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Background: The aim of this phase II study was to evaluate the efficacy and toxicity of docetaxel and irinotecan combination chemotherapy in patients with ovarian cancer refractory and resistant to both platinum and taxan treatment., Patients and Methods: Patients who had been treated with platinum and paclitaxel but whose ovarian cancer progressed or recurred within 6 months of treatment (n = 41) received docetaxel 60 mg/m(2) (day 1) and irinotecan 60 mg/m(2) (days 1, 8), repeated every 21 days [Japan Gynecologic Oncology Group (JGOG) study 3015] or every 28 days [West Japan Gynecologic Oncology Group (WJGOG) study 002] until disease progression was observed or unacceptable toxicity. Sixteen patients had platinum/paclitaxel-refractory disease, and 25 patients had platinum/paclitaxel-resistant disease., Results: Thirty-two patients were available for determination of the clinical response. The overall response rate [complete response (CR) + partial response (PR)] was 6.3%, and the disease control rate (CR + PR + stable disease) was 34.4%. Among the 23 patients with resistant tumor, the disease control rate was 47.8%. Ten patients with refractory tumor showed a 10% disease control rate. The median progression-free interval was 12.1 weeks and the median overall survival time was 45.3 weeks. The major toxic adverse effect was neutropenia (grade 4, 56.1%), but the incidence of neutropenic fever was less frequent (4.9%). Neurotoxicity and gastro-intestinal toxicity were mild., Conclusion: Among our patients, a combination of docetaxel and irinotecan was well tolerated. However, this combination may not be a beneficial option for patients with platinum-refractory and -resistant ovarian cancer in terms of response rate and survival.

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, has been preliminarily recognized as an effective agent against clear cell carcinoma of the ovary (CCC), but there are few clinical data. Our aim was to compare progression-free survival (PFS) between patients treated with irinotecan hydrochloride and cisplatin (CPT-P) and those with treated with paclitaxel and carboplatin (TC)., Methods: One hundred and seventeen patients at International Federation of Gynecology and Obstetrics (FIGO) stages Ic (ascites/malignant washing) - IV were identified by scanning the medical records of ten Japanese hospitals. After complete surgical staging procedures including lymphadenectomy, 35 patients received CPT-P and 82 patients received TC. The PFS and overall survival of the two groups were compared using the Kaplan-Meier method., Results: There was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, or follow-up period between the CPT-P and TC groups. Two-year and 5-year PFS was 48% and 40%, respectively, in the TC group and 55% and 55%, respectively, in the CPT-P group (P = 0.31). Multiple regression analysis revealed that only residual tumor was an independent prognostic factor for PFS (P < 0.01)., Conclusion: CPT-P showed a potential therapeutic effect, at least no less than that of TC therapy. Although there was no significant survival benefit in the present retrospective analysis, we recommend that the CPT-P regimen be evaluated in a larger, prospective, clinical trial.

The conventional local treatment methods (surgery and radiation) for cervical cancer have reached a plateau in terms of survival benefit and, therefore, in this review, new treatment strategies (combined chemotherapy [CT] and local therapy) to overcome the poor prognosis were examined in high-risk groups. The effectiveness of neoadjuvant chemotherapy (NAC) administered prior to radiotherapy (RT) has not been confirmed for any disease stages. But NAC followed by surgery may improve survival in patients with stage Ib2 compared with surgery alone; and in patients with stage Ib2 to IIB compared with RT alone. Five large randomized clinical trials (RCTs) demonstrated a significant survival benefit for patients treated with concurrent chemoradiotherapy (CCRT), using a cisplatin (CDDP)-based regimen, with a 28%-50% relative reduction in the risk of death. In addition, the results of a metaanalysis of 19 RCTs of CCRT (1981-2000) involving 4580 patients showed that CCRT significantly improved overall survival (OS) hazard ratio ([HR] 0.71; P < 0.0001), as well as progression-free survival (PFS; HR 0.61; P < 0.0001). In line with these results, CCRT is currently recommended as standard therapy for advanced cancer (stage III/IVA) in the United States. However, there remains much controversy and uncertainty regarding the optimal therapeutic approaches, especially for patients with advanced cancer. Additional RCTs should be conducted to find the optimal CT regimen and RT for Japanese patients, considering acute and late complications, as well as differences in pelvic anatomy, total radiation dose, and RT procedures between Japan and other countries. Evidence obtained from such studies should establish the optimal CCRT treatment protocol and define the patient population (disease stage) that the protocol really benefits.

