A Refractory Stage IVb Thymoma Responded Completely to a Combination of Dasatinib and Prednisone but Poorly to Either One Alone

Thymomas are rare tumors for which there is little randomized evidence to guide treatment and therefore, therapeutic options to cure advanced malignant thymomas are limited. We hereby report the first clinical outcome of combined dasatinib and prednisone therapy in a patient with heavily treated stage IVB malignant thymoma.

A 41 year old white male presented with fatigue, fever and granulocytopenia. He soon developed myasthenia gravis and aplastic anemia. Computer tomography showed a mediastinal mass, pleural thickening, splenomegaly and mesenteric nodes; biopsy of mediastinal mass revealed a malignant thymoma. Prednisone for 6 weeks along with antithymocyte globulin and cyclosporine were started for myasthenia gravis and aplastic anemia. Chemotherapy for unresectable thymoma was soon initiated with ADOC (Cisplatin, Doxorubicin, Vincristine, and Cyclophosphamide), but only small partial response was noted. After failing to show response to another three lines of therapy, we commenced therapy with dasatinib 75 mg twice daily. Thymoma showed partial response to dasatinib initially but soon became resistant and progressed. When prednisone 100 mg daily was added, a complete response was observed.

A patient with stage IVB thymic carcinoma failed to respond well 3 lines of combination chemotherapy, and neither to prednisone or dasatinib alone. When dasatinib is combined with prednisone, it induced a complete response.

Off Label Use: Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor. It is a potent inhibitor of Imatinib resistant KIT activation loop mutants and induces apoptosis in mast cells and leukemic cells. At higher concentrations, Dasatinib also inhibits c-Kit, PDGFR and EphedrinA2. it has currently FDA approval for treatment of adults in all phases of chronic myeloid leukemias with resistance or intolerance to prior therapy, including Gleevec. The second indication for Dasatinib, is for the treatment of Ph+ALL. A number of Phase II trials have shown activity of this agent to various solid tumors including breast and lung cancer. Imatinib showed activity in thymomas, thus the rationale for using Dasatinib in the treatment of our patient.