amrubicin and Thymus-Neoplasms

There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor.. This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1-3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients.. A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%-32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient.. Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

Topics: Anthracyclines; Antineoplastic Agents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Non-Randomized Controlled Trials as Topic; Patient Selection; Prognosis; Prospective Studies; Salvage Therapy; Survival Rate; Thymoma; Thymus Neoplasms

There has been no standard chemotherapy for advanced or recurrent thymic malignancies including thymic carcinoma (TC) and invasive thymoma (IT), though platinum and anthracycline have been reported as effective agents for the treatment of these diseases. The objective of this study was to evaluate the efficacy and safety of the combination of amrubicin (AMR), a new anthracycline agent, and carboplatin (CBDCA) in patients with advanced thymic malignancies.. Patients with histologically confirmed thymic malignancies received AMR (35 mg/m, days 1-3) and CBDCA (area under the curve 4.0, day 1) every 3 weeks. Patients who had received previous chemotherapy were treated with a reduced dose of AMR (30 mg/m). The primary end point was objective response rate (ORR), and secondary endpoints were progression-free survival, overall survival, and toxicity profile.. From December 2008 to October 2012, 51 patients (33 TC and 18 IT) were enrolled. The median number of treatment cycles was four in each group. The ORR and progression-free survival were 30% (95% confidence interval, 14-46) and 7.6 months in the TC group, and 17% (95% confidence interval, 0-34) and 7.6 months in the IT group, respectively. The ORR of TC patients without previous chemotherapy (n = 19) was 42%. Although grade 3 or 4 hematological toxicities were common including neutropenia (82%) and febrile neutropenia (22%), these were transient and manageable. Nonhematological toxicities were moderate and no treatment-related death was observed.. The combination of AMR with CBDCA was active for TC with acceptable toxicity, although it was not effective for IT. Further investigation of this regimen for advanced TC is warranted.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Female; Humans; Japan; Male; Middle Aged; Thymoma; Thymus Neoplasms

Anthracycline-based regimens with cisplatin have been commonly used for inoperable and relapsed thymoma. However, little information is available regarding the usefulness of salvage chemotherapy. Here, we describe a case of invasive thymoma associated with myasthenia gravis that showed a marked response to third-line chemotherapy, with single-agent amrubicin, a synthetic anthracycline analog and potent deoxyribonucleic acid topoisomerase II inhibitor. Amrubicin appears to have significant activity against invasive thymoma.

Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Female; Humans; Myasthenia Gravis; Salvage Therapy; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

Thymic carcinoma is a rare mediastinal neoplasm, and the prognosis of patients with advanced thymic carcinoma is poor. No standard chemotherapeutic regimen has yet been established for the disease. This is the first report to evaluate the role of amrubicin, a novel anthracycline anticancer drug, in second-line and beyond treatment for patients with platinum-refractory advanced thymic carcinoma.. This study was a review of thymic carcinoma patients who had received amrubicin monotherapy between June 2003 and December 2011 for the progression of disease previously treated with platinum-based chemotherapy. Amrubicin was administered at 35 or 40 mg/m(2) for three consecutive days every 3 weeks, until progression.. Nine patients with recurrent thymic carcinoma were registered. Their median age was 61 years (range 45-72), and the patients included five males and four females. All nine patients had Masaoka's Stage IVb disease. There were three squamous cell carcinomas, one adenocarcinoma, one small-cell carcinoma and two other histological types. The mean number of chemotherapy cycles was five (range 2-13). Grade 3 or higher toxicities included mainly neutropenia (55.5%), anemia (25.0%) and febrile neutropenia (11.1%). No treatment-related deaths were observed. The response rate was 44.4% (95% confidence interval: 19-73). The median progression-free survival after the amrubicin monotherapy was 4.9 months, while the median overall survival was 6.4 months.. Single-agent amrubicin was found to be potentially useful as second-line and beyond chemotherapy for patients with advanced thymic carcinoma. Further multi-institutional prospective studies are warranted.

Topics: Adenocarcinoma; Aged; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Platinum Compounds; Retrospective Studies; Thymoma; Thymus Neoplasms; Treatment Outcome

Topics: Anthracyclines; Antineoplastic Agents; Carcinoma, Small Cell; Humans; Lung Neoplasms; Male; Middle Aged; Pleural Neoplasms; Salvage Therapy; Thymus Neoplasms