A phase II pharmacodynamic study of pyrazoloacridine in patients with metastatic colorectal cancer.

Abstract

PURPOSE:

To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy.

METHODS:

PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed.

RESULTS:

No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1-6). Toxicity included neutropenia and neurologic side-effects, which were > or = grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P = 0.04).

CONCLUSIONS:

PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity.

• Authors: R Pelley, R Ganapathi, L Wood, L Rybicki, D McLain, G T Budd, D Peereboom, T Olencki, R M Bukowski
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 46 Issue 3 Pg. 251-4 ( 2000) ISSN: 0344-5704 [Print] Germany
• PMID: 11021744 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Acridines
• Antineoplastic Agents
• Intercalating Agents
• Pyrazoles
• NSC 366140

Topics

• Acridines (adverse effects, pharmacokinetics, therapeutic use)
• Adult
• Aged
• Antineoplastic Agents (adverse effects, pharmacokinetics, therapeutic use)
• Colonic Neoplasms (blood, drug therapy)
• Female
• Humans
• Intercalating Agents (adverse effects, pharmacokinetics, therapeutic use)
• Male
• Middle Aged
• Neoplasm Metastasis
• Nervous System Diseases (chemically induced)
• Neutropenia (chemically induced)
• Pyrazoles (adverse effects, pharmacokinetics, therapeutic use)
• Rectal Neoplasms (blood, drug therapy)