aprepitant and Breast-Neoplasms

The neurokinin-1 (NK1) receptor antagonist aprepitant has become part of standard antiemetic therapy for high-dose cisplatin. Recent results indicate that chemotherapy for breast cancer that contains an anthracycline plus cyclophosphamide is more emetogenic than has been previously realised. One large randomised trial demonstrated that aprepitant substantially reduces the risk of vomiting or retching when added to a corticosteroid and a 5-hydroxytryptamine 3 (HT3) receptor antagonist. The adverse effects of standard antiemetics and chemotherapy do not appear to be increased by the addition of this novel antiemetic agent. Aprepitant should now also be considered to be part of prophylactic antiemetic therapy for women who receive chemotherapy that contains an anthracycline and cyclophosphamide. The role of NK1 receptor antagonists in preventing emesis due to other cytotoxic agents that are deemed to be moderately emetogenic is still unclear.

Topics: Adrenal Cortex Hormones; Anthracyclines; Antibiotics, Antineoplastic; Antiemetics; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cisplatin; Cyclophosphamide; Dopamine Antagonists; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine.. Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored.. 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment.. The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; China; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Middle Aged; Nausea; Olanzapine; Ondansetron; Vomiting

Background We examined the efficacy of mirtazapine in preventing delayed nausea and vomiting following highly emetogenic chemotherapy (HEC). Patients and methods Patients who had experienced delayed emesis and would be subsequently scheduled for at least three more cycles of the same chemotherapy were randomly assigned to either a mirtazapine (15 mg daily on days 2-4) or a control group. In addition, both groups received a standard triplet regimen comprising aprepitant, a 5-HT3 receptor antagonist, and dexamethasone (7.5 mg on days 2-4). The chemotherapy regimens were either an epirubicin plus cyclophosphamide regimen or cisplatin-containing regimens. The primary end point was a complete response (no emesis and no rescue treatment) to the delayed phase (25-120 h post-chemotherapy) during Cycle 1. The impact on quality of life (QOL) was assessed using the Functional Living Index-Emesis (FLIE) questionnaire. Results Of 95 enrolled patients, 46 were assigned to the mirtazapine group and 49 to the control group. The complete response rate in the delayed phase during Cycle 1 was significantly higher with mirtazapine than in the control group (78.3% versus 49.0%, P = 0.003). The main adverse effects of mirtazapine were mild to moderate somnolence and weight gain. Mean total FLIE scores were similar between the two arms. Conclusions This is the first randomized prospective study to show that adding mirtazapine has a substantial and statistically significant benefit with good tolerance in patients with breast cancer who have experienced delayed emesis following the same prior HEC. (Trial registration: ClinicalTrials.gov NCT02336750).

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cisplatin; Cyclophosphamide; Dexamethasone; Dopamine Antagonists; Epirubicin; Female; Humans; Middle Aged; Mirtazapine; Nausea; Quality of Life; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

To evaluate the addition of a fourth antiemetic intervention in patients at high risk for postoperative nausea and vomiting (PONV).. High-risk patients (Apfel score 3 or 4) scheduled for unilateral mastectomy were randomly allocated in one of two groups, oral aprepitant (oral aprepitant 80 mg, intravenous dexamethasone 8 mg, and palonosetron 0.075 mg) and oral placebo (oral placebo, intravenous dexamethasone 4 mg, and palonosetron 0.075 mg). Patients and caregivers were blinded to the group assignments. The primary efficacy endpoints included the incidence of nausea and vomiting, and the secondary endpoints included use of rescue antiemetics during a 48-hour postoperative period. ClinicalTrials.gov: NCT02431286.. One hundred patients were enrolled in this study and 91 were analyzed, 48 in group A and 43 in group P. No patient presented with nausea or vomiting in the first 2 hours after surgery. From the 2nd to the 6th hour, the incidence of PONV was 8.33% in group A and 9.30% in group P. In the first 24 hours, the incidence of PONV was 27.08% in the group A and 20.93% in group P. From the 24th to the 48th hour, the incidence of PONV was 8.33% in group A and 13.95% in group P. There were no statistically significant differences in PONV between groups.. The addition of aprepitant as a third antiemetic resulted in no significant reduction in the incidence of PONV in this population. However, the incidence of PONV was reduced in relation to the general population.

Topics: Aprepitant; Breast Neoplasms; Double-Blind Method; Humans; Mastectomy; Palonosetron; Postoperative Nausea and Vomiting

Dexamethasone, plus a 5-HT3 receptor antagonist and an NK-1 receptor antagonist are recommended for controlling the chemotherapy-induced nausea and vomiting (CINV) of highly emetogenic chemotherapy. Several days of dexamethasone are effective for CINV; however, dexamethasone also has side effects. The purpose of this trial was to investigate whether the use of a second-generation 5-HT3 receptor antagonist and an NK-1 receptor antagonist could allow a reduced dose of dexamethasone for breast cancer patients receiving highly emetogenic chemotherapy.. Eighty breast cancer patients who received an anthracycline-cyclophosphamide combination regimen were enrolled. The patients were randomized to arm A (dexamethasone days 1-3) and arm B (dexamethasone day 1). The primary endpoint was complete response (CR) (no emetic episodes and no rescue medication) during the overall phase (days 1-5). The secondary endpoints were the CR during the delayed phase (days 2-5), complete control (CC) (no emetic episodes, no rescue medication, and no more than mild nausea) during the overall phase, and the safety of this antiemetic therapy.. There were no significant differences in the rates of CR and CC between arm A and B as follows: CR overall phase--arm A: 82.9%, 90% confidence interval [CI] 71.3-90.5% vs arm B: 82.1%, 90% CI 70.0-90.0%; p = 1.00; CR delayed phase--arm A: 87.8%, 90% CI 77.0-93.9% vs arm B: 94.9%, 90% CI 85.6-98.3%; p = 0.43; CC overall phase--arm A: 48.8%, 90% CI 36.4-61.3% vs arm B: 61.5%, 90% CI 48.4-73.2%; p = 0.27. There were very few adverse events and no severe adverse events associated with this antiemetic therapy.. The results suggest that the antiemetic effect provided by dexamethasone administered for 3 days can be obtained by dexamethasone administered for 1 day.

