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Emerging treatment options for patients with recurrent advanced thymic epithelial tumors.

ABSTRACT: The purpose of this review article is to review recent advances in the treatment of advanced thymic epithelial tumors. These tumors are generally responsive to cytotoxic combination chemotherapy in the first-line setting. While newer agents have shown efficacy in the salvage setting, there is no one standard approach. A multitude of targeted agents have shown promise generally in case reports, though as of yet, nothing has shown consistent benefit. Because of the rarity of thymic epithelial tumors, clinical trial enrollment is difficult but nevertheless essential.

SUBMITTER: Evans TL

PROVIDER: S-EPMC3439855 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Emerging treatment options for patients with recurrent advanced thymic epithelial tumors.

Evans Tracey L TL

OncoTargets and therapy 20120907

The purpose of this review article is to review recent advances in the treatment of advanced thymic epithelial tumors. These tumors are generally responsive to cytotoxic combination chemotherapy in the first-line setting. While newer agents have shown efficacy in the salvage setting, there is no one standard approach. A multitude of targeted agents have shown promise generally in case reports, though as of yet, nothing has shown consistent benefit. Because of the rarity of thymic epithelial tumo ...[more]

PMID: 22973113

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Project description:BackgroundHere, we investigated radiological responses following chemotherapy alone as compared to both radiation/chemotherapy (chemoRT) in patients with thymic epithelial tumors (TETs) who did not receive upfront surgery.MethodsTETs treated at a tertiary academic cancer center between January 2007 and July 2018 were identified. Patients received chemotherapy or chemoRT as initial therapy and pre- and post-treatment scans were available. Student's t-test, Wilcoxon rank-sum tests, and Cox proportional hazards method were used to compare clinical details and survival between groups. The primary outcome was change in tumor size, which was compared between groups using linear mixed-effects regression models, adjusting for baseline tumor size, age, and histology.ResultsA total of 24 of 114 patients with TETs identified met the inclusion criteria. The majority of patients had 67% thymoma (67%, n = 16) and AJCC8 III-IVA disease (58%, n = 14). Median age was 58.5 years (range: 33-76), median initial tumor volume was 187.1 cc (range: 28.7-653.6) and diameter was 8.5 cm (range: 4.5-14.3). Half of the patients received upfront chemotherapy (n = 12: 83% cisplatin/adriamycin/cyclophosphamide) or chemoRT (n = 12: 58% carboplatin/paclitaxel; median RT dose: 63 Gy [range: 60-70 Gy]). At a median imaging follow-up of 15 months (range: 0-86): ChemoRT was associated with increased average radiological response compared to chemotherapy alone (volume: -47.0 cc more, P < 0.001; diameter: -0.8 cm more, P = 0.03). In eight patients who received chemotherapy, 33% saw further tumor shrinkage (median volume: -42.3%, P = 0.03; diameter: -3.0%, P = 0.049) with additional radiation/chemoradiation. Median survival increased for patients ultimately receiving surgery versus those who did not (46 month, range: 16-127 vs. 14 month, range: 6-82; P < 0.01).ConclusionsChemoRT produced a greater radiologic response compared to chemotherapy alone in patients with TETs not suitable for upfront resection.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: We found that chemoRT was associated with a greater radiologic response compared to patients who received chemotherapy alone.What this study addsWhat this study adds: In patients with TET not amenable to upfront resection, chemoRT may be a feasible strategy for cytoreduction.

Project description:BACKGROUND:No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy. METHODS:Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with ClinicalTrials.gov, number NCT00965250. FINDINGS:49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24·0 months (IQR 17·3-36·9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3-4 adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune conditions during treatment (five were new-onset disorders), the most common of which was pure red-cell aplasia. Two (4%) patients died; one was attributed to disease progression and the other to disease-related complications (respiratory failure, myositis, and an acute coronary event), which could have been precipitated by treatment with cixutumumab. INTERPRETATION:Cixutumumab monotherapy is well-tolerated and active in relapsed thymoma. Development of autoimmunity during treatment needs further investigation. FUNDING:Division of Cancer Treatment and Diagnosis at the National Cancer Institute (National Institutes of Health), ImClone Systems.

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Emerging treatment options for patients with recurrent advanced thymic epithelial tumors.

Publications

Emerging treatment options for patients with recurrent advanced thymic epithelial tumors.

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