title: Phase I/II clinical study of pulsed paclitaxel radiosensitization for thoracic malignancy: a therapeutic approach on the basis of preclinical research of human cancer cell lines.
abstract: OBJECTIVE
  A Phase I/II clinical study using pulsed low-dose paclitaxel and radiation for thoracic malignancy was conducted. The study was based on preclinical research of the effects of paclitaxel on apoptosis and the cell cycle in human cancer cell lines.
  
  
  METHODS
  Three human epithelial cancer cell lines were investigated for preclinical study. Cells were analyzed for apoptosis and cell cycle characteristics after paclitaxel treatment. The Phase I/II clinical trial for non-small cell lung cancer used pulsed low-dose paclitaxel three times/week with the starting dose of 15 mg/m(2). Daily thoracic radiotherapy was delivered in 1.8 Gy/fraction to 60-65 Gy for gross disease and to 45-58 Gy for microscopic disease. Timing of radiotherapy was delayed to allow for a minimum of 4 h for cell cycle progression.
  
  
  RESULTS
  Forty-one patients have enrolled and 33 completed treatments. Seventeen patients completed the Phase I study, with an average primary tumor shrinkage of 83 +/- 8% (95% confidence interval). Tumor response rate was 100% for the Phase I study. Overall local control was 98%, and the survival rate was 46% at 1 year, 33% at 2 years, and 18% at 3 years. Toxicity was low with 3 of 18 patients having grade 3 pneumonitis and 3 of 18 patients having grade 3 esophagitis. There was no grade 4 pneumonitis, esophagitis, or hematological toxicity.
  
  
  CONCLUSIONS
  Pulsed low-dose paclitaxel radiosensitization for non-small cell lung cancer resulted in a superior local control rate and comparable survival rate when compared with chemoradiation regimens using systemic dose chemotherapy. The regimen is associated with low toxicity and deserves additional investigation, particularly in patients with poor performance or older age, who cannot tolerate standard chemoradiation regimens.
authors.affiliation: Department of Radiation, James P. Wilmot Cancer Center, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA. yuhchyau_chen@urmc.rochester.edu
authors.forename: Yuhchyau
authors.initials: Y
authors.lastname: Chen
authors.forename: Kishan
authors.initials: K
authors.lastname: Pandya
authors.forename: Peter C
authors.initials: PC
authors.lastname: Keng
authors.forename: David
authors.initials: D
authors.lastname: Johnstone
authors.forename: Jigang
authors.initials: J
authors.lastname: Li
authors.forename: Yi-Jang
authors.initials: YJ
authors.lastname: Lee
authors.forename: Therese
authors.initials: T
authors.lastname: Smudzin
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020714:Maximum Tolerated Dose; D008938:Mitosis / Q000187:drug effects; D017239:Paclitaxel / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013899:Thoracic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014407:Tumor Cells, Cultured
chemical_list: D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel