Gridelli C
Divisione di Oncologia Medica B, Istituto Nazionale Tumori, Napoli.
Tumori. 1999 Nov-Dec;85(6 Suppl 1):S16-22.
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.
拓扑替康是治疗肺癌的一种新型活性药物。在晚期非小细胞肺癌（NSCLC）中，其客观缓解率（OR）为0 - 15%，在MD安德森癌症中心对40例患者进行的最大规模II期研究中为15%。在与新药联合化疗中，尤其是与吉西他滨联合，已报道了有趣的结果。然而，拓扑替康在NSCLC中的作用仍需进一步试验来明确。拓扑替康是小细胞肺癌（SCLC）中活性最高的药物之一。特别是，它在经预处理的敏感患者中显示出活性，OR为14% - 38%。在对预处理患者进行的III期随机试验中，单药拓扑替康显示出相似的OR和生存率，但与CAV方案（环磷酰胺 + 阿霉素 + 长春新碱）相比，姑息效果更好。在一线化疗中，拓扑替康单药治疗的OR为39%。在联合化疗中，尤其是与紫杉醇联合，已显示出有趣的结果。多项研究正在进行中。拓扑替康作为一线化疗可用于旧的双联组合（如顺铂或卡铂 + 拓扑替康）、新的双联组合（如紫杉醇或长春瑞滨或吉西他滨 + 拓扑替康）、三联化疗组合（如顺铂或卡铂 + 紫杉醇 + 拓扑替康）以及序贯或交替化疗方案。拓扑替康在脑中达到高药物浓度。它在SCLC脑转移中显示出活性，经预处理患者的OR为40% - 63%，完全缓解率为13% - 43%。这种特殊活性在一线化疗中可考虑用于预防脑转移或治疗诊断时伴有脑转移的患者。口服拓扑替康是一种非常有吸引力的药物。它在未经治疗的SCLC患者中的OR为36%，在经预处理患者中的OR为23%。与静脉用药相比，口服制剂似乎毒性较小。未来，拓扑替康应开发为一线联合放化疗，以充分发挥其放射增敏作用。其对脑转移的活性也必须进一步研究。口服制剂很有吸引力，因为它毒性较小，可用于毒性较小的方案，特别是在初治或老年患者中。然而，在未来几年，拓扑替康的作用将通过进行III期随机试验得到更好的明确。
