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Pronunciation:

(a min o camp to THE sin)

Synonyms:

9-AC; 9-Aminocamptothecin; NSC-603071

Generic Available:

Use - Unlabeled/Investigational:

Phase II trials: Relapsed lymphoma, refractory breast cancer, nonsmall cell lung cancer, untreated colorectal carcinoma

Contraindications:

Hypersensitivity to aminocamptothecin or any component of the formulation

Adverse Reactions:

Frequency not defined.

Central nervous system: Fatigue

Dermatologic: Alopecia

Gastrointestinal: Nausea, vomiting, diarrhea, mucositis, anorexia

Hematologic: Neutropenia (may be dose-limiting), thrombocytopenia (reversible, but may be dose-limiting depending on administration schedule), anemia

Drug Interactions:

Patients taking anticonvulsants that induce hepatic enzymes have less toxicity and can tolerate higher doses of aminocamptothecin.

Stability:

Store ampuls at room temperature. Contents of ampul are added to vial (supplied) containing 24.5 mL of special diluent. Resulting aminocamptothecin concentration is 100 mcg/mL. Further dilution with special diluent for administration via syringe pump is acceptable. May further dilute with NS if resulting concentration is <1 mcg/mL. Diluted solutions are stable for 28 hours at room temperature. Undiluted aminocamptothecin should not contact plastic items.

Mechanism of Action:

Aminocamptothecin binds to topoisomerase I, stabilizing the cleavable DNA-topoisomerase I complex, resulting in arrest of the replication fork and inhibition of DNA synthesis.

Pharmacodynamics/Kinetics:

Ratio of lactone to total drug is 8.7 ± 4.7% because of instability of aminocamptothecin lactone in plasma.

Distribution: Vd: 46-92 L

Metabolism: None identified

Half-life elimination: Terminal: 8-17 hours for total aminocamptothecin

Excretion: Urine (32% of total drug delivered)

Dosage:

I.V.: Adults: 45-59 mcg/m²/hour for 72 hours as a continuous infusion; repeat every 2 weeks or 35 mcg/m²/hour as a 72-hour continuous infusion

Administration:

Administer by continuous I.V. infusion.

Monitoring Parameters:

WBC with differential, platelet count

Dental Health: Effects on Dental Treatment:

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Mental Health: Effects on Mental Status:

May cause sedation

Mental Health: Effects on Psychiatric Treatment:

May cause GI side effects; concomitant use with SSRIs, lithium, or vaproic acid may produce additive effects; monitor. May cause neutropenia and thrombocytopenia; monitor if using concomitantly with clozapine, valproic acid, and carbamazepine.

Oncology: Emetic Potential:

Moderate (30% to 60%)

Oncology: Vesicant:

Dosage Forms:

Injection: 5 mg ampul

References

Grossman SA, Hochberg F, Fisher J, et al, "Increased 9-Aminocamptothecin Dose Requirements in Patients on Oral Anticonvulsants. NAPTT CNS Consortium. The New Approaches to Brain Tumor Therapy,"Cancer Chemother Pharmacol, 1998, 42(2):118-26.

Iyer L and Ratain MJ, "Clinical Pharmacology of Camptothecins,"Cancer Chemother Pharmacol, 1998, 42(Suppl):31-43.

Potmesil M, Arbuck SG, Takimoto CH, et al, "9-Aminocamptothecin and Beyond. Preclinical and Clinical Studies,"Ann N Y Acad Sci, 1996, 803:231-46.

Takimota CH, Wright J, and Arbuck SG, "Clinical Applications of the Camptothecins,"Biochim Biophys Acta, 1998, 1400(1-3):107-19.

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