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Advanced Ovarian Cancer (advanced + ovarian_cancer)
Selected AbstractsAlternate delivery route for amifostine as a radio-/chemo-protecting agentJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2008Natalie P. Praetorius Amifostine (ethiofos, WR-2721) is an organic thiophosphate prodrug that serves as an antineoplastic adjunct and cytoprotective agent useful in cancer chemotherapy and radiotherapy. The selective protection of certain tissues of the body is believed to be due to higher alkaline phosphatase activity, higher pH and vascular permeation of normal tissues. Amifostine is conventionally administered intravenously before chemotherapy or radiotherapy. It is approved by the Food and Drug Administration (FDA) to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. It was originally indicated to reduce the cumulative renal toxicity from cisplatin in non-small cell lung cancer although this indication was withdrawn in 2005. Amifostine is also FDA approved for patients with head and neck cancer to reduce the incidence of moderate to severe xerostomia in patients who are undergoing postoperative radiation treatment where the radiation port includes a substantial portion of the parotid glands. The potential of amifostine as a cytoprotective agent is unlikely to be fully realized if the method of administration is restricted to intravenous administration. Attempts have been made to develop non-invasive methods of delivery such as transdermal patches, pulmonary inhalers, and oral sustained-release microspheres. It is the goal of this article to explore non-intravenous routes of administration associated with better efficacy of the drug. This review will primarily focus on the variety of more recently studied (2002 and later) alternative modes for amifostine administration, including subcutaneous, intrarectal and oral routes. [source] The role of neoadjuvant chemotherapy in treating advanced epithelial ovarian cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010Lori E. Weinberg MD Abstract The current management of advanced ovarian cancer consists of aggressive primary cytoreductive surgery (PCS) followed by combination platinum based chemotherapy. Recent studies have suggested that platinum-based chemotherapy may be of benefit in patients with advanced ovarian cancer prior to cytoreductive surgery (neoadjuvant chemotherapy, NACT). The concept of NACT has not been completely validated in the treatment of ovarian cancer. This review will discuss the role of NACT in patients with advanced epithelial ovarian cancer. J. Surg. Oncol. 2010; 101:334,343. © 2010 Wiley-Liss, Inc. [source] Cytoreductive surgery and intraoperative hyperthermic chemoperfusion for advanced ovarian carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2005Trevor W. Reichman MD Abstract Background Optimal cytoreductive surgery combined with intraoperative hyperthermic chemoperfusion (IHCP) is a therapy that potentially could improve survival in a select group of patients with advanced ovarian cancer. The purpose of this study was to review the results of cytoreductive surgery and IHCP for advanced ovarian cancer and to identify factors that may predict which patients maximally benefit from this aggressive treatment. Methods Patients treated with cytoreduction followed by IHCP for ovarian cancer were identified from an IHCP database from 1/2001 through 3/2004. Several factors including resection status, peritoneal cancer index (PCI), and prior surgery were evaluated for their ability to predict survival in our cohort of patients. Results Thirteen patients with ovarian cancer treated with cytoreductive surgery followed by IHCP were identified. The 3-year overall survival rate for all thirteen patients was 55%. The median disease-free survival was 15.4 months (3-year disease-free survival, 11%). Several factors including PCI score (<6), ability to resect all gross disease, and previous surgical exploration appeared to impart an overall survival advantage. Conclusions The use of IHCP coupled with optimal cytoreduction is a safe and effective treatment for advanced ovarian carcinoma. However, the proper selection of patients who will benefit most from the therapy is essential for the success of the treatment. J. Surg. Oncol. 