Avoidable Acute Care Use Associated with Nausea and Vomiting Among Patients Receiving Highly Emetogenic Chemotherapy or Oxaliplatin

PurposeChemotherapy‐induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare''s oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC.Materials and MethodsWe retrospectively evaluated U.S. electronic health records (2012‐2018) using Medicare''s OP‐35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non‐HEC. Antiemetic guideline adherence was defined as use ofneurokinin‐1 (NKl) receptor antagonists Q5 (RAs) plus 5‐hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation.ResultsAmong 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76‐1.91, p < .0001) as often after HEC versus non‐HEC excluding oxaliplatin; CINV‐related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA.ConclusionsPatients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline‐directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC.Implications for PracticeAfter survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy‐induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin‐1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.     

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial

BackgroundOlanzapine is an inexpensive and durable agent for the treatment of chemotherapy‐induced nausea and vomiting and is also superior to neurokinin‐1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)‐induced nausea and vomiting in patients with thoracic malignancies.Materials and MethodsWe conducted a prospective, open‐label, single‐arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0–120 hours).ResultsBetween February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0–120 hours), acute (0–24 hours), and delayed phases (24–120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed.ConclusionProphylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three‐drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA‐based regimen. Clinical trial identification number: UMIN000031267.Implications for PracticeThe results of this phase II trial indicated that the prophylactic administration of low‐dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high‐dose carboplatin chemotherapy.     

Aprepitant and Fosaprepitant: A 10‐Year Review of Efficacy and Safety

Chemotherapy‐induced nausea and vomiting (CINV) is a common adverse event associated with anticancer treatment that can have a significant adverse impact on patient health‐related quality of life and that can potentially undermine the effectiveness of chemotherapy. Traditional regimens to prevent CINV generally involved a combination of a corticosteroid plus a 5‐hydroxytryptamine (5HT₃) receptor antagonist (RA). In the past 10 years, antiemetic treatment has greatly advanced with the availability of the neurokinin‐1 receptor antagonist (NK₁ RA) aprepitant and its prodrug fosaprepitant. NK₁ RAs have a different mechanism of action in CINV than corticosteroids and 5HT₃ RAs, thus their use can complement traditional antiemetic drugs and can enhance control of CINV. This review examined accumulated data regarding the safety and efficacy of aprepitant and fosaprepitant over the decade since the first regulatory approval. Data from key studies of aprepitant and fosaprepitant in the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy were explored, as were recommendations in currently available guidelines for their use. In addition, their use as antiemetic therapy in special patient populations was highlighted. Future perspectives on potential uses of aprepitant and fosaprepitant for indications other than CINV are presented.     

Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review

The prevention of chemotherapy-induced nausea and vomiting (CINV) has been revolutionized over the past 25 years. Guideline-based treatment means that vomiting can be prevented in the majority, but not in all patients. Therefore, antiemetic research continues with the goal of optimizing CINV control for all patients. This comprehensive review summarizes the research efforts in this field over the past few years. Emerging from this research are two new antiemetic agents, netupitant/palonosetron, the first antiemetic combination agent and rolapitant, a new NK₁RA. In addition, studies have evaluated the benefits of olanzapine and ginger, explored optimal combinations of agents for delayed CINV prevention, confirmed that dexamethasone-sparing regimens are effective, and demonstrated the value of NK₁RAs in high-dose chemotherapy settings as well as with certain moderately emetogenic chemotherapies such as carboplatin. Research has also validated the correlation between antiemetic guideline adherence and improved CINV control. Finally, regulatory authorities have utilized extreme caution in retiring some 5-HT₃RAs or decreasing their maximum dose.     

