Curr. Oncol., Volume 14, Issue 5 (October 2007) – 9 articles

Anemia is a common finding in cancer patients, most often as a result of chemotherapy. Management of anemia requires a comprehensive approach of appropriate diagnosis, exclusion of reversible causes, use of erythropoiesis-stimulating agents (esas), and iron supplementation. Recently, consensus guidelines on the management of chemotherapy-induced anemia were published in Europe and the United States. The present review is intended to be a practical guide for Canadian physicians, based on published guidelines, but specifically tailored to the Canadian environment. Recommendations for the use of esas are presented, including initiation, target hemoglobin, dosing and adjustments, monitoring, and re-initiation. Issues of safety are also addressed, including thromboembolic risk, impact on survival, and tumour progression. The importance of iron metabolism and the use of iron supplementation (both oral and parenteral) is discussed. Full article

Question: What is the optimal chemotherapy treatment for women with recurrent ovarian cancer who have previously received platinum-based chemotherapy? Perspectives: Currently, standard primary therapy for advanced disease involves a combination of maximal cytoreductive surgery and chemotherapy with carboplatin plus paclitaxel or with carboplatin alone. Despite initial high response rates, a large proportion of patients relapse, resulting in a therapeutic challenge. Because these patients are not curable, the goal of therapy becomes improvement in both quality and length of life. The search has therefore been to find active agents for women with recurrent disease following platinum-based chemotherapy. Outcomes: Outcomes of interest included any combination of tumour response rate, progression-free survival, overall survival, adverse events, and quality of life. Methodology: The medline, embase, and Cochrane Library databases were systematically searched for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. The systematic review and recommendations were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (dsg). The practice guideline was externally reviewed by a sample of practitioners from Ontario, Canada. Results: Thirteen randomized trials compared various chemotherapy regimens for patients with recurrent ovarian cancer. In five of the thirteen trials in which 100% of patients were considered sensitive to platinum-containing chemotherapy, further platinum-based combination chemotherapy significantly improved response rates (two trials), progression-free survival (four trials), and overall survival (three trials) when compared with single-agent chemotherapy involving carboplatin or paclitaxel. Only two of these randomized trials compared the same chemotherapy regimens: carboplatin alone versus the combination of carboplatin and paclitaxel. Both trials were consistent in reporting improved survival outcomes with the combination of carboplatin and paclitaxel. In one trial, the combination of carboplatin and gemcitabine resulted in significantly higher response rates and improved progression-free survival when compared with carboplatin alone. Median survival with carboplatin alone ranged from 17 months to 24 months in four trials. In eight of the thirteen trials in which 35%–100% of patients had platinum-refractory or -resistant disease, one trial reported a statistically significant 2-month improvement in overall survival with liposomal doxorubicin as compared with topotecan (15 months vs. 13 months, p = 0.038; hazard ratio: 1.23; 95% confidence interval: 1.01 to 1.50). In that trial, because of the limited clinical benefit and the unusual finding that a survival difference emerged only after a year of treatment with no corresponding improvement in the rate of response or of progression-free survival, the authors concluded that further confirmation by results from randomized trials were needed to establish the superiority of one agent over another in their trial. In one trial, topotecan was superior to treosulphan in patient progression-free survival by a span of approximately 2 months (5.4 months vs. 3.0 months, p < 0.001). Toxicity was reported in all of the randomized trials, and although data on adverse events varied by treatment regimen, the observed adverse events correlated with known toxicity profiles. As expected, combination chemotherapy was associated with higher rates of adverse events. Practice Guideline: Target Population This clinical recommendation applies to women with recurrent epithelial ovarian cancer who have previously received platinum-based chemotherapy. Of specific interest are women who have previously shown sensitivity to platinum therapy and those who previously were refractory or resistant to platinum-based chemotherapy. As a general categorization within what is actually a continuum, “platinum sensitivity” refers to disease recurrence 6 months or more after prior platinum-containing chemotherapy, and “platinum resistance” refers to a response to platinum-based chemotherapy followed by relapse less than 6 months after chemotherapy is stopped. “Platinum-refractory disease” refers to a lack of response or to progression while on platinum-based chemotherapy. Recommendations Although the body of evidence that informs the clinical recommendations is based on randomized trial data, those data are incomplete. Based on the available data and expert consensus opinion, the Gynecology Cancer dsg makes these recommendations: Systemic therapy for recurrent ovarian cancer is not curative. It is therefore recognized that each patient must be individually assessed to determine optimal therapy in terms of recurrence, sensitivity to platinum, toxicity, ease of administration, and patient preference. All suitable patients should be offered the opportunity to participate in randomized trials, if available. In the absence of contraindications, combination platinum-based chemotherapy should be considered for patients with prior sensitivity to platinum-containing chemotherapy. As compared with carboplatin alone, the combination of carboplatin and paclitaxel significantly improved both progression-free and overall survival. If combination platinum-based chemotherapy is not indicated, then a single platinum agent should be considered. Carboplatin has demonstrated efficacy across trials and has a manageable toxicity profile. If a single platinum agent is not being considered, then monotherapy with paclitaxel, topotecan, or pegylated liposomal doxorubicin are seen as reasonable treatment options. Some patients may be repeatedly sensitive to treatment and may benefit from multiple lines of chemotherapy. For patients with platinum-refractory or platinum-resistant disease, the goals of treatment should be to improve quality of life by extending the symptom-free interval, by reducing symptom intensity, and by increasing progression-free interval, and, if possible, to prolong life. With non-platinum agents, monotherapy should be considered because no advantage appears to accrue to the use of non-platinum-containing combination chemotherapy in this group of patients. Single-agent paclitaxel, topotecan, or pegylated liposomal doxorubicin have demonstrated activity in this patient population and are reasonable treatment options. No evidence either supports or refutes the use of more than one line of chemotherapy in patients with platinum-refractory or platinum-resistant recurrence. Many treatment options have shown modest response rates, but their benefits over best supportive care have not been studied in clinical trials. Full article

