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Boon Cher Goh - One of the best experts on this subject based on the ideXlab platform.
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Rapid determination of Gefitinib and its main metabolite, O-desmethyl Gefitinib in human plasma using liquid chromatography-tandem mass spectrometry.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2011Co-Authors: Lingzhi Wang, Michelle Yi-xiu Lim, Tan Min Chin, Win Lwin Thuya, Pei-ling Nye, Andrea Li Ann Wong, Sui Yung Chan, Boon Cher GohAbstract:Abstract A novel, rapid and specific liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed and validated for the simultaneous quantification of Gefitinib and its predominant metabolite, O-desmethyl Gefitinib in human plasma. Chromatographic separation of analytes was achieved on an Alltima C18 analytical HPLC column (150 mm × 2.1 mm, 5 μm) using an isocratic elution mode with a mobile phase comprised acetonitrile and 0.1% formic acid in water (30:70, v/v). The flow rate was 300 μL/min. The chromatographic run time was 3 min. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionization (ESI) in positive mode. Linearity was demonstrated in the range of 5–1000 ng/mL for Gefitinib and 5–500 ng/mL for O-desmethyl Gefitinib. The intra- and inter-day precisions for Gefitinib and O-desmethyl Gefitinib were ≤10.8% and the accuracies ranged from 89.7 to 104.7% for Gefitinib and 100.4 to 106.0% for O-desmethyl Gefitinib. This method was used as a bioanalytical tool in a phase I clinical trial to investigate the possible effect of hydroxychloroquine on the pharmacokinetics of Gefitinib. The results of this study enabled clinicians to ascertain the safety of the combination therapy of hydroxychloroquine and Gefitinib in patients with advanced (Stage IIIB–IV) non-small cell lung cancer (NSCLC).
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Rapid determination of Gefitinib and its main metabolite, O-desmethyl Gefitinib in human plasma using liquid chromatography–tandem mass spectrometry
Journal of Chromatography A, 2011Co-Authors: Lingzhi Wang, Michelle Yi-xiu Lim, Tan Min Chin, Win Lwin Thuya, Pei-ling Nye, Andrea Li Ann Wong, Sui Yung Chan, Boon Cher GohAbstract:A novel, rapid and specific liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed and validated for the simultaneous quantification of Gefitinib and its predominant metabolite, O-desmethyl Gefitinib in human plasma. Chromatographic separation of analytes was achieved on an Alltima C18 analytical HPLC column (150mm×2.1mm, 5μm) using an isocratic elution mode with a mobile phase comprised acetonitrile and 0.1% formic acid in water (30:70, v/v). The flow rate was 300μL/min. The chromatographic run time was 3min. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionization (ESI) in positive mode. Linearity was demonstrated in the range of 5–1000ng/mL for Gefitinib and 5–500ng/mL for O-desmethyl Gefitinib. The intra- and inter-day precisions for Gefitinib and O-desmethyl Gefitinib were ≤10.8% and the accuracies ranged from 89.7 to 104.7% for Gefitinib and 100.4 to 106.0% for O-desmethyl Gefitinib. This method was used as a bioanalytical tool in a phase I clinical trial to investigate the possible effect of hydroxychloroquine on the pharmacokinetics of Gefitinib. The results of this study enabled clinicians to ascertain the safety of the combination therapy of hydroxychloroquine and Gefitinib in patients with advanced (Stage IIIB–IV) non-small cell lung cancer (NSCLC).
Lingzhi Wang - One of the best experts on this subject based on the ideXlab platform.
