Phase II study of 9-nitro-camptothecin in patients with advanced chordoma or soft tissue sarcoma

J Clin Oncol. 2005 May 20;23(15):3597-604. doi: 10.1200/JCO.2005.02.170.

Abstract

Purpose: The purpose of this trial was to assess the objective clinical response, toxicity, and time to progression of treatment with 9-Nitro-Camptothecin (9-NC) in patients with advanced chordoma, soft tissue sarcoma (STS), and gastrointestinal stromal tumor (GIST).

Patients and methods: Patients with locally advanced and/or metastatic chordoma, STS, or GIST received 9-NC 1.25 mg/m2 orally for 5 consecutive days followed by 2 days of rest. Patients continued on therapy until disease progression, uncontrollable toxicity, or withdrawal of consent.

Results: From January 2000 to May 2003, 51 patients (15 chordoma, 23 STS, 13 GIST patients) enrolled. One patient (7%) with chordoma and one patient (4%) with STS had an objective response. Median time to progression was 9.9, 8.0, and 8.3 weeks for chordoma, STS, and GIST patients, respectively. Three- and 6-month progression-free survival rates were 47% and 33% for chordoma patients, 26% and 22% for STS patients, and 31% and 23% for GIST patients, respectively. Ten patients (10%) stopped study drug before disease progression secondary to toxicity. Common adverse events included anemia (42 patients, seven with grade 3/4 toxicity), leukopenia (33 patients, nine with grade 3/4 toxicity), fatigue (30 patients, three with grade 3/4 toxicity), nausea (34 patients, six with grade 3/4 toxicity), and diarrhea (28 patients, five with grade 3/4 toxicity).

Conclusion: 9-NC has modest activity in delaying progression in patients with unresectable or metastatic chordoma. 9-NC is associated with moderate toxicity and shows little benefit in patients with advanced STS and GIST.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Camptothecin / adverse effects
  • Camptothecin / therapeutic use*
  • Chordoma / drug therapy*
  • Chordoma / mortality
  • Chordoma / pathology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Staging
  • Probability
  • Risk Assessment
  • Sarcoma / drug therapy*
  • Sarcoma / mortality
  • Sarcoma / pathology
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / mortality
  • Soft Tissue Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Phytogenic
  • Camptothecin