Background: We investigated the clinical usefulness and toxicity of salvage treatment with docetaxel (70 mg/m2) infused at 3-week intervals in patients with recurrent ovarian cancer., Methods: Retrospectively, we reviewed the clinical records of 24 patients diagnosed with recurrent ovarian cancer who had received the salvage treatment., Results: A total of 128 courses (median, 5.5 courses; range, 2-8 courses) were administered to the 24 patients. The mean number of prior chemotherapy courses in the patients was 16.4 (range, 4-35 courses); they had already been treated heavily. The tumor response was evaluable at the end of the treatment in 20 patients, with the overall response rate being 15.0%. Using the criterion of serum carbohydrate antigen (CA)125 level, the response rate was 13.0%. By the time of the final docetaxel treatment, all 24 patients had relapsed and 19 had died of the disease. The median progression-free interval was 4.6 months (range, 1.3-7.8 months), and the median overall survival time was 13.7 months (range, 2.1-27.0 months). While hematological toxicity was not severe, 20.8% of patients experienced grade 3 asthenia/fatigue, and 5 patients refused further treatments with docetaxel because of this toxicity., Conclusions: Salvage treatment using docetaxel (70 mg/m2) was somewhat effective for recurrent ovarian cancer, although severe asthenia/fatigue was frequently observed. Docetaxel provides sufficient palliation of disease-related symptoms and some improvement in the length of life in patients with recurrent ovarian cancer, when asthenia/fatigue is mild.

Background: A multicenter, phase I study of combination therapy with paclitaxel and carboplatin for epithelial ovarian cancer was conducted to determine the safety and recommended dosages for Japanese women., Methods: Paclitaxel was administered intravenously over a 3-h period, followed by carboplatin administered intravenously over a 1.5-h period. A modified continual reassessment method (mCRM) was used in two treatment arms to establish the maximum tolerated dose (MTD) and recommended doses of the combination. In group A, the dose of paclitaxel (175 mg/m2) was constant and the dose of carboplatin was increased from 4 to 7 in terms of the target area under the plasma concentration-versus-time curve (AUC). In group B, the dose of carboplatin was constant (AUC 6) and paclitaxel was administered at two dose levels (160 and 175 mg/m2). In both groups, the carboplatin dose was limited to a maximum of 800 mg/body for each administration., Results: Because the calculated probability of toxicity was greatest at a dose of paclitaxel 175 mg/m2 and carboplatin AUC 7, this dose was designated the MTD in group A. Based on this result, treatment in group B was initiated at doses of paclitaxel of 160 mg/m2 and carboplatin AUC 6. While the dose of paclitaxel was escalated to 175 mg/m2, the safety of the combination was confirmed. The most frequent adverse effect was neutropenia, which resolved promptly with the appropriate use of granulocyte-colony stimulating factor (G-CSF). No other severe hematologic or nonhematologic toxicities were observed., Conclusions: Our study demonstrated that the recommended dose for this combination regimen should be paclitaxel 175 mg/m2 plus carboplatin AUC 6 (maximum dose, 800 mg/body).

Background: The clinical response, survival, and toxicity of a 3-h infusion of single-agent paclitaxel (175 mg/m2) for Japanese patients with recurrent ovarian cancer were investigated. We also examined whether or not cancer antigen (CA) 125 would be suitable as an indicator of the effects of the paclitaxel on ovarian cancer., Methods: Twenty-one patients clinically diagnosed as having recurrent ovarian cancer met the entry criteria, agreed to participate in this study, and received the treatment., Results: One hundred and twenty-six courses were administered to the 21 patients. One patient achieved a complete response, and 5 a partial response; the overall response rate was 35.3%. Using CA125 criteria, 42.1% of patients achieved a response. The median progression-free interval was 4.4 months, and the median overall survival time was 14.5 months. While hematological toxicity was not severe, 3 patients experienced severe peripheral neuropathy, and 2 patients experienced grade 4 myalgia/arthralgia., Conclusion: The 3-h infusion of single-agent paclitaxel (175 mg/m2) was an effective treatment for patients with recurrent ovarian cancer. CA125 was a useful indicator of the response to the treatment. While peripheral neuropathy and the myalgia/arthralgia were severe, 3-h infusion of single-agent paclitaxel offers a promising treatment for recurrent ovarian cancer.