A North Central Cancer Treatment Group Phase II trial of 9-aminocamptothecin in previously untreated patients with measurable metastatic colorectal carcinoma.

Abstract

BACKGROUND:

Topoisomerase I inhibitors have demonstrated clinical activity in patients with metastatic colorectal carcinoma. The authors performed a Phase II study to evaluate the objective tumor response rate of 2 different doses and schedules of 9-aminocamptothecin (9-AC) in previously untreated patients with measurable recurrent metastatic colorectal carcinoma.

METHODS:

Fifty-one patients were registered. One schedule evaluated 9-AC given at 1100 microgram/m(2)/24 hours by continuous infusion for 72 hours along with granulocyte-colony stimulating factor at 5 microgram/kg/day on Days 5 through 12. Another schedule involved 9-AC at 480 microgram/m(2)/24 hours by continuous infusion for 120 hours on Days 1, 8, and 15 given every 4 weeks.

RESULTS:

Forty-eight of 51 patients (94%) were evaluable (28 patients who received 72-hour infusion and 20 patients who received 120-hour infusion) for response and toxicity. Significant hematologic toxicities were encountered, especially with the 72-hour infusion schedule, in which 43% (12 of 28) and 28% (8 of 28) experienced Grade 4 (National Cancer Institute Common Toxicity Criteria) leukopenia and thrombocytopenia, respectively. Grade 4 neutropenia was encountered in 61% (17 of 28) and 11% (2 of 19) of patients on the 72-hour and 120-hour infusion schedules, respectively. Diarrhea, nausea, vomiting, and hepatotoxicity were troublesome nonhematologic toxicities. Seventy-nine percent (11 of 14) and 57% (4 of 7) of the patients experiencing Grade 3 or 4 nonhematologic toxicity were on the 72-hour infusion schedule. Three patients died of chemotherapy-related toxicity. One response was observed in 48 evaluable patients (2%).

CONCLUSIONS:

9-AC did not demonstrate sufficient antitumor activity and had unacceptable toxicity in previously untreated patients with metastatic colorectal carcinoma.

• Authors: H C Pitot, J A Knost, M R Mahoney, J Kugler, J E Krook, A K Hatfield, D J Sargent, R M Goldberg
• Journal: Cancer (Cancer) Vol. 89 Issue 8 Pg. 1699-705 (Oct 15 2000) ISSN: 0008-543X [Print] United States
• PMID: 11042563 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2000 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Granulocyte Colony-Stimulating Factor
• 9-aminocamptothecin
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Colorectal Neoplasms (drug therapy, pathology)
• Disease Progression
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Survival Analysis
• Time Factors