aprepitant and Genital-Neoplasms--Female

The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK. We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1-4) combined with NK. Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0-24 h) and delayed phases (24-120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ.. Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy.

Topics: Adult; Aged; Antiemetics; Aprepitant; Carboplatin; Dexamethasone; Female; Genital Neoplasms, Female; Granisetron; Humans; Middle Aged; Nausea; Olanzapine; Vomiting

This trial is an open-label, single-arm, multicentre phase II trial. Patients who receive CBDCA (AUC ≥4)-based therapy and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive OLZ (5 mg oral administration on days 1-4, after supper) in combination with 5-HT. The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.. UMIN000031646.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Dexamethasone; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Granisetron; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequently encountered side effects of cancer treatment. Severe CINV can lead patients to refuse chemotherapy, which ultimately affects cancer outcomes. The development of fairly new antiemetic agents, 5-hydroxytryptamine-3 receptor antagonists, palonosetron and neurokinin-1 receptor antagonists and aprepitant has reduced the risk and incidence of CINV. In this study, we assessed the efficacy of aprepitant plus palonosetron against palonosetron for CINV in patients receiving moderately emetic cancer chemotherapy (paclitaxel and carboplatin combination [TC] therapy).. Between November 2010 and March 2014, 78 patients with gynecological cancer treated with TC therapy were randomized into two groups: an aprepitant group (administered aprepitant, dexamethasone and palonosetron) and a control group (administered dexamethasone and palonosetron). The primary study endpoint was complete response, defined as the complete absence of emetic events in the delayed phase.. The complete response rate in the delayed phase differed significantly between the two groups, with 82% in the aprepitant group and 97% in the control group (P = 0.025).. The combination of aprepitant and palonosetron appears to be of greater efficacy than palonosetron alone for the prevention of delayed-phase CINV induced by TC therapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Outcome Assessment, Health Care; Paclitaxel; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC.. This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy.. Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events.. Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Palonosetron; Prospective Studies; Quinuclidines; Serotonin Antagonists; Vomiting

The purpose of this pilot study was to compare the response rates and daily living activities of patients with newly diagnosed gynecologic cancer treated with fosaprepitant or aprepitant in the management of chemotherapy-induced nausea and vomiting.. Eligible participants were randomized to either intravenous fosaprepitant (150 mg, day 1) or oral aprepitant (125 mg on day 1 and 80 mg on days 2-3) before undergoing weekly paclitaxel (80 mg/2)(2) and monthly carboplatin (AUC 6)-based chemotherapy. In addition, standard premedications (eg, ranitidine, dexamethasone, and diphenhydramine) were administered intravenously on day 1. Response evaluation and impact on daily life were measured throughout the acute phase (0-24 hours), delayed period (days 2-4), and overall phase (0-120 hours) of the patients' initial chemotherapy cycle via the Functional Living Index-Emesis.. In the current investigation, 20 gynecologic cancer subjects were treated with either fosaprepitant (n = 10) or aprepitant (n = 10) before their first chemotherapy cycle. We observed 7 overall complete responses (70%, no emetic episodes or rescue medications) in the aprepitant group and 6 (60%) in the fosaprepitant cohort (P = 0.660). In addition, both treatment groups reported similarly, favorable rates of daily living activities throughout the acute (P = 0.626) and delayed (P = 0.648) phases of cycle 1 chemotherapy.. The findings from the current analysis suggest that intravenous fosaprepitant and oral aprepitant confer beneficial antiemetic prevention. Moreover, the 2 medications theoretically afford a favorable impact on daily living, thereby potentially facilitating the completion of a patient's clinically prescribed chemotherapy regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Genital Neoplasms, Female; Humans; Middle Aged; Morpholines; Nausea; Pilot Projects; Vomiting

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.. 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.. 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.. 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.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Dexamethasone; Double-Blind Method; Drug Hypersensitivity; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Middle Aged; Morpholines; Nausea; Paclitaxel; Remission Induction; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