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Rapid determination of Gefitinib and its main metabolite, O-desmethyl Gefitinib in human plasma using liquid chromatography-tandem mass spectrometry.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2011Co-Authors: Lingzhi Wang, Michelle Yi-xiu Lim, Tan Min Chin, Win Lwin Thuya, Pei-ling Nye, Andrea Li Ann Wong, Sui Yung Chan, Boon Cher GohAbstract:Abstract A novel, rapid and specific liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed and validated for the simultaneous quantification of Gefitinib and its predominant metabolite, O-desmethyl Gefitinib in human plasma. Chromatographic separation of analytes was achieved on an Alltima C18 analytical HPLC column (150 mm × 2.1 mm, 5 μm) using an isocratic elution mode with a mobile phase comprised acetonitrile and 0.1% formic acid in water (30:70, v/v). The flow rate was 300 μL/min. The chromatographic run time was 3 min. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionization (ESI) in positive mode. Linearity was demonstrated in the range of 5–1000 ng/mL for Gefitinib and 5–500 ng/mL for O-desmethyl Gefitinib. The intra- and inter-day precisions for Gefitinib and O-desmethyl Gefitinib were ≤10.8% and the accuracies ranged from 89.7 to 104.7% for Gefitinib and 100.4 to 106.0% for O-desmethyl Gefitinib. This method was used as a bioanalytical tool in a phase I clinical trial to investigate the possible effect of hydroxychloroquine on the pharmacokinetics of Gefitinib. The results of this study enabled clinicians to ascertain the safety of the combination therapy of hydroxychloroquine and Gefitinib in patients with advanced (Stage IIIB–IV) non-small cell lung cancer (NSCLC).
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Rapid determination of Gefitinib and its main metabolite, O-desmethyl Gefitinib in human plasma using liquid chromatography–tandem mass spectrometry
Journal of Chromatography A, 2011Co-Authors: Lingzhi Wang, Michelle Yi-xiu Lim, Tan Min Chin, Win Lwin Thuya, Pei-ling Nye, Andrea Li Ann Wong, Sui Yung Chan, Boon Cher GohAbstract:A novel, rapid and specific liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed and validated for the simultaneous quantification of Gefitinib and its predominant metabolite, O-desmethyl Gefitinib in human plasma. Chromatographic separation of analytes was achieved on an Alltima C18 analytical HPLC column (150mm×2.1mm, 5μm) using an isocratic elution mode with a mobile phase comprised acetonitrile and 0.1% formic acid in water (30:70, v/v). The flow rate was 300μL/min. The chromatographic run time was 3min. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionization (ESI) in positive mode. Linearity was demonstrated in the range of 5–1000ng/mL for Gefitinib and 5–500ng/mL for O-desmethyl Gefitinib. The intra- and inter-day precisions for Gefitinib and O-desmethyl Gefitinib were ≤10.8% and the accuracies ranged from 89.7 to 104.7% for Gefitinib and 100.4 to 106.0% for O-desmethyl Gefitinib. This method was used as a bioanalytical tool in a phase I clinical trial to investigate the possible effect of hydroxychloroquine on the pharmacokinetics of Gefitinib. The results of this study enabled clinicians to ascertain the safety of the combination therapy of hydroxychloroquine and Gefitinib in patients with advanced (Stage IIIB–IV) non-small cell lung cancer (NSCLC).
Kazuto Nishio - One of the best experts on this subject based on the ideXlab platform.
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tak 701 a humanized monoclonal antibody to hepatocyte growth factor reverses Gefitinib resistance induced by tumor derived hgf in non small cell lung cancer with an egfr mutation
Molecular Cancer Therapeutics, 2010Co-Authors: Wataru Okamoto, Kazuto Nishio, Isamu Okamoto, Erina Hatashita, Y Yamada, Kiyoko Kuwata, Kaoru Tanaka, Haruka Yamaguchi, Tokuzo Arao, Masahiro FukuokaAbstract:Most non–small cell lung cancer (NSCLC) tumors with an activating mutation of the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (TKI) such as Gefitinib but ultimately develop resistance to these drugs. Hepatocyte growth factor (HGF) induces EGFR-TKI resistance in NSCLC cells with such a mutation. We investigated strategies to overcome Gefitinib resistance induced by HGF. Human NSCLC cells with an activating EGFR mutation (HCC827 cells) were engineered to stably express HGF (HCC827-HGF cells). HCC827-HGF cells secreted large amounts of HGF and exhibited resistance to Gefitinib in vitro to an extent similar to that of HCC827 GR cells, in which the gene for the HGF receptor MET is amplified. A MET-TKI reversed Gefitinib resistance in HCC827-HGF cells as well as in HCC827 GR cells, suggesting that MET activation induces Gefitinib resistance in both cell lines. TAK-701, a humanized monoclonal antibody to HGF, in combination with Gefitinib inhibited the phosphorylation of MET, EGFR, extracellular signal-regulated kinase, and AKT in HCC827-HGF cells, resulting in suppression of cell growth and indicating that autocrine HGF-MET signaling contributes to Gefitinib resistance in these cells. Combination therapy with TAK-701 and Gefitinib also markedly inhibited the growth of HCC827-HGF tumors in vivo . The addition of TAK-701 to Gefitinib is a promising strategy to overcome EGFR-TKI resistance induced by HGF in NSCLC with an activating EGFR mutation. Mol Cancer Ther; 9(10); OF1–8. ©2010 AACR.