2005;90:51,56. © 2005 Wiley-Liss, Inc. [source] Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling,MOLECULAR CARCINOGENESIS, Issue 1 2010Jane L. Watson Abstract New cytotoxic agents are urgently needed for the treatment of advanced ovarian cancer because of the poor long-term response of this disease to conventional chemotherapy. Curcumin, obtained from the rhizome of Curcuma longa, has potent anticancer activity; however, the mechanism of curcumin-induced cytotoxicity in ovarian cancer cells remains a mystery. In this study we show that curcumin exhibited time- and dose-dependent cytotoxicity against monolayer cultures of ovarian carcinoma cell lines with differing p53 status (wild-type p53: HEY, OVCA429; mutant p53: OCC1; null p53: SKOV3). In addition, p53 knockdown or p53 inhibition did not diminish curcumin killing of HEY cells, confirming p53-independent cytotoxicity. Curcumin also killed OVCA429, and SKOV3 cells grown as multicellular spheroids. Nuclear condensation and fragmentation, as well as DNA fragmentation and poly (ADP-ribose) polymerase-1 cleavage in curcumin-treated HEY cells, indicated cell death by apoptosis. Procaspase-3, procaspase-8, and procaspase-9 cleavage, in addition to cytochrome c release and Bid cleavage into truncated Bid, revealed that curcumin activated both the extrinsic and intrinsic pathways of apoptosis. Bax expression was unchanged but Bcl-2, survivin, phosphorylated Akt (on serine 473), and total Akt were downregulated in curcumin-treated HEY cells. Curcumin also activated p38 mitogen-activated protein kinase (MAPK) without altering extracellular signal-regulated kinase 1/2 activity. We conclude that p53-independent curcumin-induced apoptosis in ovarian carcinoma cells involves p38 MAPK activation, ablation of prosurvival Akt signaling, and reduced expression of the antiapoptotic proteins Bcl-2 and survivin. These data provide a mechanistic rationale for the potential use of curcumin in the treatment of ovarian cancer. © 2009 Wiley-Liss, Inc. [source] Effect of a combination of extract from several plants on Cell-mediated and humoral immunity of patients with advanced ovarian cancerPHYTOTHERAPY RESEARCH, Issue 5 2006N. Kormosh Abstract The influence of a plant preparation AdMax (Nulab Inc., Clearwater, FL, USA) on immunity in ovarian cancer patients was studied. The preparation is a combination of dried ethanol/water extracts from roots of Leuzea carthamoides, Rhodiola rosea, Eleutherococcus senticosus and fruits of Schizandra chinensis. Twenty eight patients with stage III,IV epithelial ovarian cancer were treated once with 75 mg/m2 cisplatin and 600 mg/m2 cyclophosphamide. Peripheral blood was collected 4 weeks after the chemotherapy. Subclasses of T, B and NK lymphocytes were tested for in the blood samples: CD3, CD4, CD5, CD7, CD8, CD11B, CD16, CD20, CD25, CD38, CD45RA, CD50, CD71 and CD95. Immunoglobulin G, A and M concentrations were also determined. Changes were observed in the following T cell subclasses: CD3, CD4, CD5 and CD8. In patients who took AdMax (270 mg a day) for 4 weeks following the chemotherapy, the mean numbers of the four T cell subclasses were increased in comparison with the mean numbers of the T cell subclasses in patients who did not take AdMax. In patients who took AdMax, the mean amounts of IgG and IgM were also increased. The obtained results suggest that the combination of extracts from adaptogenic plants may boost the suppressed immunity in ovarian cancer patients who are subject to chemotherapy. Copyright © 2006 John Wiley & Sons, Ltd. [source] Intraperitoneal chemotherapy for advanced epithelial ovarian malignancy: Lessons learnedAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2009Michael BUNTING Background:, The administration of intraperitoneal (IP) chemotherapy as first-line adjuvant treatment for women with optimally debulked advanced ovarian malignancy results in improved median and overall survival when compared with intravenous (IV) chemotherapy. However, the number of adverse events and toxicities are increased in patients treated with IP chemotherapy. In addition, the administration of IP chemotherapy is technically more challenging and the schedule is more demanding in terms of time and resources. Aims:, We report on our initial experience with the administration of IP chemotherapy at two gynaecological oncology units in Australia. Methods:, We collected retrospective data from a series of 23 women undergoing IP chemotherapy as adjuvant treatment for advanced ovarian cancer. In addition to standard (Common Terminology Criteria for Adverse Events v3.0, CTCAE) toxicity data, we collected technical data specific to the administration of IP chemotherapy. Results:, The average number of IP chemotherapy cycles received was 4.3. Forty-three per cent of patients received all six planned IP chemotherapy cycles. Thirty-nine per cent of patients discontinued their IP treatment. Of those, 22% were discontinued because of drug-related toxicities and the remaining 17% experienced a port complication or toxicity directly related to the route of administration. Conclusions:, This study demonstrates the feasibility and practicality of and lessons learned from initial experiences with IP chemotherapy for ovarian cancer in Australia. [source] Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum-paclitaxel chemotherapy,CANCER, Issue 6 2010Aristotle Bamias MD Abstract BACKGROUND: Mucinous and clear cell histology have been associated with adverse prognosis in ovarian carcinomas. The authors compared the outcome of these subtypes with that of serous tumors in