[Topotecan, a recent discovery and prospects for treating tumors of the lung]

Topotecan is a new active drug in the treatment of lung cancer. In advanced non small cell lung cancer (NSCLC) it showed 0-15% of objective response (OR) with 15% in the largest phase II study performed on 40 patients at the M.D. Anderson Cancer Center. Interesting results have been reported in combination chemotherapy with new drugs, in particular with gemcitabine. However, the role of topotecan in NSCLC must be developed in further trials. Topotecan is one of the most active drug in small cell lung cancer (SCLC). Particularly, it showed active in sensitive pretreated patients with 14%-38% OR. In a phase III randomized trial performed in pretreated patients, single agent topotecan showed similar OR and survival but better palliative effect compared to the CAV regimen (cyclophosphamide + adryamicin + vincristine). In first line chemotherapy topotecan showed 39% OR as single agent. Interesting results have been showed in combination chemotherapy in particular with taxol. Several studies are ongoing. Topotecan as first line chemotherapy could be developed in old doublet combinations (such as cisplatin or carboplatin + topotecan), new doublet combinations (such as taxol or vinorelbine or gemcitabine + topotecan), triplet chemotherapy combinations (such as cisplatin or carboplatin + taxol + topotecan) and sequential or alternate chemotherapy regimens. Topotecan reaches high drug concentration in the brain. It showed activity in brain metastases of SCLC with 40%-63% OR and 13%-43% of complete response in pretreated patients. This particular activity could be considered in first line chemotherapy as prophylaxis of brain metastases or to treat patients with brain metastases at diagnosis. Oral topotecan is a very interesting drug. It showed 36% OR in outfit untreated SCLC patients and 23% in pretreated patients, respectively. Oral formulation seems to induce less toxicity when compared to the intravenous drug. In the future topotecan should be developed as first line combined radio-chemotherapy treatment to make the best of its radiosensitizer effect. The activity on brain metastases also must be developed. Oral formulation is interesting because it is less toxic and could be considered in less toxic regimens in particular in outfit or elderly patients. However in the next years the role of topotecan will be better defined performing phase III randomized trials.