title: A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies.
abstract: 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.
authors.affiliation: Department of Medicine, University of Wisconsin Comprehensive Cancer Center, Madison, WI 53792, USA.
authors.forename: Afshin
authors.initials: A
authors.lastname: Forouzannia
authors.forename: Joan
authors.initials: J
authors.lastname: Schiller
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: Paul
authors.initials: P
authors.lastname: Hutson
authors.forename: David
authors.initials: D
authors.lastname: Boothman
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D019772:Topotecan