Cervical Cancer in Sub-Saharan Africa: A Multinational Population-Based Cohort Study of Care and Guideline Adherence

BackgroundCervical cancer (CC) is the most common female cancer in many countries of sub‐Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS).MethodsOur observational study covered nine population‐based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44–125 patients diagnosed from 2010 to 2016 were selected in each. Cancer‐directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (U.S.) Guidelines.ResultsOf 632 patients, 15.8% received CDT with curative potential: 5.2% guideline‐adherent, 2.4% with minor deviations, and 8.2% with major deviations. CDT was not documented or was without curative potential in 22%; 15.7% were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Adherence was not assessed in 46.9% (no stage or follow‐up documented, 11.9%, or records not traced, 35.1%). The largest share of guideline‐adherent CDT was observed in Nairobi (49%) and the smallest in Maputo (4%). In patients with FIGO stage I–III disease (n = 190), minor and major guideline deviations were associated with impaired OS (hazard rate ratio [HRR], 1.73; 95% confidence interval [CI], 0.36–8.37; HRR, 1.97; CI, 0.59–6.56, respectively). CDT without curative potential (HRR, 3.88; CI, 1.19–12.71) and no CDT (HRR, 9.43; CI, 3.03–29.33) showed substantially worse survival.ConclusionWe found that only one in six patients with cervical cancer in SSA received CDT with curative potential. At least one‐fifth and possibly up to two‐thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of many patients.Implications for PracticeDespite evidence‐based interventions including guideline‐adherent treatment for cervical cancer (CC), there is huge disparity in survival across the globe. This comprehensive multinational population‐based registry study aimed to assess the status quo of presentation, treatment guideline adherence, and survival in eight countries. Patients across sub‐Saharan Africa present in late stages, and treatment guideline adherence is remarkably low. Both factors were associated with unfavorable survival. This report warns about the inability of most women with cervical cancer in sub‐Saharan Africa to access timely and high‐quality diagnostic and treatment services, serving as guidance to institutions and policy makers. With regard to clinical practice, there might be cancer‐directed treatment options that, although not fully guideline adherent, have relevant survival benefit. Others should perhaps not be chosen even under resource‐constrained circumstances.     

The compliance with antiemetic guidelines of Turkish medical oncologists. A survey study of Turkish Oncology Group

PurposeWe aimed to investigate the compliance of Turkish Medical Oncologists to antiemetic guidelines for treatment of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving high (HEC), moderate (MEC), and low (LEC) emetogenic chemotherapy.MethodA covering electronic mail letter with an online questionnaire link was sent to e-mail and mobile application groups including all 599 members of the Turkish Society of Medical Oncology in January 2018. The online survey has consisted of twelve questions.ResultsQuestionnaire form was responded by 146 of Turkish Medical Oncologists. The most of the participants were following up more than one antiemetic guideline (53%). While compliance with the antiemetic guidelines was higher in acute CINV prophylaxis for HEC and MEC, it was significantly lower in the delayed CINV treatment of HEC and LEC. The highest and lowest compliance rate was found in the prophylaxis of acute and delayed CINV of HEC (92% and 15%, respectively). The incidence of noncompliance for delayed CINV in HEC was statistically significantly higher in those who worked for ≤ five years in an oncology department, under 39 years of age, and non-academicians (p = 0.004, p = 0.042, p = 0.005, respectively).ConclusionsNoncompliance with the antiemetic guidelines is continue to be a big problem in Turkish Medical Oncologists. The use of standardized antiemetic protocols in chemotherapy order forms or a computerized decision-support system is now seen as a better tool to enhance compliance with the guidelines.     

Clinical practice guidelines on antiemetics in oncology

The tolerability of chemotherapy has been significantly improved by the advent of effective drugs and protocols for the amelioration of chemotherapy-induced nausea and vomiting. Variables such as the timing of nausea and vomiting (acute, delayed or anticipatory) and the emetogenicity of the chemotherapy must be taken into account in developing guidelines for antiemetic prophylaxis and treatment. Although there are a number of 5-hydroxytryptamine antagonists available, the clinical differences between them are small. The use of drugs with a different mechanism of action, such as the recently introduced neurokinin-1 receptor antagonist aprepitant, may be a useful adjunct to 5-hydroxytryptamine-3 receptor antagonists or steroid prophylaxis. The addition of aprepitant to standard antiemetic regimens increases the proportion of complete responses to antiemetic therapy. For the use of highly emetogenic chemotherapy in oncology a combination of 5-hydroxytryptamine-3 receptor antagonist, dexamethasone and aprepitant is recommended in the acute phase, and dexamethasone plus aprepitant during the subsequent days (many patients do not have their symptoms controlled by 5-hydroxytryptamine-3 receptor antagonist and steroid alone). In either case, lorazepam can be added as required. For moderately emetogenic chemotherapy, a regimen of 5-hydroxytryptamine, dexamethasone and aprepitant is recommended in the acute phase, followed by aprepitant alone in the delayed phase. Alternatively, a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone can be used in the acute phase, followed by dexamethasone for prophylaxis in the delayed phase. For chemotherapy with a low emetogenicity, either dexamethasone, metoclopramide, prochlorperazine or triethyperazine alone is recommended. No prophylaxis is generally required during the delayed phase and indeed may not be necessary during the acute phase either.     

Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT₃) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT₃ receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT₃ receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.     

Prevention of chemotherapy- and radiotherapy-induced emesis: Results of the Perugia Consensus Conference

Background: The need to review and summarize the evidence concerning preventive treatment of cancer chemotherapy- and radiotherapy-induced emesis.Design: After a survey among experts the Antiemetic Subcommittee of the MASCC planned and held a Consensus Conference on antiemetic therapy. Recommendations were provided on the basis of scientific confidence and the level of consensus among the participating experts.Results and conclusions: A 5-HT₃ antagonist plus dexamethasone is the regimen of choice in the prevention of acute emesis induced by single high, and low and repeated doses of cisplatin, and of acute emesis induced by moderately-high emetogenic chemotherapy (i.e., cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination) in both adults and children.In the prevention of delayed emesis induced by cisplatin the most efficacious choice is a combination of dexamethasone with either metoclopramide or a 5-HT₃ antagonist, while in moderately-high emetogenic chemotherapy dexamethasone alone or a 5-HT₃ antagonist alone or their combination should be used. No evidence or consensus exists regarding antiemetic treatment for patients receiving low emetogenic chemotherapy, or about the optimal rescue treatment for patients failing antiemetic prophylaxis. The best treatment for anticipatory emesis is the best possible control of acute and delayed emesis.Although 5-HT₃ antagonists have some efficacy in the prevention of acute emesis induced by high-dose chemotherapy, more studies should be carried out to determine the best preventive treatment. For prevention of acute emesis induced by highly/moderately emetogenic radiotherapy (TBI, irradiation of the upper part of the abdomen or of the whole abdomen/radiotherapy of the thorax, pelvis and lower body half) a 5-HT₃ antagonist is the best choice.     

Radiation-induced emesis: a problem with many open questions

Radiation-induced emesis (RIE) is often considered to be less frequent and less severe than nausea/vomiting encountered in patients receiving chemotherapy, although the issue has only been addressed in a few studies. It is possible that radiation oncologists undervalue the clinical relevance of RIE. If untreated, sickness produces an adverse effect on the patient's quality of life and may cause interruption of the treatment with possible unfavorable effects on tumor control. A prospective observational trial on RIE has recently been published by the Italian Group for Antiemetic Research in Radiotherapy (IGARR). The study evidenced that the overall cumulative incidence of vomiting and nausea occurred in about 40% of patients undergoing radiotherapy, and that the irradiated site, radiation field size, and previous chemotherapy were significant risk factors. Patients submitted to abdominal radiotherapy were at major risk of vomiting and nausea (71%), followed by those treated on the thorax, brain, head and neck, and pelvis (49%, 40%, 40%%, and 39%, respectively). Few small randomized clinical trials have evaluated the efficacy of various antiemetic drugs in preventing RIE. Generally, patients who entered these trials were those submitted to total body irradiation, half body irradiation or upper abdomen irradiation because of the greater risk of developing nausea and/or vomiting. The few controlled trials published have shown that dopamine receptor antagonists were effective in only about 50% of patients, whereas 5-hydroxytryptamine antagonists were more effective. Clinical practice guidelines for the use of antiemetics have recently been published by MASCC (Multinational Association of Supportive Care in Cancer) and ASCO (American Society of Clinical Oncology). Unfortunately, their recommendations were quite different, when classifying radiation emetogenic risk categories and when giving indications for the use of antiemetic drugs. However, MASCC and ASCO recommendations both suggested a prophylaxis with a 5-hydroxytryptamine antagonist and a corticosteroid for patients submitted to high emetogenic radiotherapy. There is evidence about the effectiveness of oral dexamethasone alone in fractionated upper abdomen radiotherapy and the use of a rescue antiemetic treatment as a possible alternative to the prophylaxis. Many questions remain open, and other prospective controlled trials on RIE are needed to answer them. Considering that radiotherapy to the abdomen, pelvis and thorax presents the most frequent problems in radiation oncology clinical practice, future trials on RIE should deal with these irradiated sites. The IGARR is carrying out a double-blind randomized clinical trial comparing prophylactic ondansetron plus dexamethasone versus ondansetron and dexamethasone given as a rescue treatment in patients undergoing fractionated radiotherapy to the upper abdomen.     

