Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death).

Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (-1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor.

Ovarian Cancer: Topotecan for injection, as a single agent, is indicated for the treatment of patients with metastatic carcinoma of the ovary after disease progression on or after initial or subsequent chemotherapy.

Small Cell Lung Cancer: Topotecan for injection, as a single agent, is indicated for the treatment of patients with small cell lung cancer with platinum-sensitive disease who progressed at least 60 days after initiation of first-line chemotherapy.

Cervical Cancer: Topotecan for injection in combination with cisplatin is indicated for the treatment of patients with Stage IV-B, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment.

Verify dose using body surface area prior to dispensing. Recommended dosage should generally not exceed 4 mg intravenously 

Ovarian Cancer: The recommended dose of Topotecan is 1.5 mg/m² by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course.

Small Cell Lung Cancer: The recommended dose of Topotecan is 1.5 mg/m² by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course.

Cervical Cancer: The recommended dose of Topotecan is 0.75 mg/m² by intravenous infusion over 30 minutes daily on Days 1, 2, and 3 in combination with cisplatin 50 mg/m² on Day 1, repeated every 21 days.

Severe bone marrow depression (e.g. baseline neutrophil count of <1500 cells/mm³ and platelet count <100,000/mm³). Pregnancy, lactation, severe renal or hepatic impairment.

Neutropenia (nadir of white cell count occurs about 9-12 days after admin), thrombocytopenia and anaemia. GI upset, total alopecia, headache, dyspnoea. Fatigue, weakness, malaise, pruritus and hyperbilirubinaemia.

Overdose Effects

Symptoms: Bone marrow supression

Preexisting bone marrow depression. Frequent monitoring of peripheral blood cell counts during treatment. Do not continue subsequent courses until neutrophils recover to >1000 cells/mm³, platelets recover to >100,000 cells/mm³ and haemoglobin levels recover to 9.0 g/dl (with transfusion if needed). May impair ability to drive or operate machinery.

Use in Special Populations

Renal Impairment:

• Ovarian carcinoma, Small cell lung cancer: CrCl 20-30: Initial dose 0.75 mg/m².
• Cervical cancer: Treatment to be initiated only if serum creatinine ≤1.5 mg/dl.

Hepatic Impairment: Avoid

Pregnancy & Lactation

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).