This study aimed to evaluate the efficacy of aprepitant, a neurokinin (NK)1 receptor antagonist, on chemotherapy-induced nausea and vomiting (CINV).. A randomized, open-labeled, parallel-design study was undertaken in gynecologic-cancer (GC) patients at the Fukuoka University Hospital. Twenty-three patients were divided into without (group A) or with aprepitant (Group B) in the first cycle of paclitaxel and carboplatin (TC) therapy. From the second cycle onwards, all patients used aprepitant. Statistical significance was assessed using McNemar and Chi-square tests.. In the first cycle, the prevalence of a complete response, no episodes of nausea or food intake in group B was significantly increased compared to group A. No significant difference in the prevalence of a complete response or food intake situation was found from the second cycle onwards.. Combination of aprepitant with standard anti-emetic therapy may contribute to prevention of CINV in TC therapy for GC patients.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Female; Genital Neoplasms, Female; Humans; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Paclitaxel; Treatment Outcome; Vomiting

There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT₃ receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC.. We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT₃ receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT₃ receptor and dexamethasone with/without aprepitant.. When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT₃ receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT₃ receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001).. The addition of aprepitant therapy was more effective than the control therapy of a 5-HT₃ receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Cross-Over Studies; Diet; Drug Administration Schedule; Female; Genital Neoplasms, Female; Granisetron; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Paclitaxel; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥ 50 mg/m(2)).. Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy).. Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each).. Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Prospective Studies; Quality of Life; Quinuclidines; Vomiting

This study was conducted to evaluate the efficacy and the difference in effects of the oral neurokinin-1(NK-1) receptor antagonist aprepitant for chemotherapy-induced nausea/vomiting (CINV) in Japanese patients with gynecological cancer receiving highly emetogenic (cisplatin) and moderately emetogenic (carboplatin) chemotherapy.. Aprepitant was added during the second course of chemotherapy in Japanese patients with grade ≥ 2 (Common Terminology Criteria for Adverse Events, version 3.0) nausea and vomiting during the first course despite receiving antiemetic therapy (a first-generation 5-hydroxytryptamine 3 receptor antagonist + dexamethasone), and in patients who requested stronger antiemetic therapy despite only having grade 1 nausea and vomiting. The incidence of nausea and vomiting was compared between the first and second courses in each group.. Ninety-six (55.5%) out of 173 patients received add-on therapy with aprepitant. There was a significant increase in the complete response (CR: no vomiting or salvage therapy) rate in the patients receiving aprepitant, with marked improvement being confirmed for delayed CINV. Stratified analysis showed that patients with delayed CINV treated with carboplatin had a significantly higher CR rate, while patients with both acute and delayed CINV treated with cisplatin had significantly higher CR rates. There was a positive correlation between the incidence of nausea and the incidence of vomiting in the patients treated with aprepitant.. The oral NK-1 receptor antagonist aprepitant could be effective for both acute and delayed CINV with cisplatin and for delayed CINV with carboplatin in Japanese gynecological cancer patients.

Topics: Adult; Aged; Antineoplastic Agents; Aprepitant; Carboplatin; Cisplatin; Female; Genital Neoplasms, Female; Humans; Japan; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Outcome Assessment, Health Care; Vomiting

There is no positive evidence for the efficacy of antiemetic triplet therapy with aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) for moderate emetogenic chemotherapy, especially for gynecologic malignancies. Thus, the present study evaluated the efficacy of this triplet therapy in patients receiving carboplatin and paclitaxel (CP) for gynecologic malignancy.. Seventy patients with gynecologic cancer receiving CP were enrolled into a prospective single-arm study with APR (125 mg on day 1, 80 mg on days 2-3), PALO (0.75 mg), and DEX (20 mg) before initiating chemotherapy. The primary endpoint was delayed complete response (CR) rate, i.e., no vomiting and no rescue, at 24-120 h after chemotherapy administration.. Seventy patients were enrolled. The delayed CR rate was 97.1% (68/70). No serious adverse events were observed. Younger patient age (≤50 years) tended to be associated with a poor delayed CR rate.. This study demonstrated a notable efficacy of antiemetic triplet therapy with APR, PALO, and DEX in female patients receiving CP. Further evaluation with a larger phase III trial is warranted.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Dexamethasone; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Morpholines; Nausea; Paclitaxel; Palonosetron; Prospective Studies; Quinuclidines; Vomiting; Young Adult