Antiemetic efficacy of an oral suspension of granisetron plus dexamethasone and influence of quality of life on risk for nausea and vomiting

OBJECTIVES: To assess the antiemetic efficacy of an oral suspension of granisetron/dexamethasone in patients receiving chemotherapy and to determine whether quality-of-life parameters influence the risk for postchemotherapy nausea and vomiting (PCNV). PATIENTS AND METHODS: In an open monocentric study, an oral suspension containing 2 mg granisetron and 16 mg (4 mg for moderately emetogenic chemotherapy) dexamethasone was administered to 43 chemotherapy-naive patients before highly (n = 16) or moderately (n = 27) emetogenic chemotherapy and on the 3 subsequent days (2 for moderately emetogenic chemotherapy). Emetic episodes were recorded and quality of life was assessed prior to each cycle with a questionnaire based on EORTC QLQ-30. RESULTS: In the group undergoing highly (moderately) emetogenic chemotherapy, complete control of acute vomiting was achieved in 60-72.7% (92.6-95.0%), and complete control of delayed vomiting in 37.5-40.0% (75.0-92.2%), of patients within the first 3 (5) cycles. The following quality-of-life parameters were significantly associated with PCNV: tiredness (RR = 1.3, p < 0.05), pain (RR = 1.5), impairment of daily life by pain (RR = 1.7), sensation of abdominal pressure and fullness (RR = 2.5), impairment of social activities (RR = 2.9). CONCLUSIONS: Once-daily oral administration of a suspension of granisetron/dexamethasone is an active prophylaxis of nausea and vomiting and compares favorably with data reported on intravenous administration. Quality-of-life parameters assessed pre-treatment could help to identify patients at high risk for nausea and vomiting so that antiemetic therapy can be tailored to individual patient risk.     

A randomized phase III study evaluating the efficacy and safety of NEPA,a fixed-dose combination of netupitant and palonosetron,for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy

BackgroundAntiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK₁ receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT₃ RA, which targets dual antiemetic pathways.Patients and methodsThis multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline–cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25–120 h) phase in cycle 1.ResultsThe percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0–120 h) (74.3% versus 66.6%; P = 0.001) and acute (0–24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO.ConclusionsNEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.     