Topics: Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Dexamethasone; Female; Humans; Isoquinolines; Japan; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Vomiting

The objective of this exploratory analysis was to determine if individual patient risk factors could be used to optimize chemotherapy-induced nausea and vomiting (CINV).. Through validated risk prediction models which quantify patient risk factors, 152 patients with early-stage breast cancer scheduled to received adjuvant anthracycline-based chemotherapy were categorized as being at low (level 0) or high-risk (level 1) for CINV. Prior to the first cycle of chemotherapy, low-risk patients received ondansetron and dexamethasone, while high-risk level 1 patients also received aprepitant. For subsequent cycles, patients who experienced CINV had their antiemetics changed in a stepwise manner to level 2 (extended-duration dexamethasone) or level 3 (extended-duration dexamethasone and low-dose olanzapine).. The study enrolled 152 patients who received 484 cycles of chemotherapy. Forty patient cycles were classified as low risk (level 0) compared to 201, 162 and 81 that were classified as high-risk levels 1, 2 and 3, respectively. Complete control of acute and delayed vomiting was comparable and was achieved in over 85 % of patients across all risk levels (p = 0.56 and p = 0.99). In contrast, complete control of acute and delayed nausea was reduced in risk levels 1 to 3 compared to level 0 (acute = 51.2, 58.0, 45.7 vs. 70.0 %; p = 0.013)-(delayed = 32.8, 45.7, 34.6 vs. 62.5 %; p < 0.001).. Despite the addition of aprepitant, extended-duration dexamethasone and olanzapine, patients at high risk for CINV due to personal risk factors failed to achieve good nausea control.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Dexamethasone; Female; Humans; Middle Aged; Morpholines; Nausea; Ondansetron; Outcome Assessment, Health Care; Practice Guidelines as Topic; Risk Factors; Vomiting

Docetaxel-cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy-induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients.. This prospective multicentre study enrolled 212 chemotherapy-naïve EBC patients receiving T-75 mg/m(2) and C-600 mg/m(2). Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT3) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2.. Among the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2-91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8-72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8-38.1, p = 0.0124) and 2 (18.3-42.9, p = 0.0059).. Guideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Docetaxel; Female; Humans; Middle Aged; Morpholines; Nausea; Neoplasm Staging; Prospective Studies; Quality of Life; Salvage Therapy; Secondary Prevention; Serotonin 5-HT3 Receptor Antagonists; Spain; Surveys and Questionnaires; Taxoids; Time Factors; Treatment Outcome; Vomiting

Chemotherapy regimens for breast cancer containing anthracycline and cyclophosphamide are classified as highly emetogenic. Aprepitant (A), palonosetron (P), granisetron (G), or dexamethasone (D) are recommended antiemetic drugs. However, it is uncertain which combination is most effective. We retrospectively examined the efficacy of these antiemetic drugs.. We reviewed the medical records of 454 patients with breast cancer treated in our facility with regimens containing anthracycline and cyclophosphamide between August 2009 and September 2010.. The number of patients treated with GD, AGD, and APD was 147, 150, and 157, respectively. Complete response (CR) in the acute (0-24 h) and delayed (24-120 h) phases was 68.7 and 76.2 %, respectively, for GD, 90.0 and 92.7 %, respectively, for AGD, and 89.8 and 90.4 %, respectively, for APD. Complete control (CC) in the acute and delayed phases for each regimen was 60.5 and 64.6 %, respectively, for GD, 62.7 and 88.7 %, respectively, for AGD, and 84.1 and 87.3 %, respectively, for APD. In the acute and delayed phases CR for AGD or APD was significantly superior to that for GD (P < 0.01). It worth noting that CC for APD in the acute phase was significantly superior to that for AGD (P < 0.01). In the delayed phase CC for AGD or APD was significantly superior to that for GD.. A combination of aprepitant, palonosetron, and dexamethasone is an antiemetic treatment of choice for patients treated with regimens containing anthracycline and cyclophosphamide.

Topics: Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Dexamethasone; Female; Granisetron; Humans; Isoquinolines; Middle Aged; Morpholines; Palonosetron; Quinuclidines; Retrospective Studies; Treatment Outcome; Vomiting

The aim of our study was to evaluate the efficacy and safety of a three-drug antiemetic prophylaxis in a single-center series treated with anthracyclines and cyclophosphamide-based regimen for BC. We collected data from 92 consecutive patients treated with routine antiemetic prophylaxis consisted of aprepitant (oral 125 mg, on day 1; oral 80 mg, on days 2 and 3), a 5-HT3 receptor antagonist (palonosetron iv 0.25 mg, on day 1), and dexamethasone (iv 12 mg, on day 1). Acute and delayed phases were defined as the first 24 h and days 2-5 after treatment, respectively. Therapy outcomes were defined as complete response (CR), in case of no vomiting, no rescue treatment; complete protection (CP), in case of no vomiting, no rescue treatment, no significant nausea; and total control (TC), in case of no vomiting, no rescue treatment, no nausea. Overall, 89.1 and 81.5% of patients showed CR in acute and delayed phase, respectively; 67.4 and 62% showed CP in acute and delayed phase, respectively; and 52.2 and 48.9% of patients showed TC in acute and delayed phase, respectively. 4.3% complained an episode of emesis during the first 24 h from treatment, while in delayed phase, only 2.2% of patients had vomiting. Our analysis confirmed that a three-drug prophylaxis is safe, effective, and consequently highly recommended in patients who undergo anthracyclines and cyclophosphamide-based regimens, though still not classified as highly emetogenic chemotherapy by all the international guidelines.

