Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
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Support Care Cancer · Mar 2011
ReviewEvaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--state of the art.
Antiemetic drug development can follow the same logical path as antineoplastic drug development from appropriate preclinical models through Phase I, Phase II, and Phase III testing. However, due to the marked success of antiemetic therapy over the last 25 years, placebo antiemetic treatment against highly or moderately emetogenic chemotherapy is not acceptable. Promising antiemetic agents therefore rapidly reach Phase III testing, where they are substituted into or added to effective and accepted regimens. ⋯ Since oral chemotherapeutic agents are often administered in extended regimens, the distinction between acute and delayed emesis is less clear, and cumulative emesis must be considered. As control of vomiting has improved, attention has shifted to control of nausea, a related but distinct and equally important problem. Additional efforts will be necessary to understand mechanisms of nausea and to identify optimal remedies.
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This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference in April 2004. The following issues will be addressed: dose and schedule of antiemetics, different groups of antiemetics such as corticosteroids, serotonin(3) receptor antagonists, dopamine(2) receptor antagonists, and neurokinin(1) receptor antagonists. ⋯ Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004 version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone on days 2-3. In patients receiving a combination of an anthracycline plus cyclophosphamide, a combination of a serotonin(3) receptor antagonist plus dexamethasone, plus the neurokinin(1) receptor antagonist aprepitant on the day of chemotherapy, followed by aprepitant days 2-3, is recommended.
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Support Care Cancer · Mar 2011
Practice GuidelineAntiemetics in children receiving chemotherapy. MASCC/ESMO guideline update 2009.
Only a few studies have been carried out in children on the prevention of chemotherapy-induced nausea and vomiting (CINV). 5-HT(3) receptor antagonists have been shown to be more efficacious and less toxic than metoclopramide, phenothiazines and cannabinoids. Most dose studies are available for the 5-HT(3) receptor antagonists ondansetron and granisetron. The new 5-HT(3) receptor antagonist palonosetron was evaluated in one comparative study so far showing promising activity. ⋯ No studies have specifically evaluated antiemetic drugs in the prevention of chemotherapy-induced delayed and anticipatory emesis in children. The role of the NK1 receptor antagonists in children has to be further investigated, although one small study is published so far, showing promising activity in the prevention of CINV with aprepitant. The new proposed guideline from the Multinational Association of Supportive Care in Cancer and the European Society of Clinical Oncology summarises the updated data from the literature and takes into consideration the existing guidelines.
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Support Care Cancer · Mar 2011
Clinical TrialThe use of fentanyl buccal tablets as breakthrough medication in patients receiving chronic methadone therapy: an open label preliminary study.
Data on the treatment of breakthrough cancer pain (BTcP) in patients receiving methadone therapy are lacking. Whether methadone produces tolerance to other opioids, other opioids should be less effective when administered as a BTcP medication. ⋯ FBT was effective as breakthrough pain medication in patients receiving methadone for their background analgesia, confirming that this group of patients are not inevitably resistant to other opioids.
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As a part of reviewing the Multinational Association of Supportive Care in Cancer (MASCC) antiemetic guidelines in Perugia in 2009, an expert group identified directions for future antiemetic research. ⋯ In future trials, the prediction of nausea and vomiting may combine algorithms based on observed prognostic factors relating to the patient and the anticancer therapy, the identification of the genes that code for receptors, and pharmacogenetic studies of the metabolism of drugs. Design issues for future trials include standardising the emetic stimulus across studies and finding the minimum tolerated effective dose and schedule of an antiemetic. Also control of delayed emesis is not independent of the control of acute emesis. The full range of side effects and the impact on global quality of life scores should be part of the routine assessment of an antiemetic. With current high rates of control of acute vomiting, future trials will need to consider new primary endpoints such as nausea, a complex symptom, where improvement is needed. Economic endpoints should be incorporated to ascertain the cost benefit of antiemetic prophylaxis, taking into account the impact of nausea on work capacity. New antiemetic drugs may be targeted at different receptors, such as opioid, cannabinoid and peptide YY receptors. New research is needed into determining the extent of corticosteroid use. The emetic potential of a range of newer cytotoxics particularly when used in combinations and different scheduling, such as prolonged oral dosing of cytotoxics and use of targeted therapies, are all areas in need of research. More antiemetic studies are needed in niche areas such as in patients receiving high dose chemotherapy, radiation therapy or combined modality therapy. Further evidence of the efficacy of newer antiemetic agents is required in children.