Vinorelbine and the topoisomerase 1 inhibitors: Current and potential roles in breast cancer chemotherapy

Vinorelbine is a semi-synthetic vinca alkaloid which was initially developed in France in the 1980's. Due to its unique structure it is considerably less neurotoxic than vincristine. Several phase II studies have shown that vinorelbine is active in metastatic breast cancer therapy with response rates of 20-30% in pretreated and 40-50% in nonpretreated patients respectively. Higher response rates have been noted when vinorelbine is used in combination regimens. The main dose-limiting toxicity seen with this agent has been neutropenia; neurotoxicity manifest as symptomatic paresthesia can be seen in 10% of treated patients. Oral and implantable forms of the drug have also been investigated. The topoisomerase 1 inhibitors topotecan and camptothecin 11 (CPT-11) have been less extensively evaluated in breast cancer therapy. Preclinical studies have indicated that both of these agents are active against breast cancer and some responses have been seen in phase 1 trials of topotecan. An 8% response rate was noted in a phase II trial of CPT-11 in patients with pretreated metastatic breast cancer. Further phase II trials are ongoing at present with both agents.