-
The Cochrane Database of Systematic... Jan 2010Most patients with advanced ovarian cancer and some patients with advanced endometrial cancer need repeated drainage for malignant ascites. Guidelines to advise those... (Review)
Review
BACKGROUND
Most patients with advanced ovarian cancer and some patients with advanced endometrial cancer need repeated drainage for malignant ascites. Guidelines to advise those involved in the drainage of ascites are usually produced locally and are generally not evidence-based but mainly based on clinicians' anecdotal evidence and experience. To discover whether there are ways of managing drains that have been demonstrated to improve the efficacy and quality of the procedure is key in making recommendations which could improve the quality of life (QOL) for women at this critical period of their lives.
OBJECTIVES
To evaluate the benefit and harms of different practices in the management of drains for malignant ascites in the care of women with advanced or recurrent gynaecological cancer. The review aimed to evaluate the evidence regarding the following questions; How long should the drain stay in place? Should the volume of fluid drained be replaced intravenously? Should the drain be clamped to regulate the drainage of fluid? Should any particular vital observations be regularly recorded?
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2009, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE1950 to February Week 3 2009, Embase 1980 to 2009 Week 8 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs), quasi-RCTs and non-randomised studies that compared a range of interventions for management of multiple paracentesis in women with malignant ascites who had a confirmed histological diagnosis of gynaecological cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed.
MAIN RESULTS
The search strategy identified 1664 unique references of which 1646 were excluded on the basis of title and abstract. The remaining 18 articles were retrieved in full, but none satisfied the inclusion criteria.
AUTHORS' CONCLUSIONS
Since no relevant studies were identified, we are unable to make recommendations regarding the management of drains for malignant ascites in women with gynaecological cancer. Large, multi-centre RCTs are required to evaluate the efficacy and safety of the management of ascitic drains when in situ and their impact on QOL.
Topics: Ascites; Drainage; Female; Genital Neoplasms, Female; Humans
PubMed: 20091648
DOI: 10.1002/14651858.CD007794.pub2 -
Journal of Pain and Symptom Management Sep 2009The safety and efficacy of indwelling intraperitoneal (IP) catheters for the management of refractory malignant ascites is unclear. A systematic literature overview and... (Review)
Review
The safety and efficacy of indwelling intraperitoneal (IP) catheters for the management of refractory malignant ascites is unclear. A systematic literature overview and retrospective chart review of patients with malignant refractory ascites who underwent indwelling IP catheter placement was performed. Standardized literature abstraction and chart review templates were used to ensure that consistent information was collected. Fifteen publications met literature search criteria, representing 221 patients. Tenckhoff (Quinton Instrument Company, Seattle, WA, USA), Pleurex (Denver Biomedical Inc., Golden, CO, USA), and peritoneal catheters were used, along with IP ports. A median 5.9% of cases (range: 2.5%-34%) had documented peritonitis. In the literature, untunneled catheters were most commonly associated with infections. Our chart review added 19 cases from two academic institutions to this literature (median age: 60 years [range: 31-85]; females: 17 [89%]; gynecological malignancies: 14 [73%]). Palliative management before catheter placement included diuretics (n=4 [21%]) and multiple paracenteses (n=11 [58%] had two or more taps [range: 2-8]). Median time from diagnosis to catheter placement was 25 months (range: 1-77). Interventions were: French pigtail catheters (n=16 [84%]), Tenckhoff catheter (n=1 [5%]), and Port-A-Caths (Smith Medical MD, St. Paul, MN, USA) (n=2; 11%). Four (21%) catheters were tunneled. Prophylactic antibiotics were prescribed in six cases (32%). Two cases (11%) had documented infections, seven catheters (37%) became occluded, and two leaked (11%). The median time from catheter until death was 36 days (range: 4-660). Nine patients (47%) were admitted to hospice. In these retrospective studies, indwelling IP catheters appear to be a safe and effective palliative strategy to manage refractory malignant ascites, without overwhelming infection rates.
