; published online 18 April 2012ArticlePOLYMER JOURNAL. 44(10):1030-1035 (2012)journal articl

GPCRomics : GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets

Financial support for these studies was provided by Roche, the Lymphoma and Leukemia Society, Friends of ANCHOR, an ASPET Astellas Award and grants from the National Institutes of Health, National Cancer Institute (CA189477, CA121938, CA155620). National Cancer Institute (NCI) Therapeutic Training Grant 5T32CA121938, NIH/NCI Research Grants R21 CA189477, an ASPET David Lehr Award and the Padres Pedal the Cause #PTC2017 award.Peer reviewedPublisher PD

Recent comparability of oceanographic nutrients data: Results of a 2003 intercomparison exercise using reference materials

An intercomparison exercise was conducted using the recently developed Reference Material for Nutrients in Seawater (RMNS). Discrepancies of reported values among laboratories were greater than the homogeneity of RMNS samples and the reported analytical precision of nutrients. The variability of in-house standards of the participating laboratories might be the most likely source of interlaboratory discrepancies. Therefore, the use of common reference materials, i.e. certified RM, is essential to establish and improve the comparability of nutrient data of the world's oceans

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2^ndEGFR-TKI administration.</p> <p>Methods</p> <p>We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.</p> <p>Results</p> <p>Three patients (27%) were treated with gefitinib as the 2^ndEGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2^ndEGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2^ndEGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2^ndEGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.</p> <p>Conclusions</p> <p>Our results indicate that a 2^ndEGFR-TKI treatment can be an effective treatment option for gefitinib responders.</p

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2^ndEGFR-TKI administration.</p> <p>Methods</p> <p>We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.</p> <p>Results</p> <p>Three patients (27%) were treated with gefitinib as the 2^ndEGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2^ndEGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2^ndEGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2^ndEGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.</p> <p>Conclusions</p> <p>Our results indicate that a 2^ndEGFR-TKI treatment can be an effective treatment option for gefitinib responders.</p

Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S768I and V769L.

Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) are associated with clinical responsiveness to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancers (NSCLCs). However, certain rare EGFR mutations including S768I are reported to confer less in vitro sensitivity to gefitinib, an EGFR-TKI, than major mutations such as exon 19 deletions and L858R and even the wild-type counterpart. Here, we report the first case of adenocarcinoma of the lung in which the patient had rare mutations S768I and V769L and was treated with gefitinib. Disease progressed during 6 weeks of treatment. This case suggests that in vitro sensitivity to gefitinib correlates with distinct clinical responsiveness to gefitinib in various types of EGFR mutations