title: A phase I study of concurrent 9-nitro-20(s)-camptothecin (9NC/Orathecin) and radiation therapy in the treatment of locally advanced adenocarcinoma of the pancreas.
abstract: OBJECTIVE
  In vitro studies have suggested that 9-nitro-20(s)-Camptothecin (9NC/Orathecin/Rubitecan) can enhance the effects of radiation. We conducted a phase I study to assess the toxicity and determine the maximum tolerated dose of 9NC when combined with radiation in patients with locally advanced adenocarcinoma of the pancreas.
  
  
  METHODS
  Eleven patients with locally advanced adenocarcinoma of the pancreas received 9NC, orally during radiation. Radiation therapy consisted of 45 Gy in 25 fractions given over 5 weeks. The starting dose of 9NC was 1 mg/m2/day.
  
  
  RESULTS
  Eight patients received 9NC at a dose of 1 mg/m2/day and three patients received a dose of 1.25 mg/m2/day. Dose-limiting toxicity (DLT) was defined as >or=grade 3 non-hematologic toxicity and >or=grade 4 hematologic toxicity. Dose-limiting toxicity of grade 3 nausea/vomiting developed in one patient at the first dose level. At dose level 2, two of three patients developed DLT. Both developed grade 3 nausea, fatigue, and anorexia. Additionally, one of these patients had grade 3 dehydration and the other had grade 4 leukopenia, grade 3 vomiting, and grade 3 weakness.
  
  
  CONCLUSIONS
  9NC, 1 mg/m2/day, can be given concurrently with radiation with acceptable toxicity.
authors.affiliation: Department of Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Tedesco
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: Mace
authors.initials: M
authors.lastname: Rothenberg
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
authors.forename: Ken
authors.initials: K
authors.lastname: Wyman
authors.forename: Adrian
authors.initials: A
authors.lastname: Scott Pearson
authors.forename: Robert
authors.initials: R
authors.lastname: Daniel Beauchamp
authors.forename: Nipun
authors.initials: N
authors.lastname: Merchant
authors.forename: A Craig
authors.initials: AC
authors.lastname: Lockhart
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Carol
authors.initials: C
authors.lastname: Caillouette
authors.forename: Bapsi
authors.initials: B
authors.lastname: Chakravarthy
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy*; D000284:Administration, Oral; D000368:Aged; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage
chemical_list: D011838:Radiation-Sensitizing Agents; C079905:rubitecan; D002166:Camptothecin