Question: What is the safety and efficacy of interstitial chemotherapy with carmustine-loaded polymers (Gliadel wafers: MGI Pharma, Bloomington, MN, U.S.A.) in the treatment of newly diagnosed or recurrent malignant glioma (that is, glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligoastrocytoma, and anaplastic oligodendroglioma)? Perspectives: Malignant glioma is the most common type of primary brain tumour in adults. In general, efficacy of systemic therapy in this patient population has been disappointing, and novel treatment approaches are needed. Because several randomized controlled trials (rcts) investigating the safety and efficacy of Gliadel are available, the Neuro-oncology Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care decided that a systematic review of the evidence was necessary. Outcomes: The outcomes of interest for this review were overall survival, adverse events, and quality of life. Methodology: Systematic searches of the medline, embase, and Cochrane Library databases were conducted for relevant evidence. Fully-published reports of rcts comparing treatment with Gliadel wafers to placebo or alternative treatment were selected for inclusion. Prospective cohort studies were also included. Results: Two rcts that compared Gliadel to placebo in patients with newly diagnosed malignant glioma were obtained. Both rcts reported a significant survival benefit for patients who received Gliadel as compared with patients in the control group. One rct and one prospective cohort study were obtained that examined the role of Gliadel in patients with recurrent malignant glioma. The rct demonstrated a significant survival benefit for Gliadel only after adjustment for prognostic factors, and the prospective cohort study reported no survival benefit for Gliadel as compared with a historical control group. All three rcts reported similar rates of adverse events in the treatment and control groups. The most frequently reported adverse events were convulsions, confusion, brain edema, infection, hemiparesis, aphasia, and visual field defects. Conclusions: Gliadel is an option for selected patients with newly diagnosed malignant glioma where a near gross total resection is possible. No evidence is available comparing Gliadel with systemic therapy, and a decision to combine Gliadel with systemic therapy should be made for patients individually. The patient population that would benefit from Gliadel (age, histology, and performance status) is unclear; further investigation is needed. Gliadel is also an option for patients with surgically resectable recurrent malignant glioma. Full article