Topics: Adult; Aged; Aged, 80 and over; Ascites; Catheters, Indwelling; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Retrospective Studies
PubMed: 19328648
DOI: 10.1016/j.jpainsymman.2008.09.008 -
Health Technology Assessment... 2001Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the... (Comparative Study)
Comparative Study Review
BACKGROUND
Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the early stages of the disease, most cases are not detected until the advanced stages. Consequently, the prognosis after diagnosis is poor and the 5-year survival rate in the UK is only about 30%. Current recommendations suggest that first-line chemotherapy for ovarian cancer should involve paclitaxel and platinum (Pt)-based therapy (cisplatin/ carboplatin), however, most patients develop resistant or refractory disease and require second-line therapy. Patients may respond to re-challenge with Pt-agents if the treatment-free interval is > 6 months, but an alternative is often required. Topotecan is one of six drugs currently licensed in the UK for second-line therapy, and recent reviews suggest that it has modest efficacy in the treatment of advanced disease and performs favourably against paclitaxel. However, these reviews are based on a limited number of reports mainly consisting of non-randomised Phase I and II studies.
OBJECTIVES OF THE REVIEW
To examine the clinical effectiveness and cost-effectiveness of oral and intravenous topotecan (Hycamtin, SmithKline Beecham, UK) for the treatment of all stages of ovarian cancer.
SEARCH STRATEGY
Sixteen electronic databases from inception to September 2000 and Internet resources were searched, in addition to the bibliographies of retrieved articles and submissions from pharmaceutical companies.
INCLUSION AND EXCLUSION CRITERIA
Two reviewers independently screened all titles/abstracts and included/excluded studies based on full copies of manuscripts. Any disagreements were resolved through discussion. Only randomised controlled trials (RCTs) and full economic evaluations comparing topotecan to non-topotecan regimens were included. All stages of therapy and disease were considered, and the outcomes included were survival, response, symptom relief, quality of life, adverse effects and costs.
METHODS
DATA EXTRACTION STRATEGY: Data were extracted into an Access database by one reviewer and checked by a second. Any disagreements were resolved through discussion.
METHODS
QUALITY ASSESSMENT STRATEGY: Two reviewers, using specified criteria, independently assessed the quality of the clinical effectiveness studies and the economic evaluations. Any disagreements were resolved through discussion.
METHODS
ANALYSIS STRATEGY: Due to the limited number of studies included in the review and the fact that they compared topotecan with different comparators, the out-come data could not be pooled statistically. Clinical effectiveness data are discussed separately under the different outcome subheadings. For time-to-event data, hazard ratios with 95% confidence intervals are presented where available, and for the remaining outcomes, relative risks are reported or calculated where sufficient data were available. Relative risk data are also presented in the form of Forest plots without pooled estimates. Economic data are presented in the form of a summary and critique of the evidence, and a grading (A-I) assigned to each study indicating the direction and magnitude of the cost-effectiveness data.
INCLUDED STUDIES
A total of 568 titles/abstracts were identified and screened for relevance. Full copies of 72 papers were assessed and seven published manuscripts reporting details of two studies of clinical effectiveness and one economic evaluation were included. Further details of the two clinical effectiveness studies and two new economic evaluations were identified from confidential company submissions. Overall, two international multicentre RCTs of effectiveness comparing topotecan with paclitaxel (trial 039) and topotecan with caelyx (trial 30-49) were included in the review. The three economic evaluations included in the review comprised one cost-minimisation analysis (CMA) comparing topotecan with caelyx, one cost-consequences analysis (CCA) comparing topotecan with paclitaxel, etoposide and altretamine and one cost-effectiveness analysis (CEA) comparing topotecan with paclitaxel.
RESULTS
QUALITY OF CLINICAL EFFECTIVENESS DATA: Both clinical effectiveness studies (trial 30-49 and 039) were of reasonable quality, although it was unclear whether either performed valid intention-to-treat analyses. In addition, trial 30-49 failed to state whether the outcome assessors were blinded to treatment allocation. RESULTS --QUALITY OF ECONOMIC EVALUATIONS: The CCA (comparing topotecan with three comparators) was of poor quality and of little relevance to the UK NHS. The CMA and CEA were of reasonable quality overall and relevant to the UK NHS. However, both, in particular the CEA, suffered from methodological problems, and thus their findings should be interpreted with caution.
