Ovarian sex cord-stromal tumors in children and adolescents.

PURPOSE: To develop diagnostic standards and a risk-adapted therapeutic strategy for ovarian sex cord-stromal tumors (OSCST). PATIENTS AND METHODS: Fifty-four patients were prospectively enrolled as follow-up patients onto the German Maligne Keimzelltumoren protocols. Surgical protocols and histopathology were reviewed centrally (53 patients with complete data). Surgery included ovariectomy in 18 patients, salpingo-ovariectomy in 34 patients, and hysterectomy in one patient. Patients with stage IA tumors were followed-up at regular intervals, whereas nine patients with stage IC and six patients with stage II to III tumors were treated with cisplatin-based chemotherapy. RESULTS: International Federation of Gynecology and Obstetrics stage was IA in 27 patients, IC in 21 patients, II in three patients, and III in three patients. After a median follow-up of 59 months (range, 6 to 193 months), event-free survival +/- SD was 0.86 +/- 0.05 (47 of 54 patients) and overall survival was 0.89 +/- 0.05 (49 of 54 patients). Prognosis correlated with stage (event-free survival +/- SD: IA, 1.0 [27 of 27 patients]; IC, 0.76 +/- 0.09 [16 of 21 patients]; and II/III, 0.67 +/- 0.19 [four of six patients]; P =.02). Ten of 15 patients treated with chemotherapy, including four of six stage II to III patients, are alive after a median follow-up of 33 months. CONCLUSION: On the basis of a standardized clinical and histopathologic assessment, risk-adapted therapeutic strategies for OSCST can be evaluated. Considering our experience, we would recommend that stage IA tumors be followed up at regular intervals, whereas we would recommend cisplatin-based chemotherapy in stage IC tumors with preoperative rupture or malignant ascites, especially those with high mitotic activity. Finally, cisplatin-based chemotherapy also seems to be effective in advanced-stage tumors.     

Contribution of lymph node staging method and prognostic factors in malignant ovarian sex cord-stromal tumors: A world wide database analysis

Objective

To investigate the clinicopathologic prognostic factors in patients with malignant sex cord-stromal tumors (SCSTs) with lymph node dissection, and at the same time, to evaluate the influence of the log odds of positive lymph nodes (LODDS) on their survival.

Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails.

PURPOSE: To assess the efficacy and toxicity of the marine-derived alkaloid trabectedin (ET-743) in patients with advanced ovarian cancer refractory to or experiencing disease relapse after platinum- and taxane-based chemotherapy. PATIENTS AND METHODS: Fifty-nine patients from four institutions either resistant (n = 30) or sensitive (n = 29) to prior platinum and taxanes were treated with a 3-hour infusion of trabectedin every 3 weeks. Patients were monitored weekly for toxicity and restaged every two cycles for response. Response was assessed according to Response Evaluation Criteria in Solid Tumors Group. RESULTS: The peer-reviewed objective response rate in platinum-sensitive patients was 43% (95% CI, 23% to 65%) with an estimated median time to progression of 7.9 months (95% CI, 7.5 to 14.1 months); in platinum-resistant patients two partial responses were observed. Responses were durable for up to 12.9 months (median, 5 months). The predominant toxicities at the recommended dose of 1,300 microg/m(2) were neutropenia, asthenia, and self-limited increase of aminotransferases never requiring treatment interruption. CONCLUSION: Trabectedin administered as a 3-hour infusion at 1,300 microg/m(2) is a safe new drug with promising activity in relapsed ovarian cancer, showing a 43% objective response rate in patients with platinum-sensitive disease, which favorably compares with other salvage treatments and warrants additional development either alone or in combination.     

The treatment of advanced gastric cancer: new findings on the activity of the taxanes

Globally, gastric cancer is one of the most common types of cancer and one of the most frequent causes of cancer-related death. Despite many advances in the diagnosis and treatment of this disease, the prognosis for gastric cancer remains poor, especially in more advanced stages. In metastatic disease, benefits in survival and quality of life have been demonstrated in patients with unresectable or metastatic gastric cancer receiving chemotherapy plus best supportive care versus best supportive care alone. The taxanes, which are among the most promising cytotoxic agents in clinical use, have shown encouraging activity in early-phase studies as single agents and in combination regimens in the treatment of advanced gastric cancer. Recently, interim results of a randomized phase III trial comparing the triplet of docetaxel, cisplatin, and 5-fluorouracil with a standard reference regimen of cisplatin and 5-fluorouracil were reported. Patients treated with the docetaxel-containing regimen had a statistically superior response rate and time to disease progression as well as a clinically significant prolongation of survival. This study underscores the importance of developing new therapeutic options for patients with advanced gastric cancer.     

