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MO03 - Thymic Malignancies (ID 123)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:F. Detterbeck, M. Okumura
- Coordinates: 10/28/2013, 10:30 - 12:00, Bayside Gallery B, Level 1
MO03.10 - A multicenter prospective study of carboplatin and paclitaxel for advanced thymic carcinoma: West Japan Oncology Group 4207L (ID 987)
10:30 - 12:00 | Author(s): J. Fukuoka
Thymic carcinoma (TC) is a rare malignant tumor originated within the thymus gland and is associated with a poor prognosis, differing from thymoma which is the most common type of thymic malignant neoplasm. No results of clinical trials focusing on TC have been reported. This single-arm study evaluated carboplatin and paclitaxel (CbP) in previously untreated patients (pts) with advanced TC.
Pts with Masaoka’s stage III to IVb TC, ECOG PS 0 to 1, and more than 20 years old were eligible. The study treatment consisted of carboplatin (AUC 6) and paclitaxel (200 mg/m2) every 3 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) by extramural assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. All pts were followed-up until 24 months (mo) after last enrollment. Based on the SWOG 2-stage design, the planned sample size of 40 pts was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05.
From May 2008 to November 2010, 40 pts were enrolled from 21 centers. Of 39 evaluable for analysis, the median age was 62 years (range, 36–84); 23/16 males/females; 3/10/26 with Masaoka’s stage III/IVa/IVb; 9/11/19 with squamous cell carcinoma/poorly differentiated neuroendocrine carcinoma/other types. The median number of cycles was 6. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval [CI], 21-53%; P = 0.031). The median PFS was 7.5 mo (6.2-12.3 mo) while OS did not reach the median value. The 1-year and 2-year survival rates were 85% (95% CI, 69-93%) and 71% (95% CI, 54-83%), respectively. Major adverse event was grade 3-4 neutropenia in 34 pts (87%). Two cases (5%) of grade 3 febrile neutropenia, neuropathy, and arthralgia were observed, respectively. There was no treatment-related death.
CbP showed high efficacy in advanced TC. Our results established that CbP, one of the standard treatments for non-small cell lung cancer, also serves as a key chemotherapy regimen for TC.
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P1.01 - Poster Session 1 - Cancer Biology (ID 143)
- Event: WCLC 2013
- Type: Poster Session
- Track: Biology
- Presentations: 1
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
P1.01-023 - The expression of ATBF1 is inversely proportion to the expression of estrogen receptor in lung cancer cells (ID 2668)
09:30 - 16:30 | Author(s): J. Fukuoka
Sex difference is an important factor to differentiate the clinical characteristics of lung cancers. Sex hormones derived signaling should be involved in the etiology of lung cancers. The most important factor may be estrogen that is suspected carcinogen, since strong epidemiological evidence associates the hormone to breast, endometrial, and uterine cancers. We have been studied the involvement of ATBF1 that is a large transcription factor playing an important role as a tumor suppressor in various cancers. Intriguing fact is that estrogen at lower levels increases the expression of ATBF1, but at higher levels decreases ATBF1. The response of ATBF1 is explained by the negative feedback through the estrogen-responsive proteasome system. This is the first study to reveal the expression of ATBF1 in lung cancers and explain the clinical characteristic of lung cancer differentiated by sex.
We prepared a cell line array from 17 lung cancer cell lines, which was consisted of twelve adenocarcinomas, three squamous cell carcinomas, one large cell carcinoma and one undifferentiated cancer. We generated five antibodies against ATBF1 (MB34-2, MB39-1, D1-120, MB44-2, MB47-2) at distinct part of the protein from N-terminal to C-terminal. We also analyzed the expression of p53, p21, ATM, psATM, estrogen receptors (ER), progesterone receptor (PR) , thyroid transcription factor 1 (TTF-1) and CEA by immunohistochemical analysis. The intensity of each factor was graded (score: 0-3) from weak expression (score: 0) to strong expression (score: 3). The intensity was scored in comparison with the intensity of ATB1 for other factors.
Positive rates of ATBF1 with each antibody (MB34-2, MB39-1, D1-120, MB44-2, MB47-2) were 88%, 100%, 100%, 76% and 71%. Positive rates of p53, p21, ATM, psATM, ER, PR, TTF-1 and CEA were 53%, 41%, 47%, 41%, 65%, 42%, 29% and 76%, respectively. There was no significant difference in the expression pattern of each factor between adenocarcinoma and squamous cell carcinoma but TTF-1. We divided lung cancer cells into two groups by expression pattern of ATBF1. Wide range expression (W) group is characterized by the positive expression with all antibody whereas the limited expression (L) group that is characterized by limited number of positive with these antibodies. The expression rate of ER was significantly low in W group (45%, 5/11) in contrast to L group (100%, 6/6) (p=0.025).
The higher expression of ER, the lower and limited expression of ATBF1. The observation may be relevant to the breaking down mechanism of ATBF1 through estrogen-ER signaling discovered in breast cancer. The protein stability of ATBF1 should be an important factor for the prognosis of lung cancer distinguished by the sex.