Topics: Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Dexamethasone; Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

A combination of aprepitant, a 5-HT3 receptor antagonist, and dexamethasone is recommended for the prophylaxis of acute or delayed emesis induced by chemotherapy containing anthracyclines plus cyclophosphamide in patients with breast cancer. The aim of this study was to verify whether dexamethasone is superior to aprepitant in preventing delayed emesis in patients receiving the same prophylaxis for acute emesis.. A randomized double-blind study comparing aprepitant versus dexamethasone was completed in chemotherapy-naive patients with breast cancer treated with anthracyclines plus cyclophosphamide. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg, dexamethasone 8 mg, and oral aprepitant 125 mg. On days 2 and 3, patients randomly received oral dexamethasone 4 mg twice per day or aprepitant 80 mg once per day. Primary end point was rate of complete response (ie, no vomiting or rescue treatment) from days 2 to 5 after chemotherapy.. Of 580 enrolled patients, 551 were evaluable: 273 received dexamethasone, and 278 received aprepitant. Day 1 complete response rates were similar: 87.6% for dexamethasone and 84.9% for aprepitant (P < .39). From days 2 to 5, complete response rates were the same with both antiemetic prophylaxes (79.5%; P < 1.00), as were results of secondary end points (ie, complete protection, total control, no vomiting, no nausea, score of Functional Living Index-Emesis; P < .24). Incidences of insomnia (2.9% v 0.4%; P < .02) and heartburn (8.1% v 3.6%; P < .03) were significantly greater with dexamethasone on days 2 to 5.. In patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy and receiving the same antiemetic prophylaxis for acute emesis, dexamethasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Female; Heartburn; Humans; Male; Middle Aged; Morpholines; Nausea; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome; Vomiting

Nausea and vomiting are among the most feared complications of chemotherapy reported by patients. The objective of this study was to establish the overall complete response (CR; no emesis or use of rescue medication 0-120 h after chemotherapy) with either ondansetron- or palonosetron-containing antiemetic regimens in patients receiving highly emetogenic chemotherapy (HEC).. This was a prospective, open-label, randomized, single-center, pilot study that enrolled patients receiving their first cycle of HEC. Patients were randomized to receive either palonosetron 0.25 mg IV (PAD) or ondansetron 24 mg orally (OAD) on day 1 prior to HEC. All patients received oral aprepitant 125 mg on day 1, then 80 mg on days 2 and 3, and oral dexamethasone 12 mg on day 1, then 8 mg on days 2, 3, and 4. Descriptive statistics were used to summarize the data.. A total of 40 patients were enrolled, 20 in each arm. All patients were female, and 39 received doxorubicin/cyclophosphamide chemotherapy for breast cancer. For the primary endpoint, 65 % (95 % CI, 40.8-84.6 %) of patients in the PAD arm and 40 % (95 % CI, 19.1-63.9 %) of patients in the OAD arm achieved an overall CR.. While CR rates for aprepitant and dexamethasone plus palonosetron or ondansetron-containing regimens have been published previously, this is the first documentation of CR rates with these regimens in the same patient population. These results may be used to design a larger, adequately powered, prospective study comparing these regimens.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Ondansetron; Palonosetron; Pilot Projects; Prospective Studies; Quinuclidines; Vomiting

This study evaluated the efficacy and tolerability of aprepitant, dexamethasone, and palonosetron in the prevention of nausea and vomiting in breast cancer patients receiving their initial cycle of doxorubicin and cyclophosphamide (AC).. Patients with breast cancer, ≥ age 18, with a performance status of ≤ 2, receiving doxorubicin (≥ 60 mg/m(2)) and cyclophosphamide (≥ 500 mg/m(2)) for the first time were eligible. Prior to chemotherapy patients received aprepitant 125 mg orally (PO), dexamethasone 8-10 mg PO/intravenously (IV), and palonosetron 0.25 mg IV. On days 2-3, dexamethasone 4 mg PO and aprepitant 80 mg PO were given. Outcomes were recorded in patient diaries for the 120-h study period following chemotherapy. Primary endpoint was the proportion of patients achieving complete response (no emesis or rescue) for the 120-h study period.. Thirty-six patients were enrolled and all are evaluable. The median age was 53 (33-75) and 36 are females. Eighteen patients (50%) achieved a complete response during the 120-h study period. Acute (≤ 24 h) and delayed (24-120 h) complete response rates were 81% (27/36) and 61% (22/36), respectively. No emesis rates for the acute, delayed, and overall study periods were 97% (35/36), 94% (34/36), and 92% (33/36), respectively. Treatment was well tolerated.. The combination of aprepitant, dexamethasone, and palonosetron prevented emesis in more than 90% of breast cancer patients receiving their initial cycle of AC chemotherapy. Nausea was less well controlled. Overall complete response was achieved in one half of the study patients. Further improvement in the prevention of AC-induced chemotherapy-induced nausea and vomiting will require more effective antinausea treatments.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Palonosetron; Pilot Projects; Quinuclidines; Vomiting

