Topoisomerase-I activity and response to second-line chemotherapy consisting of camptothecin-11 and cisplatin in patients with ovarian cancer

The aim of the present study was to clarify the relationship between topois omerase-1 (topo-1) activity and sensitivity to second-line chemotherapy con sisting of cisplatin and camptothecin-11 (CPT-11) in patients with ovarian cancer. Thirty Japanese women with relapsed epithelial ovarian cancer who r eceived treatment at Tottori University Hospital or Kurume University Hospi tal between 1992 and 1997 were included in this study. All patients had ini tially undergone chemotherapy consisting of cisplatin, doxorubicin and cycl ophosphamide (CAP). All subjects exhibited measurable lesions and received second-line chemotherapy consisting of 50 to 60 mg/m(2) CPT-11 on days 1, 8 and 15 and 60 mg/m(2) cisplatin on day 1. Tumor samples were obtained in t he period between initial and second-line chemotherapy. Topo-1 activity was assayed by relaxation of supercoiled plasmid substrate DNA. Of the 30 pati ents, 18 responded to second-line chemotherapy and 12 did not. We found no significant difference in patient characteristics in responders and non-res ponders. The interval from the end of the initial course of chemotherapy to the beginning of the second-line chemotherapy did not significantly differ in the 2 groups. The minimum amount of extraction showing complete DNA rel axation in non-responders was significantly greater than that in responders (201.7 +/- 92.5 vs. 124.1 +/- 59.4 ng; p = 0.0164). In 8 cases whose sampl es could be obtained before and after CAP, the amount of protein significan tly decreased after CAP therapy (286.4 +/- 142.1 vs. 138.5 +/- 97.8 ng; P = 0.0294). Topo-1 activity, which is enhanced by CAP therapy, can play an im portant role in sensitivity to CPT-11. Int. J. Cancer (Pred. Oncol.) 84:521 -524, 1999. (C) 1999 Wiley-Liss, Inc.