aprepitant and Ovarian-Neoplasms

BACKGROUND The aim of this study was to evaluate the antiemetic effect of aprepitant and to determine how to provide triple combination therapy (aprepitant/azasetron/dexamethasone) to women receiving paclitaxel/carboplatin moderately emetogenic chemotherapy (MEC). MATERIAL AND METHODS The current study was a prospective study of 163 women with gynecologic cancers. We compared the digestive symptoms scores (nausea, vomiting, appetite loss, and dietary intake) of 37 women with ovarian cancers before and after aprepitant administration. We also compared these symptoms in women who underwent 193 cycles of triple combination therapy with symptoms of women who underwent 226 cycles of double combination therapy. For triple combination therapy, azasetron, dexamethasone (reduced dose: 40% of 20 mg), and aprepitant (125 mg) were administered on Day 1, followed by only aprepitant (80 mg) administration on Days 2 and Day 3. RESULTS In 37 women with ovarian cancer, three symptoms, nausea, appetite loss, and dietary intake, were significantly improved by primarily adding aprepitant to double combination therapy in the delayed phase of MEC. Upon comparing their digestive symptoms in all cycles, however, these three symptoms were not significantly different in the delayed phase. Furthermore, all four symptoms in all cycles were worse following triple combination therapy than following double combination therapy in the acute phase (p<0.02). The control of digestive symptoms was generally insufficient without the administration of dexamethasone. CONCLUSIONS Primary aprepitant as an addition to MEC demonstrated efficacy in improving digestive symptoms in the delayed phase. However, its effect may decrease with repeated use. To improve the antiemetic effect, the dose reduction of dexamethasone should be restricted on Day 1 and dexamethasone should be used throughout the delayed phase as well.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Bridged Bicyclo Compounds, Heterocyclic; Carboplatin; Dexamethasone; Female; Humans; Middle Aged; Morpholines; Nausea; Ovarian Neoplasms; Oxazines; Paclitaxel; Pre-Exposure Prophylaxis; Prospective Studies; Vomiting

Women with ovarian carcinoma that are treated with paclitaxel/carboplatin are particularly susceptible to chemotherapy-induced nausea and vomiting (CINV). The current study evaluated the new combination (aprepitant/ramosetron/dexamethasone, 20 mg) in ovarian cancer patients receiving multiple cycles of paclitaxel/carboplatin.. This is a prospective non-randomized single site study. Patients received the following regimen for the prevention of CINV-day 1, 125 mg aprepitant, 0.6 mg ramosetron, and 20 mg dexamethasone before chemotherapy; and days 2-3, 80 mg aprepitant each day. The primary end point was the proportion of patients with complete response (CR) during the 120 h following the first chemotherapy cycle. Toxicity assessments were conducted using the NCI-CTC investigator guide (version 3.0).. Of the 89 patients enrolled, 85 patients were evaluable for efficacy and toxicity, and 68 (80 %) completed all 6 cycles. In cycle 1, the percentage of patients who achieved CR in the acute, delayed, and overall phases was 98.8 %, 89.4 %, and 89.4 %, respectively. Of the 460 cycles, adverse events, drug-related adverse events, and serious adverse events occurred in 179 (38.9 %), 35 (7.6 %), and 10 cycles (2.2 %), respectively. The most common adverse event was constipation (12.4 %) and headache (11.1 %). None of the patients discontinued the study because of adverse events.. The combination of aprepitant, ramosetron, and high-dose dexamethasone demonstrated efficacy for CINV prevention in ovarian cancer patients receiving paclitaxel and carboplatin.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzimidazoles; Carboplatin; Dexamethasone; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Morpholines; Nausea; Ovarian Neoplasms; Paclitaxel; Prospective Studies; Vomiting; Young Adult

We evaluated the efficacy of aprepitant plus granisetron and an increased dose of dexamethasone in selected patients undergoing moderately emetogenic chemotherapy (MEC).. 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.. 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.. 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.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Camptothecin; Carboplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Endometrial Neoplasms; Female; Granisetron; Humans; Irinotecan; Logistic Models; Middle Aged; Morpholines; Neoplasms; Ovarian Neoplasms; Temperance; Treatment Outcome; Vomiting