Question: What is the efficacy of pharmacologic and non-pharmacologic treatments for major depression and other depressive disorders in cancer populations? Perspectives: Depression occurs at an increased rate in medically ill populations, including patients with cancer. In the general population, depression has been shown to be responsive to structured forms of psychotherapy and to pharmacologic interventions. The Supportive Care Guidelines Group conducted a systematic review of the evidence for the effectiveness of those therapies in patients with depression and cancer and developed the present clinical practice guideline based on that review and on expert consensus. Outcomes: Outcomes of interest included symptomatic response to treatment, discontinuation rate of treatment, adverse effects, and quality of life. Methodology: Clinical recommendations were developed by the Supportive Care Guidelines Group based on a systematic review of the published literature through June 2005, feedback obtained from Ontario health care providers on the draft recommendations, the Report Approval Panel (rap) of Cancer Care Ontario’s Program in Evidence-Based Care, and expert consensus. Results: The systematic review of the literature included eleven trials (seven of pharmacologic agents and four of non-pharmacologic interventions). Feedback received from 44 responding health care providers and the rap on the draft recommendations was addressed and documented in the guideline. Among providers, 82% agreed with the draft recommendations as stated, 68% agreed that the report should be approved as a practice guideline, and 73% indicated that they would be likely to use the guideline in their own practice. Practice Guideline: These recommendations apply to adult cancer patients with a diagnosis of major depression or other non-bipolar depressive disorders. They do not address the treatment of non-syndromal depressive symptoms, for which specific antidepressant treatment is not usually indicated. The guideline is intended both for oncology health professionals and for mental health professionals engaged in the treatment of cancer patients. Expert consensus was central to the development of the guideline recommendations because of limited evidence in cancer patients. Recommendations: Treatment of pain and other reversible physical symptoms should be instituted before or with initiation of specific antidepressant treatment. Antidepressant medications should be considered for the treatment of moderate-to-severe major depression in cancer patients. Current evidence does not support the relative superiority of one pharmacologic treatment over another, nor the superiority of pharmacologic treatment over psychosocial interventions. The choice of an antidepressant should be informed by individual medication and patient factors: the side effect profiles of the medication, tolerability of treatment (including the potential for interaction with other current medications), response to prior treatment, and patient preference. Cancer patients diagnosed with major depression may benefit from a combined modality approach that includes both psychosocial and pharmacologic interventions. Psychosocial treatment approaches that may be of value include those that provide information and support and those that address any combination of emotional, cognitive, and behavioural factors. Qualifying Statements: Referral to a mental health specialist is appropriate when the diagnosis of depression is unclear, when the syndrome is severe, when patients do not respond to treatment, or when other complicating factors that may affect the choice of treatment are present. Although care has been taken in the preparation of the information contained in this guideline, any person seeking to apply or to consult the guideline is expected to use independent medical judgment in the context of individual clinical circumstances or to seek out the supervision of a qualified clinician. Full article

Cancer patients often experience multiple symptoms, and those symptoms can independently predict changes in patient function, treatment failures, and post-therapeutic outcomes. Symptom clusters are defined as two or more concurrent symptoms that are related and may or may not have a common cause. The purpose of the present study was to review, in cancer patients, common symptom clusters and their predictors. Using medline, embase, Cochrane Central, and cinahl, we conducted a literature search on symptom clusters in cancer patients. Studies that investigated predetermined clusters were not included. We identified seven individual studies and one group of five studies validating the M.D. Anderson Symptom Inventory. These studies had been published between 1997 and 2006. Two of the seven individual studies and the group of five studies that had validated the M.D. Anderson Symptom Inventory included patients with any cancer type; three studies included breast cancer patients only; and two studies included lung cancer patients only. A gastrointestinal cluster consisting of nausea and vomiting was the single cluster common to two of the studies. The severity of this cluster increased when patients were treated with chemotherapy. No common clusters were found in the lung and breast cancer patient populations. However, breast cancer patients experienced more symptom cluster involvement while undergoing chemotherapy. We noted methodology disparities among the papers with regard to assessment tools used, statistical analyses, and populations. Research on symptom clusters is still in an early stage. Multiple symptoms clearly affect prognosis, quality of life, and functional status. The study of symptom clusters is important for its implications regarding patient management, and a consensus on appropriate research methodology is vital. Full article

We used decision analysis techniques with Markov cohort modeling to examine the role of cancer antigen 125 (CA-125) in follow-up surveillance strategies among patients with advanced ovarian cancer. Utilities were derived from a societal perspective. Using quality-adjusted life years (QALYs) as the outcome variable, the value of CA-125 monitoring for asymptomatic women with ovarian cancer was found to be reduced as compared with a strategy that includes CA-125 testing. Decisions to include CA-125 in surveillance strategies for ovarian cancer patients should be made after discussion with full disclosure of the preference-sensitive nature of CA-125. The model demonstrates that preferences and perspective can influence decisions in cancer care. Full article

Developments in radiotherapy during the past 10–15 years, which have been driven largely by technological advances, have been nothing short of remarkable. Significant advances in tumour imaging, in radiotherapy treatment planning, and in dose delivery techniques have all contributed to improved treatment outcomes and have, in some situations, led to important changes in overall therapeutic approach [...] Full article