A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer

Objectives: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC. Methods: Patients with stage III locally advanced NSCLC received paclitaxel, 50 mg/m2/week, with carboplatin area under the curve (AUC) = 2, weekly for 7 weeks, and concurrent radiotherapy, 64.8 Gy. Three dose levels of dasatinib 50, 70, and 100 mg/day were planned. Results: 11 patients with locally advanced NSCLC were entered. At the 70 mg dose level 1 patient had grade 5 pneumonitis not responsive to therapy, and one patient had reversible grade 3 pneumonitis and grade 3 pericardial effusion. Due to these toxicities the Brown University Oncology Group Data Safety Monitoring Board terminated the study. Conclusion: Dasatinib could not be safely combined with concurrent chemoradiation for stage 3 lung cancer due to pneumonitis

The Short-Term Effect of Low-Dose Radiation on Intracranial Germinoma. A Pathologic Study.

A correlative pathologic and imaging (computed tomography and magnetic resonance imaging) study is reported of a pineal germinoma in a 35-year-old man who died unexpectedly of massive pulmonary embolism on the 8th day during the course of radiation therapy after receiving a total dose of only 1600 cGy. A histologic study of the entire lesion in serial sections revealed no viable tumor cells. The tumor bed was composed of stromal elements with a variable degree of proliferation. The lymphocytic component of the tumor was unaffected by the radiation. This case provided a rare opportunity to show total eradication of tumor cells in a germinoma after a small dose of radiation and supports the notion, based on imaging observations, that histologically proven intracranial pure germinomas may be treated successfully with a much smaller dose of radiation than previously thought