title: Results of a 2-arm Phase II study of 9-nitrocamptothecin in patients with advanced soft-tissue sarcomas.
abstract: BACKGROUND
  The authors conducted a 2-arm Phase II trial of 9-nitrocamptothecin (9-NC), an oral topoisomerase I inhibitor, to define response rates in patients with gastrointestinal (GI) leiomyosarcomas and other soft-tissue sarcomas (STS).
  
  
  METHODS
  Patients were required to provide informed consent and have measurable disease, Zubrod performance status < or = 2, and adequate organ function. 9-NC was administered orally at 1.5 mg/m(2) per day x 5 days every week. Response evaluation was performed at 8 weeks, and those with stable or responding disease continued treatment until maximal response was achieved. A total of 56 patients (30 females and 26 males) with a median age of 55 years (range, 19-79 years) were enrolled on the study. Seventeen patients were enrolled on the GI leiomyosarcoma arm; only 1 minor response, lasting < 8 weeks in a patient with liver metastases, was noted, and so this arm was terminated. Thirty-nine patients were entered on the other STS arm.
  
  
  RESULTS
  Three patients achieved a partial response (response rate, 8%) for durations of 4, 6, and 13 months, respectively. Fourteen patients had stable disease for a median of 4 months (range, 2-8 months). Two patients died of disease during the first 2 months. Four other patients required hospitalization for nausea, vomiting, and dehydration. Other toxicities included diarrhea (36 patients, 5 with Grade 3 toxicity); fatigue (42 patients, 11 with Grade 3 toxicity); anorexia (32 patients, 1 with Grade 3 toxicity); nausea (37 patients, 2 with Grade 3 toxicity); vomiting (24 patients, 3 with Grade 3 toxicity); neutropenia (14 patients, 5 with Grade 3 toxicity); and thrombocytopenia (16 patients, 5 with Grade 3 or 4 toxicity).
  
  
  CONCLUSIONS
  9-NC is well tolerated but inactive in GI leiomyosarcomas and has minimal activity in previously treated patients with STS.
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. spatel@mdanderson.org
authors.forename: Shreyaskumar R
authors.initials: SR
authors.lastname: Patel
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beach
authors.forename: Nicholas
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: M Andrew
authors.initials: MA
authors.lastname: Burgess
authors.forename: Jonathan
authors.initials: J
authors.lastname: Trent
authors.forename: Jan
authors.initials: J
authors.lastname: Jenkins
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C079905:rubitecan; D002166:Camptothecin