RESULTS
ASSESSMENT OF CLINICAL EFFECTIVENESS: The assessment of clinical effectiveness was based on limited data. Only two trials with a total of 709 participants were identified. In general, with a few minor exceptions, there were no statistically significant differences between topotecan and paclitaxel, or topotecan and caelyx in survival, response rate, median time to response, median duration of response and quality of life. Significant differences that were reported were mainly identified in subgroup analyses (Pt-sensitive disease and disease without ascites) of questionable validity and their relevance to a general advanced ovarian cancer patient population undergoing second-line chemotherapy is unclear. However, statistically significant differences were observed in the incidence of adverse effects. Topotecan was associated with increased incidences of haematological toxicities (including neutropenia, leukopenia, anaemia and thrombocytopenia), alopecia, nausea and vomiting. Caelyx-treated patients suffered from significantly increased incidences of Palmar-Plantar erythrodysesthesia, stomatitis, mucous membrane disorders and skin rashes. Paclitaxel was associated with significant increases in alopecia, arthralgia, myalgia, neuropathy, paraesthesiae, skeletal pain and flushing.
RESULTS
ASSESSMENT OF COST-EFFECTIVENESS: The assessment of cost-effectiveness was also based on limited data, with three evaluations identified, one of which was not relevant. The two remaining studies, comparing topotecan with paclitaxel (CEA) and topotecan with caelyx (CMA), both used effectiveness data from multicentre RCTs and based their costs on 1999/2000 UK sources. The evaluations were conducted from a UK NHS perspective and findings presented in GB pounds/Euros. Topotecan for the second-line treatment of advanced ovarian cancer was shown to be more cost-effective than paclitaxel (32,513 GB pounds versus 46,186 GB pounds per person in terms of any response (complete or partial), incremental cost-effectiveness = 3065 GB pounds) in all respects except cost per time without toxicity or symptoms, but less cost-effective than caelyx (14,023 GB pounds versus 9979 GB pounds per person regardless of whether the patient responded). However, direct comparisons of the cost findings between the two studies is difficult because they used different designs, different time horizons for the cost analyses and the findings were presented as costs per person for only patients who responded in one study (topotecan versus paclitaxel) and costs per person regardless of whether they responded in the other study (topotecan versus caelyx).
CONCLUSIONS
This review indicates that there is little evidence in the form of RCTs on which to base an assessment of the effectiveness of topotecan as second-line therapy for advanced ovarian cancer. The evidence suggests there were no statistically significant differences overall between topotecan and paclitaxel, or topotecan and caelyx in clinical outcomes. However, statistically significant differences were observed in the incidence of adverse effects. The clinical significance of the findings is not discussed. Overall, the effects of topotecan could at best be described as modest, but the alternative agents offer no real advantages except fewer side-effects and possibly improved cost-effectiveness. Both of the clinical effectiveness studies on which this evidence is based had methodological flaws, the most serious being the lack of a blinded assessor in the topotecan versus caelyx trial, which is important for unbiased assessment of response outcomes. The economic evaluations also suffered from a number of potential problems.
CONCLUSIONS
RECOMMENDATIONS FOR RESEARCH: Further good quality RCTs and CEAs are required comparing topotecan with other licensed and potentially useful (soon to be licensed) second-line treatments for ovarian cancer. At present, it is difficult to make any decisions about topotecan and other drugs for second-line therapy without good quality direct comparisons. In view of the ongoing studies identified, an update of the current review should be considered in approximately 18 months (Summer 2002) or possibly sooner if the recently commissioned National Institute for Clinical Excellence review of caelyx for ovarian cancer identifies additional data relevant to topotecan.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Female; Humans; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis; Technology Assessment, Biomedical; Topotecan
PubMed: 11701100
DOI: 10.3310/hta5280