Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer.

Background: We examined how crossover therapy might affect the association between progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC).

Methods: We extracted PFS- and OS-hazard ratios (HRs) in phase III trials of molecular-targeted agents for advanced NSCLC. Their relationship was modeled in a linear function with the coefficient of determination (R-squared) to assess the correlation between PFS and OS.

Treatment-related death in patients with small-cell lung cancer in phase III trials over the last two decades.

Introduction: Treatment-related death (TRD) remains a serious problem in small-cell lung cancer (SCLC), despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time.

Role of survival post-progression in phase III trials of systemic chemotherapy in advanced non-small-cell lung cancer: a systematic review.

Background: In advanced non-small-cell lung cancer (NSCLC), with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP) has improved over the years and to what degree SPP correlates with overall survival (OS).

Methods And Findings: Median progression-free survival (MPFS) time and median survival time (MST) were extracted in phase III trials of first-line chemotherapy for advanced NSCLC.

Triplet chemotherapy with cisplatin, docetaxel, and irinotecan for patients with recurrent or refractory non-small cell lung cancer.

We examined the feasibility of triplet chemotherapy using cisplatin, docetaxel, and irinotecan for patients with recurrent or refractory non-small cell lung cancer (NSCLC), retrospectively. Twenty-five patients (21 men and 4 women) with NSCLC and good performance status who were < or = 70 years old were analyzed. The median age was 58 years.

Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results.

Background: Few studies have formally assessed whether treatment outcomes have improved substantially over the years for patients with extensive disease small-cell lung cancer (ED-SCLC) enrolled in phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials.

Methods And Findings: We searched for trials that were reported between January 1981 and August 2008.

Time to progression as a surrogate marker for overall survival in patients with advanced non-small cell lung cancer.

Purpose: With the increasing number of active compounds available for advanced non-small cell lung cancer, it is useful to evaluate whether surrogate end points can replace survival in randomized trials for the rapid and efficient assessment of efficacy. We examined the association between differences in overall survival and time to progression (TTP) using a literature survey.

Methods: We used median TTP (MTTP) and median survival time (MST) from 54 phase III trials of first-line chemotherapy involving 23,457 advanced non-small cell lung cancer patients in a multiple linear regression analysis.

Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer.

Purpose: Translational approach is essentially needed to return the achievement of basic researches to oncological practice. The molecular associations among EGFR mutation and the components of EGFR signaling pathways have been extensively studied in laboratory experiments, although were still controversial. Moreover, the impact of downstream signaling of EGFR on clinical features in patients with non-small cell lung cancer (NSCLC) remains undetermined.

Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications.

Purpose: The purpose of this study was to prospectively assess the clinical implications of neuroendocrine (NE) differentiation in non-small-cell lung cancer (NSCLC) tumors.

Methods: This study accrued subjects suspected to have lung cancer who underwent diagnostic bronchoscopy. Bronchoscopically-biopsied specimens were subjected to routine pathologic examination, and immunohistochemical studies were then performed if lung cancer was diagnosed.

Sex difference in the influence of smoking status on the responsiveness to gefitinib monotherapy in adenocarcinoma of the lung: Okayama Lung Cancer Study Group experience.

Background: Gefitinib is effective in patients with lung adenocarcinoma. Smoking status also affects the responsiveness to gefitinib, but it has not been fully evaluated whether a sex difference exists in the influence of smoking on the efficacy of gefitinib in patients with lung adenocarcinoma.

Methods: We reviewed the clinical records of 260 Japanese patients with lung adenocarcinoma who received gefitinib therapy (250 mg/day), and whose smoking status was known.

Induction of lung adenocarcinoma in transgenic mice expressing activated EGFR driven by the SP-C promoter.

To investigate the role of an activating epidermal growth factor receptor (EGFR) mutation in lung cancer, we generated transgenic mice expressing the delE748-A752 mutant version of mouse EGFR driven by the SP-C promoter, which is equivalent to the delE746-A750 mutation found in lung cancer patients. Strikingly, the mice invariably developed multifocal lung adenocarcinomas of varying sizes at between 5 and 6 weeks of age, and they died from tumor progression approximately 2 months later if left untreated. Daily oral administration of the EGFR tyrosine kinase inhibitor (TKI) gefitinib (5 mg/kg/day) reduced the total and phosphorylation levels of EGFR to those in wild-type mouse lung tissue; in addition, it abrogated tumor growth within 1 week and prolonged survival to >30 weeks.

Association of the benefit from gefitinib monotherapy with smoking status in Japanese patients with non-small-cell lung cancer.

Background: Gefitinib has been reported to be more effective in patients with non-small-cell lung cancer (NSCLC) who had low or never-smoking history than for heavier smokers. However, this has been criticized because the better survival in such subpopulation might be attributable simply to their favorable natural history, rather than any treatment effect.