The role of taxanes in the treatment of metastatic melanoma

The management of patients with metastatic malignant melanoma remains difficult. Conventional chemotherapy has been disappointingly ineffective. Dacarbazine (DTIC) is considered to be one of the most active single agents with a response rate of approximately 15-20%. Many patients who initially respond to treatment subsequently relapse. Clearly, there is a need for improvement, and the evaluation of new agents is warranted. This article reviews current phase II studies of single-agent taxanes and their combinations in patients with metastatic melanoma, and examines the likely impact of taxanes on treatment strategies. Response rates from phase II trials with single-agent taxanes vary from 3.3% to 17%. Prolonged durations of disease control are observed. Combinations of taxanes with DTIC, temozolomide, cisplatin, carboplatin and tamoxifen have demonstrated response rates from 12% to 41%, suggesting that they are at least as effective as various other combination regimens. Encouraging results have been produced in the second-line metastatic setting. Taxanes, both as single agents and in combinations, may be a treatment option for some patients with metastatic melanoma, especially in the second-line setting.     

Ifosfamide in the treatment of malignant epithelial ovarian tumors

Ifosfamide is one of the best-known alkylating agents. In advanced epithelial ovarian cancer, it has been tested in association with cisplatin, achieving results equal, if not better than cyclophosphamide, with acceptable toxicity. In second-line therapy, it shows remarkable activity, even in patients refractory to cisplatin already treated with cyclophosphamide, with more severe, but always manageable toxicity. In gynecological sarcomas, ifosfamide is, together with doxorubicin, the reference drug for chemotherapy.     

Contemporary treatment of borderline ovarian tumors

In conclusion, the prognosis for women with stage I borderline tumors is excellent. Surgery alone is the recommended treatment. For young patients, fertility-sparing surgery is optimal, with a small percentage eventually developing tumor in the contralateral ovary. For patients with advanced stage borderline tumors, 10-30% will relapse and approximately 10% will die of tumor. This risk is clearly higher for those with invasive peritoneal implants. Several controversies exist, including the classification of advanced stage serous borderline tumors and the issue of postoperative treatment. Future studies involving larger series and molecular biomarkers will hopefully elucidate the biologic behavior and optimal therapy for this interesting group of tumors.     

Radiation in multidisciplinary treatment of children with malignant ovarian tumors.

Thirteen girls with malignant ovarian tumors treated at Memorial Hospital from August 1971 through October 1975 with extensive surgery, multi-drug chemotherapy (T-2 protocol) and postoperative radiation were reviewed. The plan of radiation was to deliver 3,000 rads to the whole abdomen and boost the para-aortic and pelvic area with 1,500 rads in five to six weeks. In only two patients was the radiation conducted as planned. In others the treatment was either interrupted or discontinued due to complications. Four of the thirteen patients are dead. The cause of death in two of these patients was distant metastases; the two other patients died without evidence of tumor due to treatment complications. Three of the nine patients who are alive without evidence of disease have late complications. Following radical surgery, lower doses of radiation given concomitantly with T-2 protocol chemotherapy seem to be sufficient for controlling the disease.     

卵巢恶性肿瘤相关危险因素分析

对３９６例卵巢包块病人进行回顾性分析，结果发现，恶性肿瘤６５例（１６％），良性肿瘤１５９例（４０％），子宫内膜异位囊肿１３０例（３３％），生理性囊肿２０例（５％），炎性包块７例（１％）。４０岁以上妇女卵巢恶性肿瘤的相对危险性显著增加（Ｐ〈０．００１），腹水、腹胀、泌尿道症状和体重，食欲降低是恶性肿瘤的重要危险因素。超声影像混合性包块与恶性肿瘤明显相关。     

紫杉类药物在乳腺癌治疗中的耐药机制

目前研究提示紫杉类耐药可能与多药耐药相关蛋白(MRP)表达增高、Ⅲβ-微管过表达、微管相关蛋白tau的过表达有关,而与HER2的表达成负相关.针对这些耐药靶点可逆转或者延缓紫杉类药物耐药的发生,为临床上更好地使用紫杉类药物提供一定参考.     

Intraperitoneal chemotherapy with taxanes for ovarian cancer with peritoneal dissemination.

Paclitaxel and docetaxel are currently the two clinically available taxanes. The combination of a taxane and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer. Despite the high activity of these drugs in systemic chemotherapy, the majority of patients with advanced ovarian cancer will develop recurrent disease and ultimately decease of this disease. Therefore, more effective systemic chemotherapy regimens or alternative treatment modalities are warranted. Intraperitoneal chemotherapy is such an alternative treatment option. Pharmacokinetic studies on intraperitoneal administration of paclitaxel and docetaxel demonstrated very high locoregional drug concentrations and exposure. Their activity and response seem to be dose-dependent and hence higher efficacy with limited systemic toxicity is to be expected. Intraperitoneal chemotherapy may be combined intraoperatively with hyperthermia, which enhances tissue penetration and cytotoxic activity of many drugs. The data concerning thermal enhancement of taxanes are inconsistent, but at the high locoregional concentrations provided by intraperitoneal drug administration such a thermal enhancement seems to exist. Clinical studies have clearly demonstrated the feasibility and efficacy of intraperitoneal instillation chemotherapy with taxanes in patients with ovarian cancer. Preliminary results of a phase III study demonstrated improved outcome with the addition of intraperitoneal instillation chemotherapy to systemic chemotherapy after optimal primary cytoreductive surgery. Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel has been performed in a single study, in which promising results were observed. Further clinical investigations with an adequate follow-up period are needed to confirm the promising initial results and to determine the exact efficacy of intraperitoneal chemotherapy with these drugs.     

The taxanes: toxicity and quality of life considerations in advanced ovarian cancer

The taxanes paclitaxel and docetaxel show good activity in the management of advanced ovarian cancer when used in conjunction with platinum agents. Accumulating evidence from clinical studies, particularly the latest results from the phase III comparative SCOTROC study, indicates that the two drugs confer similar rates of tumour response and survival in women with this condition. However, it is clear that paclitaxel and docetaxel differ in their tolerability profiles and in other respects, and cannot be regarded as directly equivalent drugs. In particular, paclitaxel is associated with significant neurotoxicity; peripheral neuropathy has also been reported with docetaxel, but to a lesser extent. Neutropenia appears more prevalent with docetaxel than with paclitaxel, although clinical trial data show that this adverse effect is manageable and need not compromise dose delivery. Docetaxel is also associated with potential benefits accruing from shorter infusion times and lack of need for premedication with intravenous histamine H(1) and H(2) antagonists. Emerging quality of life data are expected to shed further light on the overall benefit of chemotherapy in women with advanced ovarian cancer in general, and on taxane-platinum combinations in particular.     

Treatment of malignant ovarian germ cell tumor and sex cord tumors

We outline chemotherapy mainly for malignant ovarian germ cell and sex-cord tumors, based on studies in the literature and our own clinical experiences. With both tumors, PEB treatment is standard adjuvant chemotherapy. With regard to the number of dosage courses, 4 courses are regarded as tolerable after incomplete reduction, and 3 courses as adjuvant treatment after complete extraction. This chemotherapy is effective for preservation of fertility in young patients with malignant ovarian germ cell tumor. In both tumors, some cases show chemotherapy resistance. An effective second-line treatment strategy using a new anticancer agent needs to be established for such cases in the future.     

The plasminogen-activation system in ovarian tumors

We studied the plasminogen activation system in tumor tissue by measuring the antigen level of the 2 plasminogen activators, tissue-type (t-PA) and urokinase-type (U-PA) and their inhibitors, plasminogen-activator inhibitors type-1 (PAI-1) and type-2 (PAI-2) in the tissue extracts of 43 human benign and malignant ovarian tumors. U-PA levels were significantly higher in malignant than in benign tumors. In addition, U-PA antigen levels were higher in the metastatic tissue of advanced disease (FIGO stage III) than in the primary localized tumor (FIGO stage I/II). Also PAI-1 concentrations tended to be higher in malignant than in benign tumors, but this difference was not statistically significant. In contrast, t-PA levels were lower in metastatic than in non-metastatic tumors, whereas PAI-2 levels were unrelated to the stage of ovarian malignancy. These results were integrated in a plasminogen-activation-dependent malignancy index (U-PA × PAI-1/t-PA). This index distinguished the different groups of benign ovarian tumors, localized and metastatic ovarian carcinomas better than U-PA levels. It could be useful as a prognostic indicator in ovarian cancer © 1993 Wiley-Liss, Inc.