A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies.
OBJECTIVE
To determine the maximum-tolerated dose (MTD) of daily Topotecan with full-dose thoracic radiotherapy (XRT).


METHODS
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 0.5mg/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.


CONCLUSIONS
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.
Forouzannia
Afshin
A
Department of Medicine, University of Wisconsin Comprehensive Cancer Center, Madison, WI 53792, USA.
Schiller
Joan
J
Berlin
Jordan
J
Hutson
Paul
P
Boothman
David
D
Storer
Barry
B
Wilding
George
G
Mehta
Minesh
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000139:chemically induced; D004941:Esophagitis / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D013899:Thoracic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D019772:Topotecan