The prodrug cyclophosphamide is metabolized by cytochrome P450(CYP)2B6 to the active metabolite, 4-hydroxycyclophosphamide (4-OH), and by CYP3A4/5 to toxic chloracetaldehyde and 2-dechloroethylcyclophosphamide (DCE). Since aprepitant is a moderate inhibitor of CYP3A4, the study was designed to determine whether its concurrent use alters the pharmacokinetics (PK) of cyclophosphamide. In addition, we sought to determine the effect of race and pharmacogenomics on cyclophosphamide PK.. Eighteen patients with localized breast cancer were randomized in this double-blinded cross-over study to receive aprepitant or placebo in addition to cyclophosphamide 600 mg/m(2) and doxorubicin 60 mg/m(2). Blood samples were collected for both PK analysis of cyclophosphamide and metabolites and pharmacogenomic analysis. Single nucleotide polymorphisms genotyped were CYP3A4*1B, CYP3A5*3, and CYP2B6*6.. The geometric mean area under concentration-time curve (AUC(0-t) μg/mL h) for cyclophosphamide was 282 following aprepitant and 230 following placebo (ratio 1.23; 90% CI 1.13, 1.33). 4-OH AUC(0-t) (μg/mL h) was 6.80 following aprepitant and 6.96 following placebo (ratio 0.98; 90% CI 0.88, 1.08). DCE AUC(0-t) (μg/mL h) was 6.76 following aprepitant and 9.37 following placebo (ratio 0.72; 90% CI 0.64, 0.81). Genotype analysis was confounded by race. Race was a significant predictor of DCE lnAUC(0-t) (P = 0.0169) as African Americans had approximately a 2-fold higher DCE AUC than Caucasians.. Aprepitant altered the exposure of cyclophosphamide and DCE but not the active 4-OH metabolite, making it unlikely that aprepitant would change the clinical efficacy of cyclophosphamide. African Americans were also found to have altered PK compared with Caucasian patients.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Black or African American; Breast Neoplasms; Breast Neoplasms, Male; Cross-Over Studies; Cyclophosphamide; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP3A; Double-Blind Method; Doxorubicin; Drug Interactions; Female; Humans; Male; Middle Aged; Morpholines; Oxidoreductases, N-Demethylating; Pharmacogenetics; Polymorphism, Single Nucleotide; White People

A number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis. This post-hoc analysis addressed whether: (1) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection (≥80% no emesis); (2) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk.. Breast cancer patients in a phase III double-blind, placebo-controlled trial were randomized to antiemetic regimens including ondansetron and dexamethasone, or aprepitant, ondansetron, and dexamethasone. Multivariate logistic regression models were used to assess the impact on emesis (but not nausea) of the regimen with aprepitant, and previously reported risk factors, including age (<55 and ≥55 years), ethanol use (0-4 or ≥5 drinks/week), history of pregnancy-related morning sickness, and history of motion sickness, using a modified intent-to-treat approach.. Treatment with aprepitant (P < 0.0001), older age (P = 0.006), ethanol use (P = 0.0048), and no history of morning sickness (P = 0.0007) were all significantly associated with reduced likelihood of emesis. The proportion of patients with one, two, or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control (70.2-82.8% vs. 38.6-66.4%, respectively).. Aprepitant markedly improved control of emesis in patients with one or more risk factors. This analysis did not support using risk factors for modifying the antiemetic approach. A low-risk group with zero risk factors for whom aprepitant provided little benefit was of questionable clinical utility, since they comprised less than 3% of patients.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Breast Neoplasms, Male; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Drug Therapy, Combination; Female; Humans; Logistic Models; Male; Middle Aged; Morpholines; Multivariate Analysis; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Prognosis; Risk Factors; Vomiting

Chemotherapy-induced nausea and vomiting includes both Acute (0-24 h) and Delayed (24-120 h) components with different physiologic mechanisms. A combination of a serotonin antagonist, a corticosteroid, and an NK-1 antagonist has proven effective against this problem. However, standard antiemetic regimens require administration over 3-4 days after chemotherapy. The present study evaluated a more convenient single-day three-drug antiemetic regimen for patients receiving moderately emetogenic chemotherapy.. Chemotherapy-naïve patients with solid tumors receiving cyclophosphamide and/or doxorubicin were eligible. Patients could not have pre-existing etiologies for vomiting. Prior to chemotherapy, patients received a single dose of aprepitant 285 mg p.o., dexamethasone 20 mg p.o., and palonosetron 0.25 mg i.v. A daily patient diary recording episodes of emesis and severity of nausea was then kept for 5 days. Any further antiemetics were considered rescue medication.. Forty-one eligible and evaluable patients (40 women, one man) with breast cancer were entered on study. Most were receiving adjuvant chemotherapy. Complete Response (no vomiting, no rescue medication) was seen in 51% of patients, including 76% with Complete Response for the Acute period and 66% for the Delayed period. No emesis was reported for 100% of patients in the Acute period and 95% in the Delayed period. No Nausea was seen in 32% of patients. No untoward toxicities were seen.. A single-day three-drug antiemetic regimen is feasible and effective for protection against both Acute and Delayed vomiting after moderately emetogenic chemotherapy. Formal comparison to a standard multi-day antiemetic regimen is warranted.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Breast Neoplasms, Male; Chemotherapy, Adjuvant; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Time Factors; Vomiting

