Intralesional topotecan in advanced ovarian cancer: a clinical report, based on a preclinical study

The aim of this study was to evaluate the response of ovarian cancer to intralesionally administered topotecan. Preliminary experiments were carried out in nude mice subcutaneously grafted with three different human ovarian carcinoma cells (A2780, IGROV/DDP and SKOV-3). Topotecan was administered intravenously (i.v.: 10-15 mg/kg every 4th day for 4 times) or intralesionally (i.t.: single dose of 15-20 mg/kg) and tumor size changes/drug toxicity were evaluated. The results indicate that the sensitivity of the three tumor models was different (rank: A2780 > IGROV/DDP > SKOV-3) but, for each tumor line, the pattern of response was similar after i.v. and i.t. administration. No local toxicity was detected, but appreciable systemic toxicity (animal death rate) was observed in spite of the use of a single i.t. dose. The effects of intralesional topotecan administration were then assessed in a patient with an advanced, epithelial ovarian tumor (endometroid type, poorly differentiated histologic grade), already treated with cisplatin and paclitaxel. The treatment (7.5 mg/m(2)) was repeated three times and, although drug plasma levels were in the range generally reported following i.v. administration and typical systemic toxicity occurred, no tumor regression was observed and the patient died 14 months later. We conclude that the intralesional drug delivery is effective to achieve a rapid tumor shrinkage in large tumor lesions, but in the presence of drug resistance, either intrinsic or acquired, intratumor drug administration can not be recommended.