| Research Abstract |
Among advanced ovarian malignancies, clear cell adenocarcinoma of the ovary (OCCA) has worse prognosis compared with the more commom serous cystadenocarcinoma, mainly because of poor sensitivity of OCCA to CDDP-based chemotherapy^1. Indeed, there has been no one patient with pure OCCA showing an appreciable response to chemotherapy. OCCA has recently been increasing in prevalence and has occupied approximately more than 20% of all ovarian cancer. Thus, there is an urgent need to find an effective chemotherapeutic regimen for OCCA.We conducted in vitro chemosensitivity test assessing anti-tumor activities of various agents against OCCA using two cell lines, HAC-2 and KK,established from patients with OCCA.The results showed that 50% growth inhibition was obtained by 0.5ng/ml of SN-38 (active form of CPT-11), 8.1ng/ml of MMC,10.7ng/ml of DOX,110.0ng/ml of etoposide, and 130ng/ml of CDDP.In vivo tumor growth inhibitory test using HAC-2 cells transplanted into BALB/C nude mice demonstrated
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that MMC was the most potent agent, followed by DOX,CPT-11, etoposide, and CDDP.Moreover, a combination of CPT-11 and MMC at the same dose intensity as that of a single agent exhibited by far the highest anti-tumor activity in this model. The same results were obtained in other OCCA cell lines.
Based on the above results, we designed a combination of CPT-11 and MMC.Protocol was as follows ; CPT-11,140mg/m^2 in 500ml of saline infused over 4 hours on day 1,14, and 28 ; and MMC,7mg/m^2 bolus on day 1,14, and 28. The course was repeated every 4 weeks. At least 2 courses of this regimen were given to patients. Among total 60 courses for consecutive 25 patients with pure OCCA,grade 3 diarrhea was observed in 6 courses. Other toxic signs were acceptable. The responses were 5 complete responses (CRs), 8 partial responses (PRs), 9 no changes (NCs), and 3progressive diseases (PDs), with overall response rate being 52% (95% Confidence interval : 32.4% -71.6%). Thirteen responders showed a significantly longer survival compared with 12 non-responders (median survival after the start of chemotheraphy : 22 months vs 7months, p < 0.001 for Log-rank test).HAThus, the present protocol is the first to demonstrate a significant activity in patients with pure OCCA. Less
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