Incremental low doses of amrubicin for the treatment of bone marrow metastasis in small cell lung cancer

Lung cancer remains the leading cause of cancer death, and approximately 13% of all patients with lung cancer are diagnosed as having small cell lung cancer (SCLC). Although SCLC is highly sensitive to first-line chemotherapy and radiation therapy, most SCLC patients experience relapse within two years and die from systemic metastasis. Despite the fact that bone marrow is well known to be one of the organs affected by metastasis, (4) there is no established treatment for bone marrow metastasis of SCLC. To our knowledge, this is the first case report of extensive disease SCLC (ED-SCLC) and bone marrow metastasis successfully treated with low-dose amrubicin alone. A 71-year-old male patient presenting with a one-week history of general fatigue and eventual disorientation was referred to us. Laboratory tests revealed hyponatremia (104 mEq/L) and pancytopenia (white blood cells, 1,900/µL; hemoglobin, 8.0 g/dL; and platelet count, 1.9 µg/mL). In addition, there was an abnormal shadow with multiple swollen lymph nodes on chest X-ray and CT scans (Figure 1). Bone marrow aspiration revealed bone marrow metastasis of SCLC (Figure 2). He was diagnosed with ED-SCLC (tumor-node-metastasis staging system cT4N3M1, stage IV) and bone marrow metastasis. Enhanced magnetic resonance imaging of the brain showed no evidence of brain metastasis. Treatment was started with a low dose (30 mg/m 2) of amrubicin and platelet transfusion (100,000 units). His pancytopenia and disorientation improved after two courses of amrubicin. We administered escalating doses (from 30 to 35 mg/m 2) of amrubicin based on the performance status of the patient. A total of six courses of amrubicin were administered (two and four cycles of 30 mg/m 2 and 35 mg/m 2 , respectively), resulting in complete response, as determined by Response Evaluation Criteria in Solid Tumors. After a six-month follow-up period, the SCLC remained in complete remission. Amrubicin is a fully synthetic 9-aminoanthracycline, which is converted in the body to amrubicinol by reduction of the ketone in position 13. Amrubicinol has a higher antitumor activity than does the parent molecule. Although they are classified as anthracycline agents, amrubicin and amrubicinol exert cytotoxic effects as DNA topoisomerase II inhibitors rather than as DNA intercalators. In Japan, a phase II study showed the results of intravenous administration of single-agent amrubicin at 40 mg/m 2 for three consecutive days in previously treated SCLC patients. The overall response rates were 52% and 50% in cases of sensitive SCLC and refractory/relapsed SCLC, respectively, and the …