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effects of src inhibitors on cell growth and epidermal growth factor receptor and met signaling in Gefitinib resistant non small cell lung cancer cells with acquired met amplification
Cancer Science, 2010Co-Authors: Takeshi Yoshida, Kazuto Nishio, Pasi A Janne, Isamu Okamoto, Wataru Okamoto, Erina Hatashita, Y Yamada, Kiyoko Kuwata, Masahiro Fukuoka, Kazuhiko NakagawaAbstract:The efficacy of epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors such as Gefitinib and erlotinib in non-small cell lung cancer (NSCLC) is often limited by the emergence of drug resistance conferred either by a secondary T790M mutation of EGFR or by acquired amplification of the MET gene. We now show that the extent of activation of the tyrosine kinase Src is markedly increased in Gefitinib-resistant NSCLC (HCC827 GR) cells with MET amplification compared with that in the Gefitinib-sensitive parental (HCC827) cells. In contrast, the extent of Src activation did not differ between Gefitinib-resistant NSCLC (PC9 ⁄ZD) cells harboring the T790M mutation of EGFR and the corresponding Gefitinib-sensitive parental (PC9) cells. This activation of Src in HCC827 GR cells was largely abolished by the MET-TKI PHA-665752 but was only partially inhibited by Gefitinib, suggesting that Src activation is more dependent on MET signaling than on EGFR signaling in Gefitinib-resistant NSCLC cells with MET amplification. Src inhibitors blocked Akt and Erk signaling pathways, resulting in both suppression of cell growth and induction of apoptosis, in HCC827 GR cells as effectively as did the combination of Gefitinib and PHA-665752. Furthermore, Src inhibitor dasatinib inhibited tumor growth in HCC827 GR xenografts to a significantly greater extent than did treatment with Gefitinib alone. These results provide a rationale for clinical targeting of Src in Gefitinib-resistant NSCLC with MET amplification. (Cancer Sci 2010; 101: 167‐172)
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addition of s 1 to the epidermal growth factor receptor inhibitor Gefitinib overcomes Gefitinib resistance in non small cell lung cancer cell lines with met amplification
Clinical Cancer Research, 2009Co-Authors: Takafumi Okabe, Kazuto Nishio, Takeshi Yoshida, Isamu Okamoto, Erina Hatashita, Y Yamada, Masahiro Fukuoka, Sayaka Tsukioka, Junji Uchida, Pasi A JanneAbstract:Purpose: Most non–small cell lung cancer (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR-TKI) such as Gefitinib and erlotinib, but they almost invariably develop resistance to these drugs. A secondary mutation in EGFR (T790M) and amplification of the MET proto-oncogene have been identified as mechanisms of such acquired resistance to EGFR-TKIs. We have now investigated whether addition of the oral fluoropyrimidine derivative S-1 to Gefitinib might overcome Gefitinib resistance in NSCLC cell lines. Experimental Design: The effects of Gefitinib on EGFR signaling and on the expression both of thymidylate synthase and of the transcription factor E2F-1 in Gefitinib-resistant NSCLC cells were examined by immunoblot analysis. The effects of S-1 (or 5-fluorouracil) and Gefitinib on the growth of NSCLC cells were examined in vitro as well as in nude mice. Results: Gefitinib induced down-regulation of thymidylate synthase and E2F-1 in Gefitinib-resistant NSCLC cells with MET amplification but not in those harboring the T790M mutation of EGFR . The combination of 5-fluorouracil and Gefitinib synergistically inhibited the proliferation of cells with MET amplification, but not that of those with the T790M mutation of EGFR, in vitro . Similarly, the combination of S-1 and Gefitinib synergistically inhibited the growth only of NSCLC xenografts with MET amplification. Conclusions: Our results suggest that the addition of S-1 to EGFR-TKIs is a promising strategy to overcome EGFR-TKI resistance in NSCLC with MET amplification.
