Results of a 2-arm Phase II study of 9-nitrocamptothecin in patients with advanced soft-tissue sarcomas

Cancer. 2003 Jun 1;97(11):2848-52. doi: 10.1002/cncr.11385.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents / toxicity
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use*
  • Camptothecin / toxicity
  • Female
  • Gastrointestinal Neoplasms / drug therapy
  • Humans
  • Leiomyosarcoma / drug therapy
  • Male
  • Middle Aged
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality
  • Topoisomerase I Inhibitors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Topoisomerase I Inhibitors
  • rubitecan
  • Camptothecin