Phase II Study of Carboplatin and Paclitaxel in Advanced Thymoma and Thymic Carcinoma

Article (PDF Available)inJournal of Clinical Oncology 29(15):2060-5 · May 2011with55 Reads
DOI: 10.1200/JCO.2010.32.9607 · Source: PubMed
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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Available from: Corey Langer, Jun 20, 2015
    • "As first-line chemotherapy for advanced thymic carcinoma, cisplatin and anthracycline-based chemotherapies, such as ADOC (9) and the combination of cisplatin, Adriamycin and cyclophosphamide (10), are applied in the clinical setting based on Einhorn’s protocol for germ cell tumors. Only a prospective phase II trial with carboplatin and paclitaxel for unresectable stages has been performed, indicating the efficacy of platinum-based doublet chemotherapy (11). With regard to second-line chemotherapies, evidence for efficacious regimens has not been presented and almost all reported series have included only small numbers of patients (12). "
    [Show abstract] [Hide abstract] ABSTRACT: Thymic carcinoma is a rare cancer that is more aggressive and shows a poorer prognosis compared with thymoma. Molecular analysis has demonstrated that this entity is clearly distinct from thymoma. However, no definitive clinical management has been reported, and the roles of chemotherapy and radiotherapy for advanced thymic carcinoma remain unclear given the rarity of this clinicopathology. The current study reports the case of a 65yearold male who presented with advanced thymic carcinoma with solitary brain and pulmonary metastases, but demonstrated longterm survival following multiple lines of chemotherapy and radiotherapy with palliative intent. Although the solitary brain metastasis was well controlled for several years using wholebrain irradiation, cognitive function gradually declined with cerebral atrophy. Thymic carcinoma is known to show a poor prognosis and aggressive clinical progress, however, it occasionally demonstrates a clinically indolent course. Modalities of treatment should thus be selected prudently to avoid toxicity, in consideration of the possibility of longterm survival. Stereotactic radiation therapy for brain metastases, including cyberknife or γknife surgery, appears to represent the optimal local treatment for such patients with unexpectedly longer survival due to indolent thymic carcinoma.
    Full-text · Article · Jun 2014
    NagamataNagamataOkumaOkumaYamadaYamada+1 more author ...HishimaHishima
    • "Median survival time was 20.0 months for patients with TC, but it has not been reached for patients with thymoma. Therefore, the authors concluded that carboplatin and paclitaxel and other regimens without anthracyclines , led an ORR consistently lower than those regimens containing anthracyclines [46]. On the other hand, a recent a single-arm study was performed evaluating carboplatin and paclitaxel in previously untreated patients with advanced TC; data showed an ORR of 36% and a median PFS of 8.1 month, suggesting this one could be a key chemotherapy regimens for TC [47] . "
    [Show abstract] [Hide abstract] ABSTRACT: Thymic malignancies represent a wide range of clinical, histological and molecular entities, with probably considerable heterogeneity even among tumors of the same histotype. Systemic chemotherapy with cisplatin-based regimens continues to represent the standard of care in metastatic or inoperable refractory/recurrent diseases and ADOC regimen (including cisplatin, doxorubicin, vincristine and cyclophosphamide) demonstrated the longer overall response rate and median survival in the first line setting, although no randomized trial is available; and there is still a lack of standard treatment after first-line failure. To date research efforts are focused on translational studies on molecular pathways involved in thymic tumors carcinogenesis, aimed to better understand and predict the efficacy of chemotherapy and targeted therapy. Recent molecular characterization includes identification of a number of oncogenes, tumor suppressor genes, chromosomal aberrations, angiogenic factors, and tumor invasion factors involved in cellular survival and proliferation and in tumor growth. The use of biologic drugs is currently not recommended in a routine practice because there are limited data on their therapeutic role in thymic epitelial tumors. Because of the lack of data from adequate-sized, prospective trials are required for validation and the enrolment of patients with advanced disease into available clinical trials has to be encouraged.
    Full-text · Article · Nov 2013
    • "The extent of disease at presentation often precludes complete surgical resection, and systemic chemotherapy plays a very important role in treatment. Because of its rare occurrence, only small numbers of cases have been analyzed in previous studies published thus far [4, 5, 6, 7]. The optimal chemotherapy regimen for thymic carcinoma remains unclear. "
    [Show abstract] [Hide abstract] ABSTRACT: Thymic carcinoma is a rare but aggressive neoplasm. Although there is no clearly optimal first- or second-line chemotherapy regimen for thymic carcinoma, platinum-based chemotherapy has repeatedly been shown to be of benefit to patients with advanced thymic carcinoma. Some case reports have described S-1 as a novel agent with good activity against advanced thymic carcinoma. A 74-year-old female was diagnosed with thymic carcinoma complicated by pleural dissemination and pericardial effusion of carcinomatosa. She was treated with carboplatin on day 1 plus S-1 on days 1-14 in cycles repeated every 3 or 4 weeks. Four cycles of this regimen were administered, and a partial response was confirmed. There were no severe hematological or nonhematological toxicities, and no dose reduction was necessary. To our knowledge, this is the first report to demonstrate the efficacy of combination chemotherapy consisting of carboplatin and S-1 against thymic carcinoma.
    Full-text · Article · Oct 2013
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