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.
Publication types
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Clinical Trial
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Clinical Trial, Phase II
MeSH terms
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Acridines / adverse effects
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Acridines / pharmacokinetics
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Acridines / therapeutic use*
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Adult
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Aged
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use*
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Colonic Neoplasms / blood
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Colonic Neoplasms / drug therapy*
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Female
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Humans
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Intercalating Agents / adverse effects
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Intercalating Agents / pharmacokinetics
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Intercalating Agents / therapeutic use*
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Male
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Middle Aged
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Neoplasm Metastasis
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Nervous System Diseases / chemically induced
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Neutropenia / chemically induced
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Pyrazoles / adverse effects
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Pyrazoles / pharmacokinetics
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Pyrazoles / therapeutic use*
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Rectal Neoplasms / blood
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Rectal Neoplasms / drug therapy*
Substances
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Acridines
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Antineoplastic Agents
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Intercalating Agents
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Pyrazoles
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NSC 366140