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Drug Accumulation and Efflux Do not Contribute to Acquired Gefitinib Resistance
New Trends in the Molecular and Biological Basis for Clinical Oncology, 2009Co-Authors: Sojiro Kusumoto, Kazuto Nishio, Tomohide Sugiyama, Masanao Nakashima, Toshimitsu Yamaoka, Takashi Hirose, Tsukasa Ohnishi, Naoya Horichi, Mitsuru Adachi, Nagahiro SaijoAbstract:Gefitinib is one of tyrosine kinase inhibitors and often has dramatic effect on non-small-cell lung cancer (NSCLC) expressed mutant EGFR. However, most of the patients who respond to Gefitinib eventually experience tumor recurrence. To clarify the mechanism of this acquired resistance, we examined cellular accumulation and efflux of Gefitinib using Gefitinib sensitive and resistant NSCLC cells. We used four NSCLC cell lines; PC-9: hypersensitive to Gefitinib, expressed a 15 bp deletion mutant EGFR, PC-9/ZD2001 and PC-9/ZD1kl: acquired-resistant to Gefitinib, PC-9/ZD2001R: a revertant reacquired sensitivity to Gefitinib. To measure the cellular accumulation, cells were exposed to 1 µM of [14C]Gefitinib for 3 to 30 min at 37 °C For the measuring of drug efflux, cells were exposed Gefitinib for 30 min, and then cells were washed and further incubated in drug free medium. After the incubation, cells were lysed and the radioactivities were counted. There was no significant difference of Gefitinib accumulation in those cell lines (range 642–731 µmol/g protein at 30 min). The efficiencies of Gefitinib-efflux were almost the same in those cell lines (about 80% of gefitinb was discharged at 15 min). According these findings, we demonstrated that acquired resistance to Gefitinib did not depend on cellular accumulation or efflux of this drug.
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Effects of different combinations of Gefitinib and irinotecan in lung cancer cell lines expressing wild or deletional EGFR
Lung Cancer, 2006Co-Authors: Tatsu Shimoyama, Fumiaki Koizumi, Katsuyuki Kiura, Hisao Fukumoto, Mitsune Tanimoto, Nagahiro Saijo, Kazuto NishioAbstract:EGFR mutations are a major determinant of lung tumor response to Gefitinib, an EGFR-specific tyrosine kinase inhibitor. Obtaining a response from lung tumors expressing wild-type EGFR is a major obstacle. The combination of Gefitinib and cytotoxic drugs is one strategy against lung cancers expressing wild-type EGFR. The DNA topoisomerase inhibitor irinotecan sulfate (CPT-11) is active against lung cancer. We examined the sensitivity of lung cancers expressing wild- or mutant-type EGFR to the combination of Gefitinib and CPT-11. The in vitro effect of Gefitinib and SN-38 (the active metabolite of CPT-11) was examined in seven lung cancer cell lines using the dye formation assay with a combination index. When administered concurrently, Gefitinib and SN-38 had a synergistic effect in five of the seven cell lines expressing wild-type EGFR, whereas the combination was antagonistic in PC-9 cells and a PC-9 subline resistant to Gefitinib and expressing deletional mutant EGFR (PC-9/ZD). When administered sequentially, treatment with SN-38 followed by Gefitinib had remarkable synergistic effects in the PC-9 and PC-9/ZD cells. In an in vivo tumor-bearing model, this combination had a schedule-dependent synergistic effect in the PC-9 and PC-9/ZD cells. An immunohistochemical analysis of the tumors in mice treated with CPT-11 and Gefitinib demonstrated that the number of Ki-67 positive tumor cells induced by CPT-11 treatment was decreased when CPT-11 was administered in combination with Gefitinib. In conclusion, the sequential combination of CPT-11 and Gefitinib is considered to be active against lung cancer.
Yasuo Saijo - One of the best experts on this subject based on the ideXlab platform.
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Phase II study of Gefitinib readministration in patients with advanced non-small cell lung cancer and previous response to Gefitinib.