Clinical practice guidelines on antiemetics in oncology

The tolerability of chemotherapy has been significantly improved by the advent of effective drugs and protocols for the amelioration of chemotherapy-induced nausea and vomiting. Variables such as the timing of nausea and vomiting (acute, delayed or anticipatory) and the emetogenicity of the chemotherapy must be taken into account in developing guidelines for antiemetic prophylaxis and treatment. Although there are a number of 5-hydroxytryptamine antagonists available, the clinical differences between them are small. The use of drugs with a different mechanism of action, such as the recently introduced neurokinin-1 receptor antagonist aprepitant, may be a useful adjunct to 5-hydroxytryptamine-3 receptor antagonists or steroid prophylaxis. The addition of aprepitant to standard antiemetic regimens increases the proportion of complete responses to antiemetic therapy. For the use of highly emetogenic chemotherapy in oncology a combination of 5-hydroxytryptamine-3 receptor antagonist, dexamethasone and aprepitant is recommended in the acute phase, and dexamethasone plus aprepitant during the subsequent days (many patients do not have their symptoms controlled by 5-hydroxytryptamine-3 receptor antagonist and steroid alone). In either case, lorazepam can be added as required. For moderately emetogenic chemotherapy, a regimen of 5-hydroxytryptamine, dexamethasone and aprepitant is recommended in the acute phase, followed by aprepitant alone in the delayed phase. Alternatively, a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone can be used in the acute phase, followed by dexamethasone for prophylaxis in the delayed phase. For chemotherapy with a low emetogenicity, either dexamethasone, metoclopramide, prochlorperazine or triethyperazine alone is recommended. No prophylaxis is generally required during the delayed phase and indeed may not be necessary during the acute phase either.     

5HT3RA plus dexamethasone plus aprepitant for controlling delayed chemotherapy‐induced nausea and vomiting in colorectal cancer

Delayed chemotherapy‐induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L‐OHP)‐based chemotherapy. Whether neurokinin‐1 receptor antagonist addition to a first‐generation 5HT₃ antagonist (1st 5‐HT₃RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5‐HT₃RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L‐OHP–based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5‐HT₃RA+DEX+APR (APR) groups by propensity score–matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5‐HT₃RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L‐OHP–based chemotherapy should be treated with three antiemetics, including APR.     

Comparative efficacy and tolerability of antiemetic prophylaxis for adult highly emetogenic chemotherapy: A network meta‐analysis of 143 randomized controlled trials

Chemotherapy‐induced nausea and vomiting (CINV) is one of the commonest side‐effects among cancer patients. However, there is lacking of hierarchical evidences comparing different antiemetics against highly emetogenic chemotherapy. Therefore, we conducted a network meta‐analysis to investigate their comparative efficacy and tolerability. Randomized controlled trials that compared different antiemetic categories for adult highly emetogenic chemotherapy were included after searching PubMed, Web of Science, Embase and Cochrane Central. Acute‐phase no emesis and no nausea were identified as primary endpoints. We made pairwise and hierarchical calculations by random‐effects model. Effect sizes were presented by odds ratio and 95% confidential interval. Subgroup analysis was additionally performed. 143 randomized trials were included into pooled analysis, containing 22,776 patients and 18 antiemetic categories. 5‐HT₃ RA plus corticosteroid plus NK‐1 RA plus other (5CNO) displayed best protection against both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5‐HT₃ RA plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no‐naivety and anthracycline plus cyclophosphamide (AC)‐based studies. On the other hand, 5‐HT₃ RA plus dopamine RA plus other (5DO) may be best fit for delayed emesis (92.0%) and nausea (92.7%). Subgroups featuring no‐naivety and AC‐based trials preferred 5DO (91.9%) and 5CN (88.6%), respectively. In addition, dopamine RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except for AC‐based subgroup where corticosteroid plus dopamine RA plus other (CDO) preponderated (69.2%). 5CNO and 5DO should be considered as first‐line regimens against highly emetogenic chemotherapy induced acute and delayed CINV, respectively.     

Antiemetic properties of the 5HT3-receptor antagonist, gr38032f

GR38032F is a highly selective 5HT₃-receptor antagonist which inhibits vomiting induced by cisplatin, cyclophosphamide or X-radiation in the ferret. Since cisplatin selectively increased the levels of 5HT and 5HIAA in the intestinal mucosa, a possible site of the antiemetic action of GR38032F may be on 5HT₃-receptors on vagal afferents in the small intestine. The potent antiemetic action of GR38032F should be of clinical value in reducing the nausea and vomiting associated with radioterapy or chemotherapy of cancer.     

