TY - JOUR
T1 - A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies
AU - Forouzannia, Afshin
AU - Schiller, Joan
AU - Berlin, Jordan
AU - Hutson, Paul
AU - Boothman, David
AU - Storer, Barry
AU - Wilding, George
AU - Mehta, Minesh
N1 - Funding Information:
We thank Dona Alberti, BSN, RN; Rhoda Arzoomanian, BSN, RN; Kimberly Binger, BSN, RN; Christine Feierabend, BSN, RN; Jennifer Kavka, BS; Nancy Kehrli, M.S.; and Marcy Pomplun, B.S. This study was supported by NCI U01 CA62491.
PY - 2004/4
Y1 - 2004/4
N2 - 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 60Gy 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 0.5mg/m2 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 0.4mg/m2 per day, based on dose limiting toxicities (DLTs) observed at 0.5mg/m2 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 0.4mg/m2 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.
AB - 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 60Gy 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 0.5mg/m2 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 0.4mg/m2 per day, based on dose limiting toxicities (DLTs) observed at 0.5mg/m2 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 0.4mg/m2 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.
KW - Lung cancer
KW - Phase I
KW - Radiosensitizers
KW - Topotecan
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U2 - 10.1016/j.lungcan.2003.10.005
DO - 10.1016/j.lungcan.2003.10.005
M3 - Article
C2 - 15013589
AN - SCOPUS:1542358164
SN - 0169-5002
VL - 44
SP - 111
EP - 119
JO - Lung Cancer
JF - Lung Cancer
IS - 1
ER -