Oncology, 2010Co-Authors: Hajime Asahina, Akira Inoue, Makoto Maemondo, Satoshi Oizumi, Ichiro Kinoshita, Noriaki Sukoh, Masao Harada, Takashi Ishida, Yuka Fujita, Yasuo SaijoAbstract:Salvage treatment for acquired resistance to Gefitinib has yet to be developed. We conducted the first prospective phase II study of Gefitinib readministration in previous Gefitinib responders. Gefitinib (250 mg/day) was readministered to patients with advanced/metastatic non-small cell lung cancer who had achieved objective response to initial Gefitinib and subsequently received cytotoxic chemotherapy after disease progression with initial Gefitinib. The primary endpoint was the objective response rate with Gefitinib readministration. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), quality of life, and toxicity. Changes in lung cancer-related symptoms were evaluated using the seven-item lung cancer subscale of the questionnaire. Sixteen patients were enrolled between February 2005 and January 2008. Most had received ≥3 regimens of chemotherapy. Response and disease-control rates for all patients were 0 and 44%. Median PFS and OS were 2.5 and 14.7 months, respectively. Four of 7 patients with stable disease experienced a long duration (≥6 months) of disease control without severe toxicity. Symptom improvement was observed in 2 of 12 patients (17%) for whom quality of life was evaluable. Gefitinib represents a useful therapeutic option for selected previous Gefitinib responders. Copyright © 2011 S. Karger AG, Basel.
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Phase II study of Gefitinib readministration in patients with advanced non-small cell lung cancer and previous response to Gefitinib.
Oncology, 2010Co-Authors: Hajime Asahina, Akira Inoue, Satoshi Oizumi, Ichiro Kinoshita, Noriaki Sukoh, Masao Harada, Takashi Ishida, Yuka Fujita, M. Maemondo, Yasuo SaijoAbstract:Objective: Salvage treatment for acquired resistance to Gefitinib has yet to be developed. We conducted the first prospective phase II study of Gefitinib readministration in previous Gefitinib responders. Methods: Gefitinib (250 mg/day) was readministered to patients with advanced/metastatic non-small cell lung cancer who had achieved objective response to initial Gefitinib and subsequently received cytotoxic chemotherapy after disease progression with initial Gefitinib. The primary endpoint was the objective response rate with Gefitinib readministration. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), quality of life, and toxicity. Changes in lung cancer-related symptoms were evaluated using the seven-item lung cancer subscale of the questionnaire. Results: Sixteen patients were enrolled between February 2005 and January 2008. Most had received ≧3 regimens of chemotherapy. Response and disease-control rates for all patients were 0 and 44%. Median PFS and OS were 2.5 and 14.7 months, respectively. Four of 7 patients with stable disease experienced a long duration (≧6 months) of disease control without severe toxicity. Symptom improvement was observed in 2 of 12 patients (17%) for whom quality of life was evaluable. Conclusion: Gefitinib represents a useful therapeutic option for selected previous Gefitinib responders.
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first line Gefitinib versus first line chemotherapy by carboplatin cbdca plus paclitaxel txl in non small cell lung cancer nsclc patients pts with egfr mutations a phase iii study 002 by north east japan Gefitinib study group
Journal of Clinical Oncology, 2009Co-Authors: Kunihiko Kobayashi, Akira Inoue, Makoto Maemondo, Shunichi Sugawara, Hiroshi Isobe, Satoshi Oizumi, Yasuo Saijo, Akihiko Gemma, S Morita, Koichi HagiwaraAbstract:8016 Background: Based on our promising results of phase II studies estimating Gefitinib in NSCLC pts with sensitive EGFR mutations (JCO 2006, BJC 2006), this multicenter phase III trial compared progression free survival (PFS) of first line Gefitinib versus first line chemotherapy in EGFR mutation positive pts with stage IIIB/IV NSCLC. Per protocol, an analysis for safety except response, PFS and overall survival were estimated. Methods: PNA-LNA PCR clamp test, which had been developed and validated by us (Cancer Res 2005, Cancer Sci 2007), was employed to detect EGFR mutations using cytological samples or histological samples. Pts having sensitive EGFR mutations, measurable site(s), ECOG PS 0–1, age of 20–75 years, and no prior chemotherapy were randomized (1:1 ratio; balanced for institution, sex, and stage) to receive Arm A: gefitinb (250 mg/ day) orally, or Arms B: CBDCA AUC 6 and TXL 200mg/m2 in 21-day cycles until disease progression. The primary endpoint was PFS, and the sample size was calculated...
Ichiro Kinoshita - One of the best experts on this subject based on the ideXlab platform.