The purpose of this study was to determine the efficacy of adding a 7-day aprepitant schedule to a 5HT3 receptor antagonist and dexamethasone for patients with germ cell tumors receiving first-line 5-day cisplatin-based chemotherapy.. In a single-arm, open-label, multi-center, phase 2 trial, chemo-naive patients received aprepitant 125 mg PO (per oral) on day 1 and 80 mg PO on days 2 to 7, a 5HT3 receptor antagonist on days 1 to 5, and dexamethasone 8 mg on days 1 to 8. The primary endpoint was no emesis (vomiting or dry retching) during days 1 to 7 of cycle 1.. Fifty patients were recruited. For cycle 1, proportions reporting no emesis on day 1, no emesis on days 1 to 7, no nausea on day 1, and no nausea on days 1 to 7 were 96, 82, 71, and 27%, respectively. The efficacy was maintained in all cycles with over 80% of patients reporting no emesis on any given day of any given cycle. Emesis was more common on days 4 to 7 (68% episodes) than on days 1 to 3 (32% episodes). Over any 24-h period, 49% of patients with emesis reported no more than two episodes, and 62% of patients with nausea reported intensity as 3 or less on a scale from 0 to 10. There were no unexpected or serious adverse events reported.. Adding 7 days of aprepitant to a 5HT3 receptor antagonist and dexamethasone effectively controlled acute and delayed emesis with 5-day cisplatin regimens. Days of nausea were more common than days of vomiting.

Topics: Administration, Oral; Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Mediastinal Neoplasms; Middle Aged; Morpholines; Nausea; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Retroperitoneal Neoplasms; Serotonin 5-HT3 Receptor Antagonists; Testicular Neoplasms; Treatment Outcome; Vomiting; Young Adult

Substance P (SP) has a crucial role in cancer initiation and progression via binding to its specific receptor (NK1R). Various evidence confirmed the overexpression of NK1R and SP in the tissue of multiple cancers, including ovarian cancer. Despite numerous studies, the mechanism of the SP/NK1R system on migration and angiogenesis of ovarian cancer cells has not yet been deciphered. In this study, considering the critical factors in cell migration (MMP-2, MMP-9) and angiogenesis (VEGF, VEGFR), we investigated the possible mechanism of this system in inducing migration and angiogenesis of ovarian cancer cells.. First, the resazurin assay was conducted to evaluate the cytotoxic effect of aprepitant (NK1R antagonist) on the viability of A2780 ovarian cancer cells. After that, the impact of this system and aprepitant on the mRNA expression of the factors mentioned above were studied using RT-PCR. Besides, the scratch assay was performed to confirm the effect of the SP/NK-1R system and aprepitant on cell migration. Our results implied that this system induced cell migration and angiogenesis by increasing the mRNA expression of MMP-2, MMP-9, VEGF, and VEGFR. The obtained results from the scratch assay also confirmed the positive effect of this system on cell migration. Meanwhile, the blocking of NK1R by aprepitant suppresses the SP effects on cell migration and angiogenesis.. Overall, the SP/NK1R system plays a vital role in ovarian cancer progression, and the inhibition of NK1Rusing aprepitant could inhibit the spread of ovarian cancer cells through metastasis and angiogenesis.

Topics: Aprepitant; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Female; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neovascularization, Pathologic; Ovarian Neoplasms; Receptors, Neurokinin-1; Receptors, Vascular Endothelial Growth Factor; RNA, Messenger; Substance P; Vascular Endothelial Growth Factor A

Ovarian cancer is the seventh most common cancer globally, and the second most common cancer among women with significant mortality. Toward this end, it is shown that substance P (SP) is involved in tumor initiation and progression through the neurokinin-1 receptor (NK1R). However, the exact molecular mechanism of the SP/NK1R system in ovarian cancer is not yet fully clarified. In this in vitro study, we decided to investigate the effect of the SP/NK1R system and blockage of NK1R by its specific antagonist (Aprepitant) on the proliferation of ovarian cancer cells as well as the alteration of inflammatory pathways. Our results revealed that Aprepitant stimulated apoptotic cell death and attenuated inflammation of ovarian cancer cells through the NF-kB and P53 signaling pathways. After treatment with Aprepitant, the expression of downstream anti-apoptotic genes related to the NF-kB pathway (survivine and bcl2) was decreased. However, we indicated the positive effect of SP on the proliferation of ovarian cancer cells by inducing the expression of NF-kB protein and NF-kB anti-apoptotic target genes. Moreover, Pro-apoptotic p53 target genes (P21 and Bax) were increased through aprepitant treatment, while SP attenuated these genes' expression. Besides, ROS generation in ovarian cancer cells after treatment with SP induced, while blocking of NK1R with Aprepitant reduced the level of ROS generation. Given this, our data suggest that this NK1R might be used as an important therapeutic target in ovarian cancer and Aprepitant could be considered a new drug in ovarian cancer therapy.

Topics: Apoptosis; Aprepitant; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Female; Humans; NF-kappa B; Ovarian Neoplasms; Reactive Oxygen Species; Receptors, Neurokinin-1; Substance P; Tumor Suppressor Protein p53