Medline ® Abstracts for References 46-49,102
of 'Prevention and treatment of chemotherapy-induced nausea and vomiting in adults'
Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy.
Hesketh PJ, Schnadig ID, Schwartzberg LS, Modiano MR, Jordan K, Arora S, Powers D, Aapro M
Cancer. 2016 Aug;122(15):2418-25. Epub 2016 May 13.
BACKGROUND: Rolapitant, a novel neurokinin-1 receptor antagonist, provided effective protection against chemotherapy-induced nausea and vomiting (CINV) in a randomized, double-blind phase 3 trial of patients receiving moderately emetogenic chemotherapy or an anthracycline and cyclophosphamide regimen. The current analysis explored the efficacy and safety of rolapitant in preventing CINV in a subgroup of patients receiving carboplatin.
METHODS: Patients were randomized 1:1 to receive oral rolapitant (180 mg) or a placebo 1 to 2 hours before chemotherapy administration; all patients received oral granisetron (2 mg) on days 1 to 3 and oral dexamethasone (20 mg) on day 1. A post hoc analysis examined the subgroup of patients receiving carboplatin in cycle 1. The efficacy endpoints were as follows: complete response (CR), no emesis, no nausea, no significant nausea, complete protection, time to first emesis or use of rescue medication, and no impact on daily life.
RESULTS: In the subgroup administered carboplatin-based chemotherapy (n = 401), a significantly higher proportion of patients in the rolapitant group versus the control group achieved a CR in the overall phase (0-120 hours; 80.2% vs 64.6%; P<.001) and in the delayed phase (>24-120 hours; 82.3% vs 65.6%; P<.001) after chemotherapy administration. Superior responses were also observed by the measures of no emesis, no nausea, and complete protection in the overall and delayed phases and by the time to first emesis or use of rescue medication. The incidence of treatment-emergent adverse events was similar for the rolapitant and control groups.
CONCLUSIONS: Rolapitant provided superior CINV protection to patients receiving carboplatin-based chemotherapy in comparison with the control. These results support rolapitant use as part of the antiemetic regimen in carboplatin-treated patients. Cancer 2016;122:2418-2425.©2016 American Cancer Society.
Department of Hematology and Oncology, Lahey Hospital&Medical Center, Burlington, Massachusetts.
A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy.
Tanioka M, Kitao A, Matsumoto K, Shibata N, Yamaguchi S, Fujiwara K, Minami H, Katakami N, Morita S, Negoro S
Br J Cancer. 2013 Aug;109(4):859-65. Epub 2013 Jul 16.
BACKGROUND: We evaluated the efficacy of aprepitant plus granisetron and an increased dose of dexamethasone in selected patients undergoing moderately emetogenic chemotherapy (MEC).
METHODS: Nondrinking women<70 years undergoing MEC were randomly assigned to aprepitant (day 1, 125 mg; days 2 and 3, 80 mg) or placebo. Dexamethasone on days 1-3 was 12, 4, and 4 mg with aprepitant and 20, 8, and 8 mg with placebo. The primary end point was complete response (CR; no emesis or rescue therapy) during 120 h of the first cycle. Logistic regression analysis was performed to identify predictors of overall CR.
RESULTS: Of the 94 patients enrolled, 91 were assessable. Most received carboplatin-based chemotherapy. In the aprepitant (n=45) and placebo (n=46) groups, the overall, acute (day 1), and delayed (days 2-5) CR rates were 62% and 52%, 98% and 96%, and 62% and 52%, respectively. Although not statistically significant, the overall CR rate was 10% higher in the aprepitant group. Both regimens were well tolerated. On multivariate analysis, advanced ovarian cancer (OR, 0.26 (0.10-0.72)) was independently associated with a lower CR.
CONCLUSION: Even with an increased dose of dexamethasone, aprepitant seemed more effective than placebo in these selected patients undergoing MEC; however, delayed phase management remains a significant problem.
Medical Oncology, Hyogo Cancer Center, Akashi, Japan. email@example.com
Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin.
Yahata H, Kobayashi H, Sonoda K, Shimokawa M, Ohgami T, Saito T, Ogawa S, Sakai K, Ichinoe A, Ueoka Y, Hasuo Y, Nishida M, Masuda S, Kato K
Int J Clin Oncol. 2016 Jun;21(3):491-7. Epub 2015 Dec 10.
BACKGROUND: Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy.
METHODS: We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with "no vomiting", "no significant nausea", and complete response, respectively.
RESULTS: Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of "no vomiting" patients (78.2 vs. 54.8 %; P < 0.0001), "no significant nausea" patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group.
CONCLUSION: The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.
Department of Obstetrics and Gynecology, Kyushu University Hospital, Fukuoka, Japan.
Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy.
Ito Y, Karayama M, Inui N, Kuroishi S, Nakano H, Nakamura Y, Yokomura K, Toyoshima M, Shirai T, Masuda M, Yamada T, Yasuda K, Hayakawa H, Suda T, Chida K
Lung Cancer. 2014 Jun;84(3):259-64. Epub 2014 Mar 27.
OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy.
METHODS: Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT(3) receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy.
RESULTS: A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2-88.1%) and 67.2% (95% CI, 55.3-77.2%; odds ratio (OR), 0.50; 95% CI, 0.22-1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08-0.70; p<0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07-0.65; p<0.01).
CONCLUSION: Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT(3) receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications.
Geling O, Eichler HG
J Clin Oncol. 2005;23(6):1289.
PURPOSE: 5-Hydroxytryptamine-3 receptor antagonists (5-HT(3) antagonists) are effective for preventing acute chemotherapy-induced emesis but the benefits of continuing administration of these agents beyond 24 hours after chemotherapy (delayed emesis) remain unclear. The purpose of this study was to provide estimates of clinical efficacy and drug acquisition cost associated with administering 5-HT(3) antagonists beyond 24 hours, as monotherapy or as added to dexamethasone.
METHODS: This analysis is based on the Cancer Care Ontario Practice Guidelines Initiative meta-analysis of the efficacy of 5-HT(3) antagonists. Results from the clinical trials covered in that meta-analysis were reanalyzed to provide estimates of absolute risk reductions (ARR) and numbers needed to treat (NNT) for 5-HT(3) antagonists, as monotherapy or as adjunct treatment. Numbers of 5-HT(3) antagonist unit doses per successfully treated patient were also calculated.
RESULTS: Five studies (comprising 1,716 assessable patients) compared a 5-HT(3) antagonist with placebo; five studies (2,240 patients) compared a combination of a 5-HT(3) antagonist and dexamethasone with dexamethasone monotherapy. ARR for monotherapy was only 8.2% (95% CI, 3.0% to 13.4%). On average, 74 5-HT(3) antagonist doses must be administered to 12 patients (NNT, 12.2; 95% CI, 7.5 to 33.4) not receiving dexamethasone to protect one patient from delayed emesis. In those patients receiving dexamethasone as standard antiemetic treatment in the delayed phase, the addition of a 5-HT(3) antagonist did not significantly improve control of delayed emesis as compared with dexamethasone monotherapy (ARR, 2.6%; 95% CI, -0.6% to 5.8%).
CONCLUSION: Neither clinical evidence nor considerations of cost effectiveness justify using 5-HT(3) antagonists beyond 24 hours after chemotherapy for prevention of delayed emesis.
Department of Public Health Sciences and Epidemiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, USA.