Methods: We retrospectively reviewed the clinical records of 155 Japanese patients with relapsed NSCLC who received gefitinib (gefitinib-treated patients; n=83) and those who did not receive it, but were treated with other cytotoxic agents (gefitinib-untreated patients; n=72).

Remarkable shrinkage of sarcomatoid renal cell carcinoma with single-agent gemcitabine.

A 60-year-old Japanese man presented to our hospital with a painful left hip. Computed tomography showed a tumor in the left kidney and metastases in the left gluteus maximus muscle and lung. The pathological diagnosis of a biopsy specimen obtained from a metastatic lesion in the left gluteus maximus muscle was sarcomatoid renal cell carcinoma.

Impact of HER2 gene and protein status on the treatment outcome of cisplatin-based chemoradiotherapy for locally advanced non-small cell lung cancer.

Background: It has not been fully evaluated whether both HER2 gene copy number and HER2 protein expression are related to the outcome of chemoradiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC). The aim of this study was to evaluate their relationships.

Methods: HER2 gene copy number determined by fluorescence in situ hybridization (FISH) and HER2 protein expression determined by immunohistochemistry (IHC) were assessed in 68 patients with LA-NSCLC enrolled in our previous phase II trials of concurrent cisplatin-based chemoradiotherapy, and a multivariate analysis was conducted for response and survival.

Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes it unclear whether the EGFR mutation is independently associated with prolonged patient survival. In this study, we analyzed a large-scale database to discriminate the survival impact of EGFR mutations against those of sex and smoking after gefitinib therapy.

ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer.

The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients).

Elevated serum level of sialylated glycoprotein KL-6 predicts a poor prognosis in patients with non-small cell lung cancer treated with gefitinib.

Purpose: The factors affecting survival after gefitinib treatment in patients with non-small cell lung cancer (NSCLC) remain to be fully elucidated, although epidermal growth factor receptor (EGFR) mutation is a substantial prognostic factor. KL-6 has been studied as a useful indicator for interstitial lung diseases; however, it was first discovered as a lung cancer-related antigen. The aim of this study was to investigate the prognostic value of the serum KL-6 levels in advanced NSCLC patients treated with gefitinib and thus determine its association with the EGFR mutation status.

Epidermal growth factor receptor mutation status and adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung.

Purpose: Adjuvant chemotherapy with uracil-tegafur has been demonstrated to prolong survival among patients with resected lung adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations have been reported to be present in lung adenocarcinomas. The present study evaluated whether the EGFR status could be used as a biologic predictor of the outcome of adjuvant chemotherapy with uracil-tegafur.

Clinical significance of epidermal growth factor receptor gene mutations on treatment outcome after first-line cytotoxic chemotherapy in Japanese patients with non-small cell lung cancer.

Introduction: The relationship between the EGFR gene mutation status and clinical outcome has not fully been assessed in patients with non-small cell lung cancer (NSCLC) who received cytotoxic agents. The aim of this study was to clarify its association. We also examined whether this association could be affected by previous gefitinib treatment.

Role of early serial change in serum carcinoembryonic antigen levels as a predictive marker for radiological response to gefitinib in Japanese patients with non-small cell lung cancer.

Background: There have been no reports evaluating the utility of monitoring early change in serum carcinoembryonic antigen (CEA) level as a predictor for subsequent radiological response to gefitinib in patients with non-small cell lung cancer. In this report, we investigated its role using the data from 110 non-small cell lung cancer (NSCLC) patients.

Methods: The daily rate of CEA change was defined as: (M0-Mx)/Dx/M0x100(%), using the baseline level (M0), the level on day X (Mx), and the number of days from day 1 to day X (Dx).

Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer.

We previously examined the relationship between epidermal growth factor receptor (EGFR) status and clinical outcomes of nonsmall-cell lung cancer (NSCLC) patients treated with gefitinib. In our study, we additionally examined HER2 status and investigate the impact of genetic status as predictors in Japanese NSCLC patients treated with gefitinib. The HER2 copy number status was determined by fluorescence in situ hybridization assay and mutation of HER2 exon 20 was determined by direct sequencing in 74 patients to investigate the relationship between molecular statuses including HER2 and EGFR and the clinical outcomes of patients treated with gefitinib.

Relationship between response and survival in more than 50,000 patients with advanced non-small cell lung cancer treated with systemic chemotherapy in 143 phase III trials.

Background: The association between the objective response to chemotherapy and survival has not yet been fully evaluated using large cohorts in advanced non-small cell lung cancer.

Methods: We searched for phase III trials conducted between 1991 and 2006 to investigate the role of systemic chemotherapy for advanced non-small cell lung cancer. Associations were tested by multiple regression analysis.