Topotecan

Topotecan (CAS No. 123948-87-8) is a semi-synthetic camptothecin derivative. Its core target is topoisomerase I (Topo I). By forming a stable, cleavable DNA/Topo I/drug complex, it blocks DNA replication and repair and induces cell apoptosis. Its activity is characterized by cytostatic effects and clinical efficacy.

The concentration commonly used in experiments is 0.1–10 μM (for in vitro tumor cell assays). In combination therapy experiments, the dosage can be adjusted to 0.75–1.5 mg/m² (in vitro equivalent concentration based on clinical conversion). The clinically effective therapeutic concentration corresponds to multiple administration regimens: the conventional intravenous dose is 1.5 mg/m² per day (administered consecutively for 5 days, with a 21-day cycle). For the treatment of recurrent ovarian cancer, it can be combined with drugs such as cisplatin (CAS No. 15663-27-1, Catalog No.: A8321). For first-line treatment of small cell lung cancer (SCLC), it can be used in combination with paclitaxel (CAS No. 33069-62-4, Catalog No.: A4393), etoposide (CAS No. 33419-42-0, Catalog No.: A1971), and other agents. The oral formulation has a bioavailability of 30%–40%, with a commonly used dose of 2.3 mg/m² per day (administered consecutively for 5 days).

Its biological activity is reflected in broad-spectrum antitumor effects, with definite efficacy against ovarian cancer, SCLC, and other malignancies. It can cross the blood-brain barrier and has no cross-resistance with cisplatin, paclitaxel, and similar drugs. Its main toxicity is reversible neutropenia, with mild non-hematological toxicities. It is indicated for the treatment of recurrent ovarian cancer, SCLC, and certain solid tumors.

References:

[1] Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C. Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. doi: 10.1159/000011923. PMID: 9885371.

[2] Ardizzoni A. Topotecan in the treatment of recurrent small cell lung cancer: an update. Oncologist. 2004;9 Suppl 6:4-13. doi: 10.1634/theoncologist.9-90006-4. PMID: 15616145.

[3] Stewart DJ. Topotecan in the first-line treatment of small cell lung cancer. Oncologist. 2004;9 Suppl 6:33-42. doi: 10.1634/theoncologist.9-90006-33. PMID: 15616148.

[4] Lihua P, Chen XY, Wu TX. Topotecan for ovarian cancer. Cochrane Database Syst Rev. 2008 Apr 16;2008(2):CD005589. doi: 10.1002/14651858.CD005589.pub2. PMID: 18425923; PMCID: PMC6905487.