5‐HT3 antiemetic therapy for patients with breast cancer

Antiemetic treatment should be considered for breast cancer patients receiving moderately emetogenic chemotherapy. Although the extent of chemotherapyinduced emesis is largely dependent on the emetogenic potential of the specific agents employed, patient characteristics such as age and sex also contribute. Recent clinical studies show that treatment with the currently available 5HT₃ antagonists effectively reduces the incidence of chemotherapyinduced nausea and vomiting and improves quality of life in a substantial number of these patients.A Medline search from 1994 through February 1998 identified clinical trials that included previously untreated breast cancer patients using antiemetic therapy such as granisetron, ondansetron, dolasetron, and metoclopramide.The studies reviewed here indicate that the antiemetic efficacy of 5HT₃ antagonists is equivalent in previously untreated patients receiving moderately emetogenic chemotherapy for breast cancer, depending on the doses and schedules utilized. In particular, two comparative studies of granisetron and ondansetron with specific data for breast cancer patients showed that both agents eliminate nausea in approximately 50%, and vomiting in 60–70% of these patients, with the higher values observed when steroids were added to the 5HT₃ receptor antagonist regimen.Although the chemotherapy regimens employed for breast cancer are considered only moderately emetogenic, these regimens account for 60–90% of patients experiencing nausea and vomiting. The most recent clinical studies demonstrate that 5HT₃ antagonists can significantly reduce the incidence of nausea in breast cancer patients receiving moderately emetogenic chemotherapy and should be employed in this setting.     

Granisetron is equivalent to ondansetron for prophylaxis of chemotherapy-induced nausea and vomiting: results of a meta-analysis of randomized controlled trials

BACKGROUND: The introduction of serotonin antagonists as antiemetics for prophylaxis of chemotherapy-induced nausea and vomiting represented a major step toward better patient tolerance and adherence to this type of treatment. Several published trials compared different serotonin antagonists without demonstrating clear superiority of any one of them. Because most of these trials compared ondansetron with granisetron, the authors conducted a meta-analysis to determine if the current data available show any therapeutic difference between them. METHODS: MEDLINE and CANCERLIT databases were searched from 1990 to May 1999, and pertinent article references also were surveyed, without restriction to English language. The authors included all randomized controlled trials (RCTs) that had more than 25 patients per arm and compared ondansetron to granisetron for prophylaxis of acute (A) (< 24 hours) and delayed (D) (> 24 hours) nausea (N) and vomiting (V) induced by highly (H) or moderately (M) emetogenic chemotherapy. Only the first chemotherapy cycle was considered for studies that involved a crossover design. RESULTS: Fourteen studies with 6467 evaluable patients among the 21 studies retrieved were selected for this meta-analysis. In none of the eight scenarios studied (AHV, AHN, AMV, AMN, DHV, DHN, DMV, and DMN) could the authors detect any significant differences in the antiemetic efficacy of any of these medications. CONCLUSIONS: The authors conclude that both granisetron and ondansetron have similar antiemetic efficacy for prophylaxis of chemotherapy-induced nausea and vomiting. Because the number of comparative studies that addressed the delayed nausea and vomiting scenarios is low, further RCTs are still needed to confirm these results.     

Metoclopramide,Dexamethasone, or Palonosetron for Prevention of Delayed Chemotherapy‐Induced Nausea and Vomiting After Moderately Emetogenic Chemotherapy (MEDEA): A Randomized,Phase III,Noninferiority Trial