To assess the efficacy of adding aprepitant to a 5-HT(3) antagonist and dexamethasone as salvage antiemetic therapy for breast cancer patients receiving their initial cycle of an anthracycline and cyclophosphamide (AC) and failing to achieve complete control of emesis.. Eligibility: breast cancer patients receiving their first cycle of AC.. standard dose of a 5-HT(3) antagonist and dexamethasone 8-10 mg IV/PO on day 1 prior to cycle 1 of AC and dexamethasone 4 mg bid on days 2 and 3. Patients without complete control (no emesis, no nausea, or rescue antiemetics) during cycle 1 could proceed to cycle 2. During cycle 2, patients received AC and identical antiemetics (except dexamethasone 4 mg qd on days 2 and 3) plus aprepitant 125 mg PO day 1 and 80 mg PO days 2 and 3. Primary endpoint: complete control, 0-120 h after chemotherapy.. Sixty-two patients received cycle 1 of AC. Complete control cycle 1: 13 patients (21%; 95%CI, 12-33%). Of the 49 patients eligible for cycle 2, four elected not to continue on study. Of the 45 patients receiving cycle 2, 44 were evaluable. Complete control and complete response (no emesis, no rescue) for the 5-day study period improved from 0% to 18% (p = 0.14) and 7% to 36% (p = 0.02) on cycles 1 and 2, respectively.. In breast cancer patients receiving AC, the addition of aprepitant to a 5-HT(3) antagonist and dexamethasone during cycle 2 of treatment improved antiemetic outcome. Although the improvement in the primary endpoint of complete control during cycle 2 was not significant, all secondary endpoints such as complete response and no emesis rates were significantly better during cycle 2. The extent of antiemetic control during cycle 2 was numerically inferior to the results achieved in a phase III trial employing aprepitant with cycle 1 of AC chemotherapy, suggesting that the preferred approach is to include aprepitant with the initial cycle of AC chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Doxorubicin; Drug Therapy, Combination; Female; Humans; Middle Aged; Morpholines; Nausea; Prospective Studies; Salvage Therapy; Time Factors; Treatment Outcome; Vomiting

This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients.. Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE).. Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048).. The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Carcinoma, Ductal, Breast; China; Dexamethasone; Double-Blind Method; Female; Humans; Middle Aged; Morpholines; Nausea; Ondansetron; Quality of Life; Vomiting

This is the first study in which the NK(1)-receptor antagonist, aprepitant (APR), was evaluated for the prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy.. Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide +/- doxorubicin or epirubicin. Patients were randomly assigned to either an aprepitant regimen (day 1, APR 125 mg, ondansetron (OND) 8 mg, and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, APR 80 qd) [DOSAGE ERROR CORRECTED] or a control regimen (day 1, OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, OND 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary. The primary efficacy end point was the proportion of patients with complete response, defined as no vomiting and no use of rescue therapy, during 120 hours after initiation of chemotherapy in cycle 1. The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis questionnaire.. Of 866 patients randomized, 857 patients (99%) were assessable. Overall complete response was greater with the aprepitant regimen than with the control regimen (50.8% v 42.5%; P = .015). More patients in the aprepitant group reported minimal or no impact of CINV on daily life (63.5% v 55.6%; P = .019). Both treatments were generally well tolerated.. The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Epirubicin; Female; Humans; Middle Aged; Morpholines; Nausea; Ondansetron; Vomiting

Patients receiving the highly emetogenic high-dose chemotherapy regimen with cyclophosphamide, thiotepa and carboplatin (CTC) may benefit from the neurokin-1 receptor antagonist aprepitant in addition to standard anti-emetic therapy. As aprepitant has been shown to be a moderate inhibitor of the cytochrome P450 (CYP) 3A4 isoenzyme, its effect on the pharmacokinetics and metabolism of cyclophosphamide and thiotepa was evaluated. Moreover, preliminary results on the clinical efficacy of aprepitant in the CTC regimen are reported.. Six patients were enrolled in a protocol that employed a 4-day course of CTC high-dose chemotherapy with cyclophosphamide (1,500 mg/m2/day), thiotepa (120 mg/m2/day) and carboplatin (AUC 5 mg min/ml/day). Two patients received the tCTC protocol, which comprises two-third of the dose of CTC. In addition to standard anti-emetic therapy, the patients received aprepitant from one day before the start of their course until 3 days after chemotherapy. Blood samples were collected on days one and three of the course and analyzed for cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide, thiotepa and its main active metabolite tepa. The influence of aprepitant on the pharmacokinetics of cyclophosphamide and thiotepa was analyzed using a population pharmacokinetic analysis including a reference population of 49 patients receiving the same chemotherapy regimen without aprepitant and sampled under the same conditions. The frequency of nausea and vomiting in the six patients receiving CTC was compared with those of the last 22 consecutive patients receiving CTC chemotherapy without aprepitant. Inhibitory activity of aprepitant on cyclophosphamide and thiotepa metabolism was also tested in human liver microsomes.. In our patient population, the rate of autoinduction of cyclophosphamide (P=0.040) and the formation clearance of tepa (P<0.001) were reduced with 23% and 33% when aprepitant was co-administered, respectively. Exposures to the active metabolite 4-hydroxycyclophosphamide and tepa were therefore reduced (5% and 20%, respectively) in the presence of aprepitant. In human liver microsomes, the 50% inhibitory concentrations (IC50) of aprepitant for inhibition of cyclophosphamide (IC50=1.3 microg/ml) and thiotepa (IC50=0.27 microg/ml) metabolism were within the therapeutic range. Patients receiving aprepitant experienced less frequently CINV both during and after the CTC course compared with the reference population (nausea 3.7 days vs. 5.8 days, P=0.052; vomiting 0.5 days vs. 4.8 days, P<0.001).. Aprepitant inhibited both cyclophosphamide and thiotepa metabolism, most probably due to inhibition of the CYP 3A4 and/or 2B6 isoenzymes. The effects of this interaction are, however, small compared to the total variability. Addition of aprepitant may provide superior protection against vomiting in patients receiving the highly emetogenic high-dose CTC chemotherapy.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Carboplatin; Cyclophosphamide; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Female; Humans; Male; Microsomes, Liver; Morpholines; Nausea; Neoplasms, Germ Cell and Embryonal; Thiotepa

