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K. Shimizu
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-007 - Evaluation of Gefitinib Efficacy According to Body Surface Area, Body Weight, and Body Mass Index in Patients with NSCLC Harboring EGFR Mutations (ID 1681)
09:30 - 09:30 | Author(s): K. Shimizu
- Abstract
Background:
Gefitinib is effective as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive epidermal growth factor receptor (EGFR) mutations. Exon 19 deletions and the L858R point mutation are the most commonly encountered sensitive EGFR mutations in NSCLC, and have been shown to predict greater efficacy of gefitinib therapy. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect the efficacy of gefitinib in patients with NSCLC harboring sensitive EGFR mutations.
Methods:
We reviewed the medical charts of consecutive patients with advanced NSCLC harboring sensitive EGFR mutations who received gefitinib. The median values were used as the cutoffs to evaluate the impact of BSA and BW on the efficacy of gefitinib. BMI was categorized as underweight (BMI < 18.5 kg/m[2]), normal weight (BMI 18.5 to < 25 kg/m[2]), and overweight (BMI ≥ 25 kg/m[2]).
Results:
The median BSA and BW of the 138 NSCLC patients harboring sensitive EGFR mutations were 1.48 m[2] and 53 kg, respectively. The overall response rate, progression-free survival (PFS), and overall survival (OS) were 65.2%, 12.2 months, and 24.2 months, respectively. There were no significant differences in clinical outcomes between the high-BSA (BSA ≥ 1.43 m[2]) and low-BSA groups (BSA < 1.43 m[2]), with response rates of 68.5% and 72.0% (p = 0.92), median PFS of 12.2 and 11.5 months (p = 0.73), and median OS of 25.0 and 21.9 months, respectively (p = 0.28). Moreover, there were no significant differences in clinical outcomes between the high-BW (BW ≥ 53 kg) and low-BW groups (BW < 53 kg), with response rates of 63.3% and 67.1% (p = 0.72), median PFS of 12.2 and 10.8 months (p = 0.46), and median OS of 28.9 and 21.9 months, respectively (p = 0.22). For BMI, the median PFS and OS estimated among underweight, normal weight, and overweight patients were 10.6 and 19.2 months, 12.0 and 23.3 months, and 13.1 and 33.1 months, respectively. There were no statistically significant differences in PFS and OS among underweight, normal weight, and overweight patients (p = 0.52 and p = 0.30, respectively). Finally, to substantiate possible differences in the efficacy in patients who are young (<75 years) vs. elderly (≥ 75 years) and who have exon 19 deletions vs. L858R, we also evaluated these subgroups separately regarding BSA, BW, and BMI. However, there were no significant differences in the PFS and OS between these groups.
Conclusion:
The efficacy of gefitinib in patients with NSCLC harboring sensitive EGFR mutations does not differ according to their BSA, BW, and BMI.
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P3.01-012 - Efficacy of Chemotherapy after First-Line Gefitinib for EGFR-Mutant NSCLC Patients (ID 762)
09:30 - 09:30 | Author(s): K. Shimizu
- Abstract
Background:
Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations.
Methods:
We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at 5 institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy.
Results:
Between January 2006 and December 2012, 42 patients (8 men, 34 women; median age, 63 years [range, 39–75 years]) were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2%, 61.9%, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0%, 95.2%, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was indpendently associated with improved PFS.
Conclusion:
Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-101 - Expression of the Endoplasmic Reticulum Stress Sensor BiP/GRP78 in Lung Adenocarcinoma: Correlations and Prognostic Significance (ID 2271)
09:30 - 09:30 | Author(s): K. Shimizu
- Abstract
Background:
Endoplasmic Reticulum (ER) Stress Sensor, BiP/glucose-related protein 78 (GRP78) is an important member of the heat shock protein family 70 (HSPs70) that plays an essential role in the tumor growth and progression. It is localized to the endoplasmic reticulum. Although GRP78/BiP is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear. The aim of the present study was to investigate the expression of the GRP78/BiP in patients with lung adenocarcinoma.
Methods:
Two hundred and twenty patients with surgically resected lung adenocarcinoma were evaluated as one institutional cohort. Tumor sections were stained by immunohistochemistry for GRP78/BiP, PERK, Ki-67, p-mTOR, and CD34 to assess the microvessel density. The correlation between GRP78/BiP and the other factors was assessed using the Spearman correlation analysis.
Results:
GRP78/BiP was highly expressed in 41% of patients, and was significantly associated with pleural invasion, lymphatic permeation, vascular invasion, cell proliferation, and p-mTOR phosphorylation. Multivaritate analysis confirmed that GRP78/BiP expression was an independent factor for predicting poor progression-free survival and overall survival in patients with stage I disease.
Conclusion:
The increased GRP78/BiP expression is an independent prognostic factor for early stage lung adenocarcinoma patients. Our study suggests that the expression of GRP78/BiP as ER stress marker plays a crucial role in the pathogenesis and development of lung adenocarcinoma.