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Gefitinib or chemotherapy for non small cell lung cancer with mutated egfr
The New England Journal of Medicine, 2010Co-Authors: Makoto Maemondo, Kunihiko Kobayashi, Akira Inoue, Shunichi Sugawara, Hiroshi Isobe, Satoshi Oizumi, Akihiko Gemma, Masao Harada, Hirohisa Yoshizawa, Ichiro KinoshitaAbstract:In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the Gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with Gefitinib, 0.36; P<0.001), resulting in early termination of the study. The Gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the Gefitinib group and 23.6 months in the chemotherapy group (P = 0.31). The most common adverse events in the Gefitinib group were rash (71.1%) and elevated amino transferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving Gefitinib died from interstitial lung disease. CONCLUSIONS First-line Gefitinib for patients with advanced non–small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)
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Phase II study of Gefitinib readministration in patients with advanced non-small cell lung cancer and previous response to Gefitinib.
Oncology, 2010Co-Authors: Hajime Asahina, Akira Inoue, Makoto Maemondo, Satoshi Oizumi, Ichiro Kinoshita, Noriaki Sukoh, Masao Harada, Takashi Ishida, Yuka Fujita, Yasuo SaijoAbstract:Salvage treatment for acquired resistance to Gefitinib has yet to be developed. We conducted the first prospective phase II study of Gefitinib readministration in previous Gefitinib responders. Gefitinib (250 mg/day) was readministered to patients with advanced/metastatic non-small cell lung cancer who had achieved objective response to initial Gefitinib and subsequently received cytotoxic chemotherapy after disease progression with initial Gefitinib. The primary endpoint was the objective response rate with Gefitinib readministration. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), quality of life, and toxicity. Changes in lung cancer-related symptoms were evaluated using the seven-item lung cancer subscale of the questionnaire. Sixteen patients were enrolled between February 2005 and January 2008. Most had received ≥3 regimens of chemotherapy. Response and disease-control rates for all patients were 0 and 44%. Median PFS and OS were 2.5 and 14.7 months, respectively. Four of 7 patients with stable disease experienced a long duration (≥6 months) of disease control without severe toxicity. Symptom improvement was observed in 2 of 12 patients (17%) for whom quality of life was evaluable. Gefitinib represents a useful therapeutic option for selected previous Gefitinib responders. Copyright © 2011 S. Karger AG, Basel.
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Phase II study of Gefitinib readministration in patients with advanced non-small cell lung cancer and previous response to Gefitinib.
Oncology, 2010Co-Authors: Hajime Asahina, Akira Inoue, Satoshi Oizumi, Ichiro Kinoshita, Noriaki Sukoh, Masao Harada, Takashi Ishida, Yuka Fujita, M. Maemondo, Yasuo SaijoAbstract:Objective: Salvage treatment for acquired resistance to Gefitinib has yet to be developed. We conducted the first prospective phase II study of Gefitinib readministration in previous Gefitinib responders. Methods: Gefitinib (250 mg/day) was readministered to patients with advanced/metastatic non-small cell lung cancer who had achieved objective response to initial Gefitinib and subsequently received cytotoxic chemotherapy after disease progression with initial Gefitinib. The primary endpoint was the objective response rate with Gefitinib readministration. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), quality of life, and toxicity. Changes in lung cancer-related symptoms were evaluated using the seven-item lung cancer subscale of the questionnaire. Results: Sixteen patients were enrolled between February 2005 and January 2008. Most had received ≧3 regimens of chemotherapy. Response and disease-control rates for all patients were 0 and 44%. Median PFS and OS were 2.5 and 14.7 months, respectively. Four of 7 patients with stable disease experienced a long duration (≧6 months) of disease control without severe toxicity. Symptom improvement was observed in 2 of 12 patients (17%) for whom quality of life was evaluable. Conclusion: Gefitinib represents a useful therapeutic option for selected previous Gefitinib responders.
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Clinical benefit of readministration of Gefitinib for initial Gefitinib-responders with non-small cell lung cancer.
BMC cancer, 2007Co-Authors: Hiroshi Yokouchi, Koichi Yamazaki, Ichiro Kinoshita, Jun Konishi, Hajime Asahina, Noriaki Sukoh, Masao Harada, Kenji Akie, Shigeaki Ogura, Takashi IshidaAbstract: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.
