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S. Kuyama
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-010 - Development of Skin Rash within the First Week Is a Potential Surrogate Marker of Effect in Afatinib for EGFR Mutant NSCLC (ID 1184)
09:30 - 17:00 | Author(s): S. Kuyama
- Abstract
Background:
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are now key agents in EGFR-mutant non-small-cell lung cancer (NSCLC). In gefitinib or erlotinib monotherapy, its efficacy could be predicted by development of skin rash, however, it has not been fully evaluated if this is similarly the case with afatinib monotherapy.
Methods:
We retrospectively studied consecutive 49 patients with EGFR-mutant NSCLC who received afatinib therapy between 2009 and 2015. Relationship with several toxicities and tumor response was examined.
Results:
Figure 1Figure 2The Grade 2 or worse common adverse events (AEs) included skin rash in 17 patients (35%), diarrhea in 19 (39%) and mucositis in 15 (31%). Of these, number of patients who developed ≥ Grade 2 AEs within the first week was 5 (10%; skin rash), 12 (25%; diarrhea) and 4 (8%; mucositis). As for objective response, 21 (43%) of the 49 had partial response. In association with AEs and antitumor effect, those who had Grade 2 or worse skin rash within the first week tended to have better tumor response as compared with those who did not have (80% vs. 39%; p = 0.077).
Conclusion:
Our small study demonstrated that early development of skin rash might predict the response to afatinib monotherapy.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-001 - Rituximab for Treatment of Lymphoma Induced Marked Regression of Malignant Mesothelioma with Dynamic Changes of Serum Cytokine Profiles (ID 1192)
09:30 - 17:00 | Author(s): S. Kuyama
- Abstract
Background:
Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. As an effective therapy remains to be established, increased attention has been given to immunotherapy in MM.
Methods:
We experienced a patient with malignant lymphoma and MM who showed marked regression of MM after the anti-CD20 monoclonal antibody rituximab therapy. Here we investigated the mechanism underlying this response by immunohistochemical staining and serum cytokine assay.
Results:
A 78-year-old man with diffuse large B-cell lymphoma and epithelioid MM was treated with rituximab for malignant lymphoma. The lymphoma responded well to rituximab, and the pleural thickening of MM regressed markedly after this treatment without therapy for mesothelioma. Immunohistochemical stainings revealed negative expression of CD20 on mesothelioma cells, indicating that rituximab did not directly attack the mesothelioma cells. The serum levels of 27 cytokines were measured 12 days before and 16, 45 and 54 days after this treatment to compare with those in 24 untreated MPM patients. The serum levels of cytokines of this patient including IL-12, INF-g, TNF-a, VEGF and IP-10 were higher than those of other mesothelioma patients before the rituximab treatment. Notably, during the treatment the level of IL-12 increased approximately 10-fold, relative to its baseline level. In addition, the levels of IL-2, Eotaxin, G-CSF, and TNF-a transiently increased several fold as compared with their baseline levels. In contrast, the levels of VEGF, PDGF, IP-10, and IL-8 which are associated with mesothelioma proliferation, decreased after the treatment. These results suggest that the mechanism of mesothelioma regression in this case involves antitumor immunity enhanced with high baseline levels of IL-12 and other Th1 cytokines and B-cell depletion by the rituximab treatment.
Conclusion:
The relationship between these cytokine profiles and the clinical outcome might provide a potential immunotherapeutic strategy for MM.
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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: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-071 - RAS Inhibitor Prevent Proteinuria of NSCLC Patients Who Received Bevasizumab Chemotherapy: NJLCG 1303 (ID 1204)
09:30 - 17:00 | Author(s): S. Kuyama
- Abstract
Background:
Proteinuria caused by bevacizumab (BV) often becomes an obstacle to continuation of the treatment. Renin-angiotensin system inhibitor (RASI), angiotensin receptor blocker and angiotensin converting enzyme inhibitor, has demonstrated anti-proteinuria effect in diabetic nephropathy and nondiabetic kidney disease. This retrospective observational study was conducted to evaluate the anti-proteinuria effect of RASI for NSCLC patients (pts) who received BV chemotherapy.
