II. Indications
- FDA Approved (often combined with other agents)
- Off-Label
- Acute Myelogenous Leukemia (AML)
- CNS Malignancy (including CNS Lymphoma)
- Ewing Sarcoma
- Neuroblastoma
- Ovarian Cancer (metastatic)
- Rhabdomyosarcoma
III. Mechanism
- See Mitotic Inhibitor Chemotherapy
-
Irinotecan is a semisynthetic derivative of camptothecin with antineoplastic activity
- Camptothecin extracted from the Asian tree Camptotheca acuminata ("Happy Tree")
- Camptothecin is a cytotoxic quinoline-based alkaloid
- Topotecan is active without metabolism
- Contrast with Irinotecan, a similar drug, but that requires metabolism to SN-38 for activity
- Topotecan is considered less potent than SN-38, the active metabolite of Irinotecan
- Topotecan is a Topoisomerase Inhibitor
- Binds to topoisomerase 1, inhibiting DNA ligation
- DNA breaks accumulate
- Inhibits DNA Replication and transcription
- Arrests Cell Cycle in S phase
- Results in cell apoptosis and death
IV. Medications
- Oral Capsules: 0.25 mg and 1 mg
- Powder for IV Injection Solution: 4 mg
V. Dosing
- See other references for disease specific dosing protocols
VI. Adverse Effects
- Myelosuppression (Bone Marrow suppression)
- Bleeding (may be severe)
- Interstitial Lung Disease
VII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters)
- Use reliable Contraception (including one month after Chemotherapy completed)
- Monitoring
VIII. Resources
- Topotecan Injection Solution (DailyMed)
- Topotecan Capsule (DailyMed)
IX. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia