Docetaxel and ovarian cancer

Docetaxel has exhibited substantial clinical activity against platinum, refrac- tory, paclitaxel resistant and previously untreated advanced ovarian cancer. As single agent, in advanced ovarian cancer patients previously treated with platinum agents, docetaxel 100 mg/m(2) every 3 weeks yields a 30% overall response rate and 6 months duration of response. In vitro data demonstrate a lack of complete cross-resistance bet- ween docetaxel and paclitaxel. In both platinum- and paclitaxel-pretreated patients, the highest response rates were obtained in patients with the longest interval of time since receipt of prior chemotherapy. Docetaxel currently is being intensively evaluated as a component of first line combination chemotherapy for ovarian cancer. Phase I-II have shown that docetaxel-platinum doublets are feasible and highly effective in the treatment of ovarian cancer, with docetaxel-carboplatin providing a more favorable safety profile compared with docetaxel-cisplatin, particularly with respect to neurotoxicity. The preliminary results of a phase III comparison of docetaxel-carboplatin versus paclitaxel-carboplatin support the clinical use of docetaxel-carboplatin as first line chemotherapy for stage IC to IV ovarian cancer, as it was shown to reduce the incidence of grade > 2 neurosensory toxicity compared to paclitaxel-carboplatin. Comparative overall survival and quality of life and more mature progression free survival data will be instrumental in determining the relative merits of docetaxel-carboplatin and paclitaxel-carboplatin as first line adjuvant therapy for ovarian cancer. The positive clinical experiences with docetaxel-provide a strong basis for continued investigation of docetaxel-carboplatin-based chemotherapy as component of advanced ovarian cancer management.     

Docetaxel and carboplatin for epithelial ovarian cancer

We report herein on the efficacy and toxicity of docetaxel and carboplatin in patients with epithelial ovarian cancer. Fifteen patients with FIGO stage I c-IV epithelial ovarian cancer were administered docetaxel (70 mg/m2) and carboplatin (AUC 5) every 3 weeks as 1 course. Eleven patients received this regimen as a first-time chemotherapy, and the other 4 as therapy for recurrence. Seven patients were evaluated for response. Of these, 6 achieved complete response and the other a partial response. CA 125 response was seen in 2 of 8 patients who did not have visible tumors. Our toxicity findings include the following: grade 3 and 4 neutropenia (86.7%), hypersensitive reaction (13.3%), grade 2 alopecia (13.3%), and no edema. Docetaxel and carboplatin are actively used in ovarian cancer, with the major toxicity being bone marrow suppression. But we were able to control myelosuppression with G-CSF. Hypersensitivity reactions were frequent, we thought pre-medication. This chemotherapy combination appears effective for epithelial ovarian cancer.     

Docetaxel: an alternative taxane in ovarian cancer

The taxanes paclitaxel and docetaxel are potent chemotherapeutic agents that block tubulin depolymerisation, leading to the inhibition of microtubule dynamics and cell cycle arrest. Although docetaxel and paclitaxel share a mutual tubulin binding site, mechanistic and pharmacological differences exist between these agents. For example, docetaxel has increased potency and an improved therapeutic index compared with paclitaxel, and its short 1-h infusion offers a substantial clinical advantage over the prolonged infusion durations required with paclitaxel. In clinical studies, docetaxel monotherapy demonstrated good response rates and an acceptable toxicity profile in both paclitaxel- and platinum-refractory ovarian cancer patients. In particular, neurotoxicity - a dominant side effect with both paclitaxel and cisplatin - occurs at a low incidence with docetaxel, making docetaxel a promising agent for combining cisplatin and other platinum compounds. In Phase II studies, the combination of docetaxel with either cisplatin or carboplatin has yielded impressive response rates of 69-74 and 81-87%, respectively. Furthermore, Phase III data suggest that docetaxel-carboplatin and paclitaxel-carboplatin are similarly efficacious with respect to progression-free survival and clinical response, although neurotoxicity occurs more frequently with the paclitaxel regimen. While paclitaxel-carboplatin remains the standard treatment for the management of advanced ovarian cancer, docetaxel-carboplatin appears to be a promising alternative, particularly in terms of minimising the incidence and severity of peripheral neuropathy.     

Docetaxel: promising and novel combinations in ovarian cancer

Despite considerable progress over the past two decades in the management of advanced ovarian cancer, the majority of patients with this type of malignancy still die from their disease, and the search for new and improved first-line and salvage chemotherapy regimens continues. As part of this work, the antitumour activity and effect on survival of new chemotherapy combinations containing the novel taxane docetaxel are being explored. Dual therapy with docetaxel plus a camptothecin (a topoisomerase inhibitor) has shown promise in second-line treatment, and preliminary data indicate good activity of docetaxel in combination with gemcitabine. Triple-therapy studies have produced mixed results, but encouraging activity has been reported when the anthracycline, epirubicin, is added to docetaxel and carboplatin - sequential therapy with docetaxel, cisplatin and epirubicin is currently being assessed. Combinations of docetaxel, carboplatin and gemcitabine may also be of future interest. Early efficacy and tolerability results with novel combination chemotherapy regimens involving docetaxel thus offer the promise of additional progress in the chemotherapy of advanced ovarian cancer, and further trials should be encouraged.     

Surgical standards in the management of ovarian cancer

Surgery is the cornerstone of management of epithelial ovarian cancer and has broad applications throughout the clinical course of disease, from initial diagnosis to palliative care. Comprehensive surgical staging is essential for precise prognostic determination and treatment planning for patients with apparent early-stage ovarian cancer. Although randomized trials are lacking, the survival advantage associated with optimal primary cytoreduction has been consistent and reproducible. With increasing radicality of cytoreductive surgical techniques and sophistication of postoperative care, it appears that an "optimal" surgical procedure is that which leaves the patient with no visible residual disease. The survival benefits of cytoreductive surgery are also applicable to women with stage IV ovarian cancer, although the rate of success is somewhat attenuated compared with patients with stage III disease. Recent data also indicate that with appropriate surgical selection criteria, secondary cytoreduction is associated with a significant prolongation of survival for patients with recurrent ovarian cancer. Unfortunately, several recent publications illustrate how the decentralization of health care may have significant ramifications on the ability of women with known or suspected ovarian cancer to avail themselves of the surgical standard of care.     

Future directions in the management of ovarian cancer

As investigators at the bench define the oncogenic pathways involved in ovarian cancer growth and invasion, clinical scientists will develop therapies to target these important pathways. The approach to the treatment of ovarian cancer will change to focus on strategies designed to eliminate minimal residual disease after primary therapy and in this way cure the disease. Concepts of consolidation after standard adjuvant chemotherapy and maintenance regimens will start to be evaluated for clinical efficacy. In addition, the focus on recurrent disease may change from repeated cytotoxic approaches to regimens chosen to prevent invasion or the development of drug resistance, changing the approach to ovarian cancer recurrence to a treatment plan of managing a chronic, but not imminently terminal, disease.     

Cytoreductive surgery in the management of ovarian cancer

The standard management for previously untreated advanced-stage epithelial ovarian cancer is optimum cytoreductive surgery followed by aggressive cytotoxic chemotherapy. This approach is based on a retrospective review of a single-institution experience published more than 30 years ago and has yet to be confirmed in a prospective randomized trial. Many subsequent studies have supported the observation that advanced ovarian cancer patients who have the longest survival invariably have no macroscopic disease left at the completion of the initial surgery. The combination of a platinum- and taxane-based chemotherapy regimen is now well established as the most active one for treating women with advanced ovarian cancer. However, the overwhelming majority of patients with advanced ovarian cancer will eventually experience disease recurrence and develop resistance to cytotoxic chemotherapy. Selected patients with recurrent ovarian cancer--ie, those with an isolated recurrence identified more than 6 months following completion of initial chemotherapy and who have an excellent performance status--are managed with cytoreductive surgery followed by a platinum-based regimen. As in previously untreated patients, patients who have no macroscopic residual tumor left after secondary debulking for recurrent ovarian cancer have a significantly better survival than those left with any gross tumor. This article will review the role of surgery in the initial management of advanced-stage and recurrent ovarian cancer, focusing on the definition of optimum surgical cytoreduction.     

Update on the management of ovarian cancer

Ovarian cancer remains the leading gynecologic cause of death in the United States and the Western world. Progression to metastatic disease prior to diagnosis contributes to the high mortality rate associated with ovarian cancer. The current article reviews surgical and drug therapies for ovarian cancer. Prognostic factors and preventative treatment are also discussed. Surgery is essential for accurate staging of ovarian cancer and treatment. Cytoreduction, combined with chemotherapy, may relieve symptoms associated with bowel obstruction and improve survival. Management of early-stage ovarian cancer depends upon risk status determined via comprehensive staging at the time of surgical resection. High-risk, but not low-risk, patients require adjuvant chemotherapy. Studies comparing various combinations of cytotoxic agents for the treatment of advanced stage ovarian cancer are described. Despite surgery and chemotherapy, ovarian cancer recurs in approximately 50% of patients. Management of recurrent ovarian cancer and maintenance therapy following remission are discussed.     

Role of chemotherapy in the management of ovarian cancer

Ovarian cancer is a highly chemotherapy-sensitive malignancy. With current treatment, most women presenting with advanced disease will achieve an objective response and experience major and sustained improvement of cancer-related symptoms. Unfortunately, the majority of patients will ultimately recur, such that second-line treatment options will need to be considered. Further complicating the decision-making process in choosing an ‘optimal’ second-line regimen is a serious paucity of randomized trials in this clinical setting.     

Role of chemotherapy in the management of ovarian cancer

Ovarian cancer is a highly chemotherapy-sensitive malignancy. With current treatment, most women presenting with advanced disease will achieve an objective response and experience major and sustained improvement of cancer-related symptoms. Unfortunately, the majority of patients will ultimately recur, such that second-line treatment options will need to be considered. Further complicating the decision-making process in choosing an 'optimal' second-line regimen is a serious paucity of randomized trials in this clinical setting.     

多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌

目的探讨多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌患者的临床疗效。方法选取2011年1月至2012年12月收治的80例晚期卵巢癌患者为研究对象,依据随机数字法分为试验组和对照组。对照组给予多西他赛联合腹腔热灌注化疗,试验组在对照组的治疗基础上给予热疗,观察两组患者的临床疗效和不良反应。结果试验组总有效率(82.5%)显著高于对照组总有效率(60.0%),两组差异有统计学意义(P<0.05)。试验组白细胞减少、恶心与呕吐、消化道反应、肝功能损害的发生率均低于对照组,差异均有统计学意义(均P<0.05)。结论应用多西他赛联合腹腔热灌注化疗加热疗治疗晚期卵巢癌可提高临床疗效,不良反应少,治疗安全性高,值得临床应用。     

Docetaxel in combination with irinotecan (CPT-11) in platinum-resistant paclitaxel-pretreated ovarian cancer

The role of combination chemotherapy regimens in the management of ovarian cancer patients with tumors resistant to platinum compounds has not yet been defined. This multicenter prospective phase II study evaluated the activity and toxicity of the docetaxel-plus-irinotecan combination in ovarian cancer patients whose tumors were resistant to platinum compounds and who had been exposed to paclitaxel. Treatment consisted of docetaxel 60 mg/m2 i.v. followed by irinotecan 200 mg/m2 i.v. both on day 1 followed by prophylactic recombinant human granulocyte-colony stimulating factor (rhG-CSF) support from days 2 to 6, every 3 weeks. Thirty-one patients were enrolled in the study. The median age was 60 years, and the median performance status (ECOG) was 1. Eight (26%) patients had primary tumors resistant to platinum, while the rest of the population had tumor recurrence within 6 months from the last cisplatin treatment. Four chemotherapy cycles per patient were administered, with the delivered dose intensity at 75% of the planned dose for both agents. Among 30 patients evaluable for response, there were 2 (7%) complete and 4 (14%) partial responses (overall response rate 20%; (95% confidence interval, CI, 11%-33%). Stable disease was recorded in 8 (28%) patients and progressive disease in 15 (51%). The median response duration was 4.5 months (range, 3-12), the median time to progression 5 months (range, 2-17) and the median survival 11 months (range, 1-40); the 1-year survival was almost 50%. Myelotoxicity was moderate, with grade 3 and 4 neutropenia occurring in 23% of the patients, grade 3-4 thrombocytopenia in 6% and febrile neutropenia in 13%. Grade 3 diarrhea was observed in 2% of the patients. There was one treatment-related death due to sepsis. In conclusion, the combination of docetaxel plus irinotecan with rhG-CSF support, appears to be a moderately effective regimen with acceptable toxicity for platinum-resistant, paclitaxel-pretreated ovarian cancer patients. Further investigation in comparative studies is required to define the role of combination versus single agent chemotherapy in this group of patients.     

Future directions in the management of epithelial ovarian cancer

Epithelial ovarian cancer can be a difficult malignancy to manage, partially owing to its heterogenous biology. Whilst desirable, screening designed to reduce mortality has not yet proven effective, though results of ongoing studies are awaited. In this brief review, we attempt to highlight some important issues in the current management of primary and recurrent ovarian cancer, and to place these issues in the context of cutting-edge approaches to targeted therapy and its combination with chemotherapy, as well as other novel treatment strategies. It is hoped that this will lead to further improvements in progression-free and overall survival for patients with ovarian cancer, whilst maintaining their quality of life for as much of the disease journey as possible.     

Docetaxel in gastric cancer

Patients with advanced gastric cancer have a poor prognosis. 5-Fluorouracil (F) and cisplatin (C) based regimens are often considered to be reference regimens in the treatment of patients with advanced gastric cancer. Best supportive care in advanced gastric carcinoma results in median survival times of 3–4 months. Docetaxel (D) plus cisplatin and 5-fluorouracil was selected by an Independent Data Monitoring Committee as the test regimen for the second (phase III) stage of the V325 study on the basis of the response rate in the randomised phase II first stage. Chemotherapy–naı̈ve patients were randomised to receive either DCF or CF. Tumour assessments were independently reviewed. At a planned interim analysis on 223 patients (111 DCF/112 CF) both the median time to progression and overall response rate were statistically superior in the DCF arm (5.2 months versus 3.7 months, and 39% versus 23%, respectively). The increase in median survival, 10.2 months compared with 8.5 months in this interim analysis did not yet reach statistical significance. The results of the full study population are awaited eagerly.     

The surgical management of ovarian cancer

This article aims to cover current concepts and controversies in the surgical management of ovarian cancer. While there have been significant advances in the surgical management of vulval, cervical and even endometrial cancer there have been few developments in the surgical management of ovarian cancer. This situation is likely to continue until we get a clearer understanding of the natural history of this disease and better therapeutic options become available.     

Surgical management of ovarian cancer.

Ovarian cancer affects over 25,000 women each year in the United States. The performance of appropriate surgery for ovarian cancer is critical in directing further therapies and improving survival. Systematic surgical staging must be performed in patients who appear to have early stage ovarian cancer because a significant proportion of these women have occult metastases. A marked improvement in survival has been demonstrated in patients with bulky disease if all masses larger than 2 cm can be surgically removed. Despite the dramatic effect of surgery on the subsequent course of the disease, recent studies show that only a minority of women with ovarian cancer receive appropriate initial surgery. We review the evidence and rationale for systematic surgical treatment of ovarian cancer.