Antiemetic research: future directions

Abstract

Purpose and methods 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. Results and conclusions 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.

Incidence and management of chemotherapy-induced nausea and vomiting in women with breast cancer

“…However, such emetogenic risk does not include nausea. (5) The potential presented by the most commonly used drugs in breast cancer treatment protocols can be classifi ed as: high, with a risk of vomiting of 90% (cyclophosphamide dosage over 1500mg/m 2 and cisplatine); moderate, with a 30% to 90% risk (cyclophosphamide dosage under 1500mg/m 2 , epirubicin and doxorubicin); low, with a 1% to 30% risk (5-fl uorouracil, paclitaxel, docetaxel, methotrexate, doxorubicin lipossomal, gemcitabina and trastuzumab); and minimal, with a risk of 10% or lower (vinorelbine). (6)(7) The emetogenic risk of each cytotoxic agent for inducing nausea and vomiting determines what drug or combination of antiemetic drugs must be used.…”

Aprepitant and Granisetron for the Prophylaxis of Radiotherapy-Induced Nausea and Vomiting after Moderately Emetogenic Radiotherapy for Bone Metastases: A Prospective Pilot Study

“…Patients within the 8 Gy arm were particularly well protected during the acute phase; no symptom or rescue antiemetic events were reported. That observation is notable for a number of reasons: Historically, nausea has been considered more difficult to control than vomiting 24 . Compared with conventional radiation doses of 1.8-2.0 Gy, high single doses such as 8 Gy are believed to increase the risk of rinv.…”

Nausea and vomiting induced by gastrointestinal radiation therapy

“…As such, decades of research into antiemetics has been driven largely by efforts to reduce the incidence of vomiting rather than nausea. Unfortunately, control rates for nausea have not improved in step with those for vomiting, and experts agree that a new generation of clinical trials are required that will use nausea as a primary endpoint [35]. Measuring the impact of RINV on quality of life should also be a goal of these new trials.…”