Significance of Thymidylate Synthase and Thyroid Transcription Factor 1 Expression in Patients with Nonsquamous Non-small Cell Lung Cancer Treated with Pemetrexed-Based Chemotherapy

Sun, Jong‐Mu; Han, Joungho; Ahn, Jin Seok; Park, Keunchil; Ahn, Myung‐Ju

doi:10.1097/jto.0b013e3182208ea8

Cited by 106 publications

(120 citation statements)

References 25 publications

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“…In these studies, several relevant parameters were not included in multivariate analyses such as site, number of metastases, type of therapy, EGFR mutation status. In a Korean study involving patients treated with pemetrexedcontaining therapy, TTF1-positive patients had better survival outcome than negative patients (Sun et al, 2011). However, OS of both cohorts of patients (25.4 versus 14.2 months, respectively) are nearly double that found in our study.…”

Section: Discussioncontrasting

confidence: 50%

“…However, several important prognostic parameters were not taken in consideration in that meta-analysis such as types of therapy, PS and EGFR status (Zhan et al, 2013). Furthermore, four studies (Barlesi et al, 2005;Martins et al, 2009;Sun et al, 2011;Chung et al, 2012) have evaluated the impact of TTF1 expression in Stage IIIB-IV NSCLC that revealed positive impact on survival. In these studies, several relevant parameters were not included in multivariate analyses such as site, number of metastases, type of therapy, EGFR mutation status.…”

Section: Discussionmentioning

confidence: 99%

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Thyroid Transcription Factor-1 Expression in Advanced Non-Small Cell Lung Cancer: Impact on Survival Outcome

Elsamany

Alfayea²,

Alzahrani³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). Materials and Methods: In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (≤60 vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. Results: A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (

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Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Thyroid Transcription Factor-1 Expression in Advanced Non-Small Cell Lung Cancer: Impact on Survival Outcome

Elsamany

Alfayea²,

Alzahrani³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…In particular, low TS mRNA, as well as reduced levels of GARFT and DHFR mRNA, significantly correlated with chemosensitivity to pemetrexed [34]. Several other studies showed that the expression of TS protein was correlated with outcome in NSCLC specimens from patients treated with pemetrexed-based chemotherapy, particularly in nonsquamous carcinomas [35,36]. The different clinical results obtained with pemetrexed in various histological subtypes of NSCLC [4] might indeed be explained with the differential TS expression, which is higher in squamous cell carcinomas than in adenocarcinomas [37].…”

Section: Pharmacogenetics Of Pemetrexedmentioning

confidence: 99%

On the pharmacogenetics of non-small cell lung cancer treatment

Santarpía

Rolfo

Peters

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

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Introduction. Despite many clinical efforts, non-small-cell lung cancer (NSCLC) has a dismal 5-year survival rate of 16%, and high incidence of recurrence. The success of biologically targeted agents, as well as the activity of well-established chemotherapeutic regimens, has been limited by inherited/ acquired resistance, and biomarkers to adapt the prescription of anticancer drugs to patients' features are urgently warranted. Areas covered. In oncology, pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best match the individual and tumor genetic profile, thus allowing maximum activity and minimal toxicity. The present review summarizes the main findings on NSCLC pharmacogenetics, critically reappraising the most important studies on polymorphisms correlated with outcome of pemetrexed and EGFR-inhibitors, and provides perspective on clinical application of genomic tests for treatment decision-making. Expert Opinion. A major challenge in NSCLC is the identification of subgroups of diseases/patients that will truly benefit from specific treatments. Ideally, convenient and minimally invasive tests to decipher biomarkers of chemosensitivity/resistance and toxicity should be developed alongside novel anticancer treatments. Integration with the latest generation of whole-genome analyses and liquid biopsies as well as prospective validation in large cohorts of patients will overcome the limitations of the traditional pharmacogenetic approaches. ARTICLE HISTORY

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“…The basic mechanism of the exceptionally favorable outcome in the current case could be putatively explained by the low TS expression in the MPM tissue, considering the previously described molecular mechanism related to pemetrexed effectiveness and resistance (5)(6)(7)(8). Given the extremely long progression-free survival, TS gene up-regulation could not have occurred in accordance with the pemetrexed treatment (8).…”

Section: Discussionmentioning

confidence: 95%

Long Progression-free Survival by Pemetrexed Continuation Maintenance Therapy Following Cisplatin-based Chemotherapy in Malignant Pleural Mesothelioma

Takeda

Itano²,

Fukita

et al. 2014

Intern. Med.

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Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. The combination of cisplatin and pemetrexed has been established as a standard chemotherapy that confers a survival benefit. Because the regimen is sometimes hampered by the renal toxicity of cisplatin and no second-line chemotherapy has yet been established, the strategy of administering a higher total dose of pemetrexed to optimize the regimen could be promising. We herein describe the case of a 69-year-old man with MPM who underwent five cycles of cisplatin plus pemetrexed and exhibited a partial response. Because his serum creatinine increased, pemetrexed maintenance therapy (PMT) was adopted, and 18 cycles were successfully delivered and the patient achieved a complete response. This case suggests that PMT could thus be useful for treating MPM.

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Significance of Thymidylate Synthase and Thyroid Transcription Factor 1 Expression in Patients with Nonsquamous Non-small Cell Lung Cancer Treated with Pemetrexed-Based Chemotherapy

Abstract: Low TS or high TTF1 protein expression was significantly associated with better clinical outcomes in nonsquamous NSCLC patients who were treated with pemetrexed-based chemotherapy. The predictive role of TS or TTF1 expression should be further validated in a prospective randomized study.

Cited by 106 publications

References 25 publications

Thyroid Transcription Factor-1 Expression in Advanced Non-Small Cell Lung Cancer: Impact on Survival Outcome

Thyroid Transcription Factor-1 Expression in Advanced Non-Small Cell Lung Cancer: Impact on Survival Outcome

On the pharmacogenetics of non-small cell lung cancer treatment

Long Progression-free Survival by Pemetrexed Continuation Maintenance Therapy Following Cisplatin-based Chemotherapy in Malignant Pleural Mesothelioma

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