Chemotherapy-induced nausea and vomiting are commonly experienced side effects in breast cancer (BCa) patients. Antiemetic drugs used in BCa treatment are either inhibitors or inducers of cytochrome P450 (CYP) enzymes, while anticancer drugs are metabolized by CYPs.. The purpose of the present work was to evaluate in silico drug-drug interaction (DDI) potential between BCa chemotherapeutic drugs and antiemetic agents.. The Drug-Drug Interaction™ module of GastroPlus™ was employed to assess CYP-related interactions between antiemetic and anticancer therapy combinations. The CYP inhibitory or inducing parameters (IC. Analyses of twenty-three BCa drugs indicated that 22% of the chemotherapeutic drugs do not need an antiemetic agent due to their low emetogenicity, whereas 30% of the anticancer drugs are not metabolized by CYPs. The remaining eleven anticancer drugs metabolized by CYPs generated ninety-nine combinations with nine antiemetics. Simulation of DDIs suggest that about half of the pairs did not demonstrate any potential for DDI, whereas 30%, 10%, and 9% of the pairs showed weak, moderate, and strong interaction potential, respectively. In the present study, netupitant was the only antiemetic that showed strong inhibitory interactions (predicted AUC ratio > 5) with CYP3A4-metabolzied anticancer therapies (e.g., docetaxel, ribociclib, olaparib). Moderate to no interactions were observed with ondansetron, aprepitant, rolapitant, and dexamethasone in combination with anticancer agents.. It is critical to recognize that these interactions can get amplified in cancer patients because of the severity of the disease and chemotherapy toxicities. Clinicians need to be aware of the DDI likelihood of the drug combinations used in BCa treatment.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Drug Interactions; Female; Humans

Numerous molecules have been introduced to participate in the formation of breast cancer, the most common malignancy in women. Among them, neuropeptide substance P (SP) and its related receptor neurokinin-1 receptor (NK1R) have attracted unprecedented attention in tumorigenesis processes. In this study, we investigated the effect of the SP/NK1R pathway on the induction of oxidative stress in breast cancer and examine the therapeutic potential of NK1R inhibition in this malignancy.. MCF-7 cells were treated with varying concentrations of SP and aprepitant, an FDA-approved NK1R antagonist, either as a single drug or in a combined modality. Resazurin assay was used to evaluate the anti-cancer ability of aprepitant. The alteration in the intracellular levels of reactive oxygen species (ROS) and gene expression were determined using ROS assay and the qRT-PCR analysis, respectively.. The stimulation of the SP/NK1R axis in the MCF-7 cells was coupled with the accumulation of ROS as well as upregulation of NF-κB and its related pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and IL-6. In contrast, the suppression of NK1R by aprepitant halted the viability of MCF-7 cells, at least partly due to p53-mediated upregulation of p21. Moreover, aprepitant attenuated the oncogenic properties of SP by preventing the oxidative property of this neuropeptide.. Overall, our results suggest that the SP/NK1R pathway might play a critical role in breast cancer pathogenesis, probably through inducing ROS/NF-κB-mediated inflammatory responses. Moreover, it seems that blockage of the axis has promising therapeutic value against breast cancer cells. Schematic representation proposed for the plausible mechanism by which the stimulation of the SP/NK1R might induce oxidative stress in breast cancer-derived MCF-7 cells. Once SP interacts with NK1R, this signaling axis could disturb the balance between the expression of p53 and NF-κB, an event that leads to the accumulation of ROS within MCF-7 cells. The produced ROS, in turn, elevates the expression of pro-inflammatory cytokines (TNF-α and IL-6) and downregulates the expression of p21. On the other hand, aprepitant, an antagonist of NK1R, could reduce the survival of proliferative capacity of MCF-7 cells by decreasing the intracellular levels of ROS and p53-mediated up-regulation of p21. Along with the effect on p53, aprepitant could also reduce the expression of NF-κB and its related pro-inflammatory cytokines.

