Survival outcome and predictors of gefitinib antitumor activity in East Asian chemonaive patients with advanced nonsmall cell lung cancer

Yang, Chih Hsin; Shih, Jin‐Yuan; Chen, Kun Chieh; Yu, Chong Jen; Yang, Tsung Ying; Lin, Ching Pei; Su, Wen; Gow, Chien‐Hung; Hsu, Chiun; Chang, Gee Chen; Yang, Pan Chyr

doi:10.1002/cncr.22220

Cited by 51 publications

(33 citation statements)

References 91 publications

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“…In general, the EGFR mutation status is well recognized as a promising predictor of a clinical efficacy to EGFR tyrosine kinase inhibitor (TKI) therapy [29][30][31][32][33] . Importantly, EGFR mutations are more common in certain subpopulations of patients with NSCLC, such as women, patients of East Asian race, patients with adenocarcinoma histology, and never-smokers [34,35] . Accordingly, the subpopulations having the abovementioned clinical backgrounds have been recognized to be more sensitive to EGFR-TKI therapy [36] .…”

Section: Discussionmentioning

confidence: 99%

Smoking History as a Predictor of Pemetrexed Monotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer

Igawa¹,

Sasaki²,

Otani³

et al. 2016

Oncology

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Background: Pemetrexed monotherapy has come to be recognized as the standard of care for second-line therapy of non-squamous non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) expression is recognized as a potential predictor of the response to pemetrexed-based chemotherapy in patients with advanced NSCLC. The purpose of this study was to identify useful predictors of the response to pemetrexed other than TS expression. Methods: The records of non-squamous NSCLC patients without driver mutations who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2009 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: In the 116 patients with non-squamous NSCLC, the overall response rate and progression-free survival (PFS) were 10.3% and 2.1 months, respectively. The disease control rate and PFS differed significantly among current smokers and never-smokers/former light smokers (44.9 vs. 65.8%, and 1.8 vs. 4.0 months, respectively). Furthermore, multivariate analysis identified Eastern Cooperative Oncology Group Performance Status and smoking status as independent predictors of the PFS. Conclusion: The clinical data obtained in this study may provide a valuable basis for the use of smoking status as a predictor of pemetrexed monotherapy in wild-type NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Smoking History as a Predictor of Pemetrexed Monotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer

Igawa¹,

Sasaki²,

Otani³

et al. 2016

Oncology

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“…The finding might be attributed to the fact that there were more females (70%) in our study. The introduction of EGFR TKI to lung cancer can improve survival after treatment in patients with certain characteristics: female, nonsmoker, histologic type of adenocarcinoma, and East Asian ethnic origin (39). Interestingly, these characteristics likewise have more frequent EGFR mutations in NSCLC (40).…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy in Lung Adenocarcinoma with Brain Metastases: Effects of Activating Epidermal Growth Factor Receptor Mutations on Clinical Response

Gow

Chien²,

Chang³

et al. 2008

Clinical Cancer Research

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130

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Purpose: Whole-brain radiation therapy (WBRT) has been applied to inoperable brain metastases in lung adenocarcinoma. Recently, an in vitro study showed reduced clonogenic survival of mutant epidermal growth factor receptor (EGFR) lung cancer cell lines in response to ionizing radiation compared with that of the wild type. To elucidate the role of EGFR mutations in radiation treatment, we evaluated the clinical response to WBRT and survival of lung adenocarcinoma patients with brain metastases. Experimental Design: This was a retrospective analysis of 63 patients with brain metastases from lung adenocarcinoma who were treated with WBRT. Demographic data, EGFR mutation status, response to WBRT, and survival data were collected. Clinical response was assessed 1 month after the start of WBRT. Univariate and logistic regression models were used to test potential predictive factors associated with clinical response. Log-rank test and Cox regression were analyzed to identify factors that affected survival. Results: Clinical response to WBRT was observed in 29 patients (46%), with 34 nonresponder patients (54%). Patients with EGFR mutations had higher response rates toWBRTcompared with those with the wild-type (54% versus 24%; P = 0.045). Both the administration of EGFR tyrosine kinase inhibitor (P = 0.034) and EGFR mutation (P = 0.029) were independently associated with response to WBRT. In Cox regression analysis, WBRT responder (P = 0.010) and absence of extracranial metastases (P = 0.002) were associated with better survival. Conclusions: Both the EGFR mutations and the administration of EGFR TKI during WBRT were independent predictors of response to WBRT in brain metastases of lung adenocarcinoma.

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“…One recent report suggests that EGFR protein overexpression contributes more strongly to TKI susceptibility than EGFR TKD mutations. 11 Although gefitinib has failed to show clinical efficacy in nonadenocarcinoma NSCLC patients, 32 other TKIs such as erlotinib or anti-EGFR antibody drugs may prove beneficial for tumors with EGFR overexpression.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities of epidermal growth factor receptor in lung squamous‐cell carcinomas, adenosquamous carcinomas, and large‐cell carcinomas

Ohtsuka

Ohnìshì

Fujiwara

et al. 2007

Cancer

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We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl‐methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d‐MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l‐MPH, and (3) will l‐MPH enantioselectively interact with ethanol to yield l‐ethylphenidate (l‐EPH)? Mice were dosed with MTS (¼ of a 12.5 cm2 patch on shaved skin) or a comparable oral dl‐MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic–mass spectrometry monitoring of N‐(S)‐prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l‐MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l‐EPH and to an elevation in d‐MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route‐dependent drug absorption rate differences, MTS was associated with significant MPH–ethanol interactions. Ethanol‐mediated increases in circulating concentrations of d‐MPH carry toxicological and abuse liability implications should this animal model hold for ethanol‐consuming attention‐deficit hyperactivity disorder patients or coabusers. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2966–2978, 2011

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Survival outcome and predictors of gefitinib antitumor activity in East Asian chemonaive patients with advanced nonsmall cell lung cancer

Cited by 51 publications

References 91 publications

Smoking History as a Predictor of Pemetrexed Monotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer

Smoking History as a Predictor of Pemetrexed Monotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer

Radiotherapy in Lung Adenocarcinoma with Brain Metastases: Effects of Activating Epidermal Growth Factor Receptor Mutations on Clinical Response

Abnormalities of epidermal growth factor receptor in lung squamous‐cell carcinomas, adenosquamous carcinomas, and large‐cell carcinomas

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