Topotecan: Oral chemotherapy agent approved for the treatment of relapsed SCLC

Key Points

Topotecan is a semisynthetic derivative of camptothecin; this antitumor agent acts as a topoisomerase I inhibitor, thus causing double-strand DNA damage during DNA synthesis. This oral formulation of topotecan was approved on October 12, 2007, for the treatment of relapsed small cell lung cancer (SCLC) in patients with a prior complete or partial response who are ≥45 days from the end of first-line chemotherapy.

Efficacy. The efficacy of this agent was evaluated in a randomized, comparative, open-label trial in patients with relapsed SCLC who were prior responders to first-line chemotherapy, were not considered candidates for standard intravenous (IV) chemotherapy, and had relapsed $45 days from the end of first-line chemotherapy. Patients were randomized to oral topotecan 2.3 mg/m² /d for 5 consecutive days, repeated every 21 days, plus best supportive care (BSC) (n=71) or to BSC alone (n=70). The primary end point in the study was overall survival. Patients treated with oral topotecan plus BSC received a median of 4 treatment courses, with a median topotecan dose intensity of 3.77 mg/m²/wk. Patients treated with topotecan plus BSC demonstrated a statistically significant improvement in overall survival (25.9 wk; 95% CI, 18.3–31.6) compared with patients treated with BSC alone (13.9 wk; 95% CI, 11.1–18.6; HR=0.64; 95% CI, 0.45–0.90; log-rank P=.0104).

Safety. Bone marrow suppression (primarily manifested as neutropenia) is a dose-limiting toxicity of topotecan treatment. Topotecan-induced neutro-penia can also lead to neutropenic colitis; fatalities caused by neutropenic colitis have been reported in topotecan-treated patients. Topotecan should be administered only to patients with adequate bone marrow reserves, and patients' peripheral blood cell counts should be closely monitored during treatment. Severe diarrhea has been reported in patients treated with oral topotecan; this treatment-related diarrhea is associated with significant morbidity and should therefore be aggressively managed. This agent may cause fetal harm in pregnant women. The most common adverse events reported in association with topotecan treatment include anemia, leukopenia, neutropenia, thrombocytopenia, nausea, diarrhea, vomiting, alopecia, fatigue, anorexia, asthenia, and pyrexia.