Topics: Aprepitant; Breast Neoplasms; Cell Proliferation; Cytokines; Female; Humans; Interleukin-6; NF-kappa B; Reactive Oxygen Species; Receptors, Neurokinin-1; Substance P; Tumor Suppressor Protein p53

Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant - a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

Topics: Aprepitant; Breast Neoplasms; Cyclophosphamide; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome

TGFβ promotes cancer aggressiveness in advanced stages. NK1R-Tr expression in advanced breast cancer has a pro-carcinogenic effect. In this study, we aimed to investigate the effect of the association of TGFβ with NK1R-Tr expression on the proliferation and apoptosis of breast cancer cells.. Immunohistochemical staining and Western blot analysis were used to detect TGFβ and NK1R-Tr in breast cancer and paracancerous tissue samples. MDA-MB-231 and BT549 cells were stimulated with TGFβ after NK1R knockdown or treated with the NK1R antagonist aprepitant, and the effects of TGFβ and NK1R-Tr on proliferation and apoptosis were detected by CCK-8, colony formation and flow cytometry assays. In vivo xenograft models were used to further verify the effects of NK1R-Tr and TGFβ. The regulatory effects of Smad4 on NK1R promoter activity were confirmed by ChIP and dual-luciferase reporter assays.. The expression levels of TGFβ and NK1R-Tr were higher in breast cancer tissues than in adjacent tissues and were positively correlated in human breast cancer tissues. NK1R knockdown or aprepitant treatment in MDA-MB-231 and BT549 cells attenuated the effects of TGFβ on cell proliferation. The proportion of cells in G2/M phase significantly increased, the expression of cyclin B1 decreased, and the expression of P21 increased; these effects were weakened by TGFβ treatment. Apoptosis in breast cancer cells was significantly increased. In vivo xenograft models were used to further verify that NK1R-Tr and TGFβ promoted tumour growth. After TGFβ treatment, the binding capacity of Smad4 to the NK1R promoter, as well as luciferase activity, was enhanced.. The expression levels of TGFβ and NK1R-Tr were higher in breast cancer tissues than in normal tissues, and both were correlated with a poor patient prognosis. TGFβ and NK1R-Tr promoted cell proliferation and inhibited apoptosis, and TGFβ regulated the expression of NK1R-Tr via Smad4.

Topics: Animals; Apoptosis; Aprepitant; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Smad4 Protein; Transforming Growth Factor beta; Xenograft Model Antitumor Assays

We aimed to investigate the efficacy of 0.25 mg dose of palonosetron and granisetron in triplet antiemetic prophylaxis in breast cancer patients receiving HEC.. Patients with nonmetastatic breast cancer who received HEC [doxorubicin or epirubicin plus cyclophosphamide (AC/EC)] were enrolled in the study. The prophylactic triplet antiemetic regimens were used according to the doctor's preference during the first cycle of HEC as intravenous dexamethasone and palonosetron 0.25 mg or granisetron 3 mg on day 1 as well as oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3).The primary endpoint was complete response rate (CR) on acute and delayed chemotherapy-induced nausea and vomiting (CINV), separately.. A total of 118 female patients were included in the study. Patients received AC (83%), EC (3%), and dose-dense AC (14%) as adjuvant (88%) or neoadjuvant (12%). The majority of patients received palonosetron (59%) containing antiemetic treatment. The CR rate on acute and delayed vomiting was very high and not statistically different in both of the arms (acute 87% vs. 96%, p = 0.089; delayed 90% vs. 92%, p = 0.489), respectively. Nevertheless, the CR rate on either acute or delayed nausea was lower than vomiting (acute 51% vs. 51%; delayed 38% vs. 29%, p = 0.203; respectively).. This is the second study that compared a 0.25 mg dose of palonosetron with first-generation setron in triplet antiemetic prophylaxis in cancer patients receiving HEC. We could not find meaningful statistical differences between two arms, regarding CR rate on acute and delayed CINV.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Epirubicin; Female; Granisetron; Humans; Middle Aged; Nausea; Palonosetron; Prospective Studies; Vomiting

Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV.. We evaluated CINV attributable to anthracycline-based chemotherapy in Japanese breast cancer patients treated with an antiemetic regimen that included palonosetron, aprepitant, and dexamethasone. Furthermore, we investigated the associations between CINV and single nucleotide polymorphisms in 6 candidate genes.. Emesis episodes were rarely observed in the 125 patients included in the present survey (7.2%; n = 9); however, significant nausea occurred in more than one half of the patients (52.8%; n = 66). In particular, acute significant nausea was not effectively controlled. Multivariate logistic regression analysis revealed that the ABCG2 (rs2231142) AA genotype is significantly associated with acute significant nausea (odds ratio, 4.87; 95% confidence interval, 1.01-23.60; P = .049).. The findings of the present study provide significant insights for developing personalized antiemetic strategies for breast cancer patients receiving anthracycline-based chemotherapy.

Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Antiemetics; Aprepitant; ATP Binding Cassette Transporter, Subfamily G, Member 2; Breast Neoplasms; Dexamethasone; Female; Genetic Predisposition to Disease; Humans; Middle Aged; Nausea; Neoplasm Proteins; Odds Ratio; Palonosetron; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors; Treatment Outcome; Vomiting

This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with breast cancer treated with anthracycline. We retrospectively analyzed data from Japanese patients with breast cancer, who had received their first cycle of anthracycline and were treated with aprepitant, palonosetron, and dexamethasone with or without olanzapine. This retrospective observational study was performed at Ehime University Hospital using the electronic medical records. Multivariable and propensity score-adjusted analyses were performed to compare the onset of complete response (CR) failure between the groups. One-hundred and thirty patients were included in this study and the four- and three-drug group had 22 and 108 patients, respectively. Similar to multivariable logistic regression analysis, propensity-adjusted logistic regression analysis revealed that the four-drug group was markedly associated with a decreased odds of CR failure in the overall, acute, and delayed phases (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10-0.73; OR: 0.28, 95% CI: 0.10-0.76; and OR: 0.15, 95% CI: 0.04-0.57, respectively). Additionally, treatment-related adverse events were well tolerated in both the groups. These findings suggest that the antiemetic efficacy of the four-drug combination is superior to that of the standard three-drug combination.