Methods:
We reviewed the medical records of NSCLC pts between 2008 and 2014 at 11 hospitals. Eligible pts had a treatment of BV chemotherapy, no proteinuria, and no diabetes mellitus. Clinical characteristics, use of the antihypertensive drugs, change of the blood pressure, and proteinuria generation were investigated during first 6 courses of BV chemotherapy.
Results:
A total of 211 pts were enrolled. Pts characteristics were: male/female 121/90; median age 63 (range 35-88); ECOG performance status 0-1/2-3 199/12; stage Ⅳ/recurrent 189/22; dose of BV(/kg) 7.5mg/15mg 21/190; BV cycle 1-2/3-4/5-6 18/55/138; antihypertensive drugs RASI/non-RASI/none 59/44/108. Proteinuria was observed in 49 pts (23%) as grade 1/2/3 33/14/2. The rate of proteinuria generation was significantly lower in the RASI group than non-RASI group (17% vs. 41%, P=0.025). Multivariate analysis revealed that RASI significantly reduced proteinuria (HR=0.43, 95% CI=0.17-0.91, P=0.043).
Conclusion:
RASI demonstrated anti-proteinuria effect for NSCLC pts who received BV therapy.
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P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.08-013 - Twenty-Four Cases of Malignant Pleural Mesothelioma in Iwakuni, Japan (ID 981)
09:30 - 17:00 | Author(s): S. Kuyama
- Abstract
Background:
Asbestos had been stopped to use in Japan since the late 1970s. Asbestos exposure will increase the risk of mesothelioma and the interval between initial exposure and subsequent biological consequences is assumed more than 40 years. Iwakuni is part of the Seto Inland Sea industrial area and one of the oldest petrochemical industrial complexes in Japan is located. The incidence of mesotheliomas is expected to rise over the next decade. Treatment for mesothelioma includes surgery, chemotherapy, radiation therapy and their combination. Recently, cisplatin in conjunction with pemetrexed has shown advantageous results in reducing tumors, but pleural mesothelioma is still incurable fatal disease except specific case. In this study, we reviewed the clinical features of 26 patients with malignant pleural mesotelioma treated in our institute.
Methods:
Between January 2006 and December 2014, 26 patients were histologically diagnosed as malignant pleural mesotelioma. Retrospective review was performed and demographic, clinical, pathologic, treatment and survival data were collected. Overall survival were estimated by the Kaplan-Meier analysis. Surgery includes two patients treated by trimodality therapy (chemotherapy + extrapleural pneumonectomy + radiation therapy) and a patient treated by pleurectomy combined with hyperthermic therapy. Other four patients were treated by extrapleural pneumonectomy alone.
Results:
In the studied population,21 of 26 patients were male.the mean age of diagnosis was 72y.Each number of histological subtypes(epithelial,sarcomatoid and biphasic) were 15,6,and 5.The number of patients who treated with surgery were 8,with chemotherapy were 17 and best supportive care was 1. The median survival time of the 27 malignant pleural mesotelioma patients was 13.4 months. According to histological subtypes,the MTS of epithelial,sarcomatoid and biphasic were 21.4 months,6.5 months and 11.6 months The MTS of surgery and chemotherapy were 21.4 months and 13.2 months.One year survival rate were 85.7% and 47.6%. The MTS of the patients with and without pleural plaque were 13.4 months and 15.0 months. Female gender, epithelial subtypes, treatment of surgery and patients without pleural plaque showed relatively favorable outcome.
Conclusion:
Because of the appearance of effecrive chemotherapies,such as Pemetrexed sodium hydrate,better survival has been observed in patients treated by chemotherapy. However, long-term survival was seen only in patients treated by surgery. Surgery allows us to accurately stage patients and provide data that may be useful in better patient stratification. Surgery should be selected for the operable patients with c-stage I-II and epithelial disease. We have to detect malignant pleural mesothelioma in early stage and treat in appropriate means.
