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Long-term follow-up of patients with advanced ovarian cancers treated with intermittent administration of combination chemotherapy with cisplatin, doxorubicin and cyclophosphamide

Despite high primary response rates with cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancers remains dismal. We designed a new systematic treatment approach with a combination chemotherapy consisting of cisplatin, doxorubicin and cyclophosphamide (cyclic PAC chemotherapy), with the aim of improving survival rates with minimal disturbance of quality of life. Cyclic PAC chemotherapy is a three-step chemotherapy with three courses of the PAC regimen in each step. A total of nine courses with a 3-month drug-free period between each step were administered over a 15-month period to patients with clinical stage IC-IV ovarian cancer who had undergone cytoreductive surgery. Forty-eight patients with stage IC-IV disease (34 patients with stage III and IV disease) were treated with cyclic PAC chemotherapy. Thirty-four patients with stage IC-IV disease (23 patients with stage III and IV disease) were treated by a brief course of PAC chemotherapy. Long-term survival and toxicity were evaluated for both treatment groups. Cyclic PAC chemotherapy improved the overall outcome of patients (66.6% 3-year and 56.5% 5-year survival rates) compared to brief PAC (41.2% 3-year and 23.5% 5-year survival rates) (P < 0.01). The outcome of patients with stage III-IV ovarian cancer of the cyclic PAC group (52.6% 3-year and 37.2% 5-year survival rates) was also superior to that of the brief PAC group (21.7% 3-year and 8.7% 5-year survival rates). Generally, the treatment was well tolerated. The toxicity was similar in both groups, although myelosuppresion and neurotoxicity were rather prominent in the cyclic PAC group. Cyclic PAC chemotherapy may lead to improved survival in advanced ovarian cancer, and merits further investigation in a randomized study.