Topics: Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Dexamethasone; Drug Therapy, Combination; Female; Humans; Incidence; Middle Aged; Nausea; Olanzapine; Palonosetron; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome; Vomiting

The aim of this study was to identify a high-risk or low-risk population for chemotherapy-induced nausea and vomiting among patients with breast cancer treated with a current standard 3-drug antiemetic regimen and receiving anthracycline.. We analyzed data from chemotherapy-naive Japanese patients with breast cancer, who had received the first cycle of anthracycline-based regimen and were treated with a 3-drug combination of aprepitant, palonosetron, and dexamethasone. This study was carried out at Ehime University Hospital (Toon, Japan) using electronic medical records from May 2011 to June 2017. The primary end point was complete response (CR), which was defined as no emesis and no use of rescue medication.. A total of 103 patients were included in this study. The percentages of patients who had a CR in the overall, acute, and delayed phases were 35.0%, 40.8%, and 50.5%, respectively. Multivariate logistic regression analysis revealed that age <55 years and body mass index <27.5 kg/m. The present findings suggest that, among patients with breast cancer receiving anthracycline and treated with aprepitant, palonosetron, and dexamethasone, patients younger than 55 years and having a body mass index <27.5 kg/m

Topics: Anthracyclines; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Dexamethasone; Female; Humans; Middle Aged; Nausea; Palonosetron; Retrospective Studies; Risk Factors; Vomiting

Radiotherapy-induced nausea and vomiting (RINV) is a toxicity that can occur in 40-80% of individuals who receive radiation treatment. Current guidelines recommend 5-hydroxytryptamine3 receptor antagonists (5-HT3 RAs) for prophylaxis of RINV for moderate and highly emetogenic radiotherapy; however, certain patients may suffer from RINV despite prophylaxis.. This report details the case of a 47-year-old female with extensive bony involvement to the spine from breast cancer presenting with lower back pain.. To palliate her symptoms, the patient underwent a course of irradiation to the lumbar spine and was prescribed ondansetron as an antiemetic. However, the patient experienced severe nausea and emesis and was subsequently switched to granisetron and aprepitant.. The patient completed the remainder of the radiation treatment with no further emesis and minimal nausea, representing the first documented success of granisetron and aprepitant for RINV after failure on ondansetron.. In chemotherapy, switching 5-HT3 RAs after failure on the first is successful in preventing chemotherapy-induced nausea and vomiting (CINV), yet this has not been previously reported in radiation. In this patient, granisetron and aprepitant were successful in substantially reducing nausea and preventing further emesis, and may represent an alternative antiemetic regimen for RINV prophylaxis and salvage.

Topics: Antiemetics; Aprepitant; Bone Neoplasms; Breast Neoplasms; Female; Granisetron; Humans; Middle Aged; Morpholines; Nausea; Neoplasm Metastasis; Ondansetron

The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy.. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given.. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE.. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Humans; Infusions, Intravenous; Middle Aged; Morpholines; Nausea; Phlebitis; Retrospective Studies; Vomiting

The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in the development of cancer. No in-depth studies of the involvement of this system in breast cancer (BC) have been carried out, and the action exerted by the drug aprepitant on BC cells is currently unknown. We show the involvement of this system in human BC cell lines: i) these cells express mRNA for the NK-1 receptor; ii) they overexpress NK-1 receptors; iii) the NK-1 receptor is involved in their viability; iv) SP induces their proliferation; v) NK-1 receptor antagonists block SP-induced mitogen stimulation of these cells; vi) the specific antitumor action of such antagonists on these cells occurs through the NK-1 receptor; and vii) BC cell death is due to apoptosis. We also found NK-1 receptors and SP in all human BC samples studied. The NK-1 receptor may be a promising target in the treatment of BC and NK-1 receptor antagonists could be candidates as a new antitumor drug in the treatment of BC.

Topics: Antineoplastic Agents; Aprepitant; Breast Neoplasms; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; MCF-7 Cells; Morpholines; Neurokinin-1 Receptor Antagonists; Piperidines; Receptors, Neurokinin-1; Substance P; Tryptophan

We retrospectively analyzed the efficacy and safety of aprepitant in breast cancer patients who were treated with FEC(5- fluorouracil, epirubicin, cyclophosphamide)or EC(epirubicin, cyclophosphamide). We divided patients into two groups according to the aprepitant approval period. The rate of severe nausea(@Grade 2)was significantly less in patients with aprepitant(acute 10. 0%, delayed 15. 0%)than those without aprepitant(acute 29. 1%, delayed 30. 9%). Complete response( no vomiting and no use of rescue therapy)in the acute phase was significantly higher in the aprepitant pretreated group than in the no aprepitant group(82. 5% vs 61. 8%, respectively). Moreover, complete response in the delayed phase was also higher in the aprepitant group than in the no aprepitant group(82. 5%vs 58. 2%, respectively). Pre-treatment with aprepitant did not increase adverse events including constipation and elevation of alanine transaminase. The aprepitant was effective in terms of prevention of chemotherapy-induced nausea and vomiting in patients treated with an anthracycline- based regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Epirubicin; Female; Fluorouracil; Humans; Middle Aged; Morpholines; Nausea; Retrospective Studies

Topics: Antiemetics; Antineoplastic Agents, Alkylating; Aprepitant; Breast Neoplasms; Cyclophosphamide; Drug Interactions; Female; Humans; Morpholines; Neurokinin-1 Receptor Antagonists