BackgroundFor the prevention of chemotherapy‐induced nausea and vomiting (CINV) during the delayed phase (24–120 hours) after moderately emetogenic chemotherapy (MEC), the use of 3‐day dexamethasone (DEX) is often recommended. This study compared the efficacy and safety of two DEX‐sparing regimens with 3‐day DEX, focusing on delayed nausea.Patients and MethodsThis open‐label, randomized, phase III study was designed to demonstrate noninferiority of two DEX‐sparing regimens: ondansetron + DEX on day 1 + metoclopramide on days 2–3 (MCP arm), and palonosetron + DEX on day 1 (PAL arm) versus ondansetron on day 1 + DEX on days 1–3 (DEX arm) in chemotherapy‐naïve patients receiving MEC. Primary efficacy endpoint was total control (TC; no emetic episodes, no use of rescue medication, no nausea) in the delayed phase. Noninferiority was defined as a lower 95% CI greater than the noninferiority margin set at −20%. Secondary endpoints included no vomiting, no rescue medication, no (significant) nausea, impact of CINV on quality of life, and antiemetics‐associated side effects.ResultsTreatment arms were comparable for 189 patients analyzed: predominantly male (55.7%), median age 65.0 years, colorectal cancer (85.7%), and oxaliplatin‐based chemotherapy (81.5%). MCP demonstrated noninferiority to DEX for delayed TC (MCP 56.1% vs. DEX 50.0%; 95% CI, −11.3%, 23.5%). PAL also demonstrated noninferiority to DEX (PAL 55.6% vs. DEX 50.0%; 95% CI, −12.0%, 23.2%). There were no statistically significant differences for all secondary endpoints between treatment arms.ConclusionThis study showed that DEX‐sparing regimens are noninferior to multiple‐day DEX in terms of delayed TC rate in patients undergoing MEC. ClinicalTrials.gov identifier. {"type":"clinical-trial","attrs":{"text":"NCT02135510","term_id":"NCT02135510"}}NCT02135510.Implications for PracticeChemotherapy‐induced nausea and vomiting (CINV) in the delayed phase (24–120 hours after chemotherapy) remains one of the most troublesome adverse effects associated with cancer treatment. In particular, delayed nausea is often poorly controlled. The role of dexamethasone (DEX) in the prevention of delayed nausea after moderately emetogenic chemotherapy (MEC) is controversial. This study is the first to include nausea assessment as a part of the primary study outcome to better gauge the effectiveness of CINV control and patients’ experience. Results show that a DEX‐sparing strategy does not result in any significant loss of overall antiemetic control: DEX‐sparing strategies incorporating palonosetron or multiple‐day metoclopramide are safe and at least as effective as standard treatment with a 3‐day DEX regimen with ondansetron in controlling delayed CINV—and nausea in particular—following MEC.     

Antiemetic effects of granisetron and dexamethasone combination therapy during cisplatin-containing chemotherapy for head and neck cancer: dexamethasone dosage verification trial

Background

Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for patients and is associated with a substantial deterioration in quality of life; appropriate use of antiemetic drugs is crucial in maintaining the quality of life in patients undergoing chemotherapy.

Methods

This randomized, crossover trial evaluated the antiemetic efficacy and safety of 8 mg per day (low-dose) and 16 mg per day (standard-dose) dexamethasone, in combination with the 5-HT₃ receptor antagonist granisetron, in 36 patients receiving cisplatin (CDDP)-containing chemotherapy for head and neck cancer. Following chemotherapy, the antinausea/vomiting inhibition rate for each dexamethasone dose was measured.

Results

During the 24-h period following administration of chemotherapy (acute phase), the antinausea/vomiting inhibition rates (no nausea and no episodes of vomiting) for 8 mg and 16 mg dexamethasone were comparably high (58.3% and 63.8%, respectively; P = 0.8092). Similar results were seen on days 2–5 following chemotherapy. Efficacy during the acute phase, based on the number of instances of vomiting and degree of nausea, was also comparably high for the two dexamethasone doses (overall efficacy rates were 94.4% and 88.8%, respectively, for 8 mg and 16 mg dexamethasone; P = 0.7637). Both doses maintained an 80% or higher response rate until day 3, and neither dose produced severe side effects.

Conclusion

The results suggest that granisetron and dexamethasone combination therapy is useful in controlling acute and delayed nausea and vomiting induced by CDDP-containing chemotherapy for head and neck cancer. Furthermore, 8 mg and 16 mg dexamethasone have equivalent antiemetic efficacy.