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      Chemotherapy with gemcitabine plus cisplatin in patients with advanced thymic squamous cell carcinoma: Evaluation of efficacy and toxicity

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          Abstract

          Background

          Squamous cell carcinoma of the thymus is a rare thymic epithelial neoplasm that tends to widely metastasize at initial presentation. Because of its rarity, the optimal chemotherapeutic regimen remains uncertain. A gemcitabine and cisplatin regimen has shown promising efficacy in the treatment of other squamous cell carcinomas. We assessed the efficacy and toxicity of this regimen in patients with advanced thymic squamous cell carcinoma.

          Methods

          Between January 2003 and December 2012, 13 patients with untreated or unresectable recurrent thymic squamous cell carcinomas, who were treated with gemcitabine and cisplatin, were retrospectively analyzed. The endpoints in this study were clinical response rate, disease control rate, progression‐free survival, and overall survival. Significant hematological and non‐hematological toxicities were also assessed.

          Results

          Three patients were in Masaoka stage IVa and 10 were in stage IVb. The median number of treatment cycles for the present chemotherapy regimen was four. The clinical response and disease control rates were 61.5% and 92.3%, respectively. The median progression‐free and median overall survival rates were 14.5 months (95% confidence interval, 9.2–19.8 months) and 50.7 months (95% confidence interval, 24.9–76.5 months), respectively. Grade 3/4 hematological toxicities were observed in seven (53.8%) patients, and non‐hematological toxicities were mild.

          Conclusion

          This retrospective analysis demonstrated that gemcitabine plus cisplatin was active against advanced thymic squamous cell carcinoma with manageable toxicity. Gemcitabine may be a novel and alternative agent for advanced thymic squamous cell carcinoma.

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          Most cited references21

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          Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan.

          Surgery remains the mainstay of treatment for thymic epithelial tumors, and radiation and chemotherapy also have been applied widely as adjuvant and palliative procedures. We compiled records of 1,320 patients with thymic epithelial tumors who were treated from 1990 to 1994 in 115 institutes certified as special institutes for general thoracic surgery by The Japanese Association for Chest Surgery. Patients with stage I thymoma were treated with only surgery, and patients with stage II and III thymoma and thymic carcinoid underwent surgery and additional radiotherapy. Patients with stage IV thymoma and thymic carcinoma were treated with radiation or chemotherapy. The Masaoka clinical stage is an excellent predictor of the prognosis of thymoma and thymic carcinoma, but not thymic carcinoid. In stage III and IV thymoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 93%, 64%, and 36%, respectively. On the other hand, in thymic carcinoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 67%, 30%, and 24%, respectively. Prophylactic mediastinal radiotherapy could not prevent local recurrences effectively in patients with totally resected stage II and III thymoma. Adjuvant therapy including radiation or chemotherapy did not improve the prognosis in patients with totally resected III and VI thymoma and thymic carcinoma. Total resection is the most important factor in the treatment of thymic epithelial tumors. There is value in debulking surgery in invasive thymoma, but not in thymic carcinoma. We doubt that adjuvant therapy is valuable for patients with totally resected invasive thymoma and thymic carcinoma.
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            Follow-up study of thymomas with special reference to their clinical stages.

            Follow-up data were obtained for 96 cases of thymoma. The one-year survival rate was 84.3%, the three-year 77.1%, the five-year 74.1%, and the ten-year 57.1%. The five-year survival rate of total resection group was 88.9%; that of non-radically treated group was 44.4%. Clinical stages were defined: Stage I--macroscopically encapsulated and microscopically no capsular invasion; Stage II--1. macroscopic invasion into surrounding fatty tissue of mediastinal pleura, or 2. microscopic invasion into capsule; Stage III--macroscopic invasion into neighboring organ; Stage IVa--pleural or pericardial dissemination; Stage IVb--lymphogenous or hematogenous metastasis. Five-year survival rates of each clinical stage were 92.6% in Stage I, 85.7% in Stage II, 69.6% in Stage III, and 50% in Stage IV. Recurrence after total resection was found in six of 69 cases. Seven of 13 patients treated by subtotal resection survived more than five years with postoperative radiotherapy.
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              Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma.

              The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma.
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                Author and article information

                Journal
                Thorac Cancer
                Thorac Cancer
                10.1111/(ISSN)1759-7714
                TCA
                Thoracic Cancer
                John Wiley and Sons Inc. (Hoboken )
                1759-7706
                1759-7714
                04 August 2015
                March 2016
                : 7
                : 2 ( doiID: 10.1111/tca.2016.7.issue-2 )
                : 167-172
                Affiliations
                [ 1 ] Department of Medical OncologyCancer Institute/Hospital Peking Union Medical College & Chinese Academy of Medical Sciences BeijingChina
                [ 2 ] Department of PathologyCancer Institute/Hospital Peking Union Medical College & Chinese Academy of Medical Sciences BeijingChina
                Author notes
                [*] [* ] Correspondence

                Jun‐ling Li, Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.

                Tel.: +86 10 87788119

                Fax: +86 10 67734107

                Email: drlijunling@ 123456vip.163.com

                Article
                TCA12300
                10.1111/1759-7714.12300
                4773311
                27042218
                a25884e5-018f-4329-afaf-2173fe7fdb7a
                © 2015 The Authors. Thoracic Cancer published by China Lung Oncology Group and Wiley Publishing Asia Pty Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 22 May 2015
                : 29 June 2015
                Page count
                Pages: 6
                Categories
                Original Articles
                Original Article
                Custom metadata
                2.0
                tca12300
                March 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.6 mode:remove_FC converted:01.03.2016

                cisplatin,gemcitabine,squamous cell carcinoma,thymic carcinoma

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