patients who were treated with combination paclitaxel/platinum at their center. METHODS: Four hundred twenty patients with histologically confirmed, serous (n = 367), mucinous (n = 24), or clear cell (n = 29) ovarian carcinomas, International Federation of Gynecology and Obstetrics stage III or IV disease, and who were treated with paclitaxel/platinum after cytoreductive surgery were included in this analysis. RESULTS: The median overall survival for each histological subtype was 47.7 months (95% confidence interval [CI], 37.7-57.7 months) for serous, 15.4 months (95% CI, 4.2-26.6 months) for mucinous, and 36.6 months (95% CI, 22.7-50.5 months) for clear cell carcinomas. Cox regression analysis showed that mucinous histology was an independent predictor of poor prognosis compared with serous tumors (hazard ratio, 0.360; 95% CI, 0.215-0.603; P = .001). In contrast, such a difference between clear cell and serous carcinomas was not found (P = .337). Median survival of patients with mucinous tumors and residual disease >2 cm was poor, averaging 7.1 months (95% CI, 4.6-9.6 months). CONCLUSIONS: Mucinous but not clear cell histology is associated with significantly worse prognosis in advanced ovarian cancer treated with combination platinum/paclitaxel. Different therapeutic strategies should be studied in this entity. Cancer 2010. © 2010 American Cancer Society. [source] Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trialsCANCER, Issue 6 2009By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR), the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO) Abstract BACKGROUND: Primary surgery followed by platinum-taxane based chemotherapy has been the standard therapy in advanced ovarian cancer. However, the prognostic role of complete and so-called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined. METHODS: Exploratory analysis was conducted of 3 prospective randomized trials (AGO-OVAR 3, 5, and 7) investigating platinum-taxane based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002. RESULTS: A total of 3126 patients were analyzed. Approximately one-third each fulfilled criteria for complete resection (group A), small residual tumor burden of 1-10 mm (group B), or macroscopic residual disease exceeding 1 cm in diameter (group C). Multivariate analysis showed improved progression-free and overall survival for group A with complete resection compared with groups B or C (P < .0001). The impact of so-called optimal debulking as in group B showed a smaller prognostic impact compared with group C. Further independent prognostic factors for overall survival were age, performance status, grade, FIGO stage, and histology, namely the mucinous subtype. An interaction between residual tumor and some biologic factors was demonstrated. CONCLUSIONS: The goal of primary surgery should be complete resection. The prognostic impact of tumor biology seemed to be partially overruled by residual tumor and further evaluation of biologic factors should stratify for residual tumor. Cancer 2009. © 2009 American Cancer Society. [source] Psychosocial factors and interleukin-6 among women with advanced ovarian cancerCANCER, Issue 2 2005Erin S. Costanzo M.A. Abstract BACKGROUND Relations among psychological stress, depression, social support, and interleukin-6 (IL-6, a proinflammatory cytokine) have been documented in humans and animals. Because elevated IL-6 is associated with a poorer prognosis among ovarian cancer patients and has been implicated in the metastasis of ovarian cancer, the current study examined relations between psychosocial factors and IL-6 among women with advanced-stage ovarian cancer. METHODS Sixty-one ovarian cancer patients completed assessments of social support, distressed mood, and quality of life before surgery. Peripheral blood was drawn preoperatively, and the plasma was assayed for IL-6. Ascites samples were also assayed for IL-6 for a subset of patients. RESULTS Both IL-6 levels and distressed mood were elevated among patients. After statistically adjusting effects of age and disease stage, social attachment was associated with lower levels of IL-6 in peripheral blood (P = 0.03), whereas poorer health-related quality of life was associated with higher IL-6 (P values ranged from 0.01 to 0.03 on different measures). This pattern of relations was also found in the ascites. Moreover, IL-6 levels in peripheral blood plasma correlated significantly with IL-6 in the ascites (P < 0.001), suggesting that peripheral IL-6 reflects IL-6 levels at the site of the tumor. CONCLUSIONS Results suggest that social support may play a protective role with respect to IL-6 elevations, and IL-6 may be an independent marker of health-related quality of life among ovarian cancer patients. Processes involving IL-6 represent possible pathways by which behavioral factors may contribute to disease outcomes among women with ovarian cancer. Cancer 2005. © 2005 American Cancer Society. [source] | ||||||||||