Skip to main content

Phase I and pharmacological study of oral 9-aminocamptothecin colloidal dispersion (NSC 603071) in patients with advanced solid tumors.

Publication ,  Journal Article
Xiong, HQ; Tran, HT; Madden, TL; Newman, RA; Abbruzzese, JL
Published in: Clin Cancer Res
June 2003

PURPOSE: 9-Aminocamptothecin colloidal dispersion (9-ACCD; NSC 603071) is a specific inhibitor of topoisomerase I that can be given p.o. This Phase I trial was conducted to determine the toxicity profile, maximal tolerated dose, and pharmacokinetics profile, including bioavailability, of p.o. 9-ACCD in patients with advanced solid tumors. EXPERIMENTAL DESIGN: After receiving one i.v. dose of 9-ACCD, patients were treated with 9-ACCD p.o., starting with a 2-week schedule, to establish the safety. Once safety was established, patients were treated continuously for 4 weeks followed by a rest period of 2 weeks at dosages of 0.2, 0.3, 0.45, 0.56, 0.7, and 0.63 mg/m(2)/day. Serial blood samples were collected for the pharmacokinetics study on day 1 after the i.v. dose and day 2 after p.o. administration. Lactone and total 9-aminocamptothecin were analyzed by high-pressure liquid chromatographic assay. RESULTS: Thirty-two patients were treated on the study. The dose-limiting toxicity was myelosuppression at the dosage of 0.7 mg/m(2)/day. Other toxic effects included nausea, vomiting, fatigue, and transient elevation of the total bilirubin level. The maximal tolerated dose was 0.63 mg/m(2)/day. There was no objective response. The mean terminal half-life of p.o. total 9-ACCD was 1.2 +/- 1.2 h, and the volume of distribution was 17.7 +/- 20.6 l/m(2). The mean bioavailability of total 9-ACCD was 68.1 +/- 36.4%. CONCLUSIONS: Despite good tolerance of p.o. administration, the lack of clinical activity and variable absorption of 9-ACCD suggested that further development might not be warranted.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

June 2003

Volume

9

Issue

6

Start / End Page

2066 / 2071

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Female
  • Camptothecin
  • Antineoplastic Agents
  • Aged
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xiong, H. Q., Tran, H. T., Madden, T. L., Newman, R. A., & Abbruzzese, J. L. (2003). Phase I and pharmacological study of oral 9-aminocamptothecin colloidal dispersion (NSC 603071) in patients with advanced solid tumors. Clin Cancer Res, 9(6), 2066–2071.
Xiong, Henry Q., Hai T. Tran, Timothy L. Madden, Robert A. Newman, and James L. Abbruzzese. “Phase I and pharmacological study of oral 9-aminocamptothecin colloidal dispersion (NSC 603071) in patients with advanced solid tumors.Clin Cancer Res 9, no. 6 (June 2003): 2066–71.
Xiong HQ, Tran HT, Madden TL, Newman RA, Abbruzzese JL. Phase I and pharmacological study of oral 9-aminocamptothecin colloidal dispersion (NSC 603071) in patients with advanced solid tumors. Clin Cancer Res. 2003 Jun;9(6):2066–71.
Xiong HQ, Tran HT, Madden TL, Newman RA, Abbruzzese JL. Phase I and pharmacological study of oral 9-aminocamptothecin colloidal dispersion (NSC 603071) in patients with advanced solid tumors. Clin Cancer Res. 2003 Jun;9(6):2066–2071.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

June 2003

Volume

9

Issue

6

Start / End Page

2066 / 2071

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Female
  • Camptothecin
  • Antineoplastic Agents
  • Aged