A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 44; no. 1; pp. 111 - 119
• Main Authors: Forouzannia, Afshin, Schiller, Joan, Berlin, Jordan, Hutson, Paul, Boothman, David, Storer, Barry, Wilding, George, Mehta, Minesh
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.04.2004; Elsevier Science
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacology; Biological and medical sciences; Combined Modality Therapy; Diarrhea - chemically induced; Esophagitis - chemically induced; Female; Humans; Lung cancer; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Neutropenia - chemically induced; Phase I; Pneumology; Radiation-Sensitizing Agents - administration & dosage; Radiation-Sensitizing Agents - adverse effects; Radiation-Sensitizing Agents - pharmacology; Radiosensitizers; Thoracic Neoplasms - drug therapy; Thoracic Neoplasms - pathology; Thoracic Neoplasms - radiotherapy; Thrombocytopenia - chemically induced; Topotecan; Topotecan - administration & dosage; Topotecan - adverse effects; Topotecan - pharmacology; Treatment Outcome; Tumors of the respiratory system and mediastinum; Radiosensitizers; Topotecan; Phase I; Lung cancer; Lung disease; Respiratory disease; Phase I trial; Bronchus disease; Malignancy; Thorax; Malignant tumor; Bronchopulmonary malignant tumor
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2003.10.005

Purpose: To determine the maximum-tolerated dose (MTD) of daily Topotecan with full-dose thoracic radiotherapy (XRT). Methods and materials: Patients with advanced thoracic malignancies requiring full dose radiation received daily I.V. Topotecan prior to each daily session of XRT to 60 Gy over 6 weeks. Dose levels (and subjects studied at each) have been 0.2 ( N=7), 0.3 ( N=5), 0.4 ( N=7), and 0.5 mg/m 2 per day ( N=5) in a best-of-five design. Tumor response was assessed at 4–8 weeks after completion of therapy. Results: From March 1995 to December 1999, a total of 24 patients were treated. The MTD of Topotecan was 0.4 mg/m 2 per day, based on dose limiting toxicities (DLTs) observed at 0.5 mg/m 2 per day, which were grade 4 hematological toxicities or diarrhea and grade 3 esophagitis. Tumor responses included: zero complete response (CR), nine partial responses (PR), five stable disease (SD), nine progressive disease (PD) and one not evaluated (NE). Additionally, local response was also assessed separately (within the XRT ports) and there were 10 PR, 12 SD, 1 PD, and 1 NE. Conclusion: the MTD of Topotecan with concomitant thoracic radiotherapy is 0.4 mg/m 2 per day. The DLTs observed were grade 4 diarrhea, grade 3 esophagitis and grade 4 hematological toxicities. Based on the known radiosensitizing effect of Topotecan, this dose is recommended for phase II testing.