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K. Naoki
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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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P3.04-110 - PTPRH Hypomethylation as a Prognostic Factor in Non-Small Cell Lung Cancer (ID 759)
09:30 - 09:30 | Author(s): K. Naoki
- Abstract
Background:
Tyrosine phosphorylation is an important signaling mechanism in cancer. PTPRH is a receptor-type protein tyrosine phosphatase thought to be a potential regulator of tumorigenesis. The aim of this study is to clarify the significance of PTPRH expression and its regulation by DNA methylation in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma.
Methods:
PTPRH mRNA expression was examined in 89 NSCLC and corresponding non-cancerous tissues. The correlation between DNA methylation and PTPRH gene expression was investigated in another cohort that consisted of 145 patients with lung adnocarcinoma. Gene regulation by DNA methylation was assessed using a DNA methylation inhibitor. Statistic analysis was performed to clarify whether the DNA methylation status of PTPRH is a prognostic factor for patients with lung adenocarcinoma.
Results:
PTPRH mRNA expression was significantly up-regulated in NSCLC. PTPRH DNA methylation was reduced in lung ademocarcinomas and inversely correlated with mRNA expression. 5-aza-2'-deoxycytidine treatment of lung cancer cell lines with low PTPRH expression, restored mRNA PTPRH expression levels. Furthermore, low PTPRH methylation was associated with shorter recurrence-free survival (P < 0.0002) and overall survival (P < 0.0001). Multivariate analysis revealed that PTPRH DNA methylation was an independent prognostic factor (P < 0.01).
Conclusion:
We confirmed that PTPRH is overexpressed in NSCLC. In addition, we determined that hypomethylation of PTPRH is a poor prognostic factor in lung adenocarcinoma.
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P3.07 - Poster Session/ Small Cell Lung Cancer (ID 223)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.07-015 - Final Report of Phase I/II Study of Induction Carboplatin and Irinotecan Followed by TRT for Elderly Patients with LD-SCLC: TORG 0604 (ID 3232)
09:30 - 09:30 | Author(s): K. Naoki
- Abstract
Background:
In elderly patients with LD-SCLC, the role of irinotecan has been unclear and the timing of TRT combined with chemo-therapy has not been fully evaluated. Furthermore, no standard treatment has been established for them. We report a phase I/II trial of induction chemotherapy of carboplatin and irinotecan followed by sequential TRT in this population.
Methods:
Patients with untreated, measurable LD-SCLC >70 years with performance status (PS) 0 to 2 and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8 every 21 days for four cycles. TRT of 54Gy in 27 fractions was then administered sequentially. Carboplatin dose was escalated from AUC of 4 to 5 (Levels 1 and 2, respectively) with a fixed dose of irinotecan at 50 mg/m[2]. The primary objective of the phase II portion was evaluation of efficacy.
Results:
A total of 41 patients were enrolled [median age 75 years, range 70-86 years; 31 male, 10 female; PS 0/1/2: 22/18/1]. At Level 1 (n=6), one patient experienced dose-limiting toxicity (DLT) as Grade 3 hypertension. At Level 2 (n=6), two patients experienced DLT as Grade 4 thrombocytopenia. Therefore, level 1 was chosen as the recommended dose. The phase II trial was then expanded by 35 patients in the level 1 based on the Simon minimax design. In all cohorts, the median chemotherapy cycle was 4 (1/2/3/4 courses administered as 4/2/2/33); median radiation dose was 54Gy (range 36-60). Toxicities were generally mild, as expected. Gr 3/4 leukopenia and thrombocytopenia were both observed in six (15%) patients. No Gr 3/4 diarrhea or esophagitis was noted. Although Gr 3 febrile neutropenia and Gr 3 pneumonitis were seen in two patients each, no treatment-related deaths occurred. There were five complete responses and 32 partial responses, for a response rate of 90%. With median follow-up of 80.4 months (n=41), median progression-free and overall survival times were 11.2 and 27.1 months, respectively.
Conclusion:
Induction chemotherapy with carboplatin plus irinotecan followed by sequential TRT was well tolerated and highly effective in elderly patients with LD-SCLC. Further confirmatory studies are warranted.
