palonosetron and Headache

We performed a systematic review and meta-analysis to compare treatment effectiveness and adverse effects in cancer patients receiving chemotherapy with palonosetron to prevent chemotherapy-induced nausea and vomiting (CINV).. We identified randomized controlled clinical trials (RCT) comparing palonosetron with first-generation 5-HT3RA in the prevention of CINV in cancer patients. Meta-analyses were performed on homogeneous studies. Fixed or random-effects models were used to combine data.. Eight eligible trials were identified, reporting outcomes on 3,592 patients. Meta-analyses showed statistically significant differences in favor of palonosetron compared with first-generation 5-HT3RA in prevention of acute CINV (p = .0003), delayed CINV (p < .00001), and overall phase of CINV (p < .00001). Subgroup analyses showed statistically significant differences in favor of both 0.25 mg and 0.75 mg of palonosetron in prevention of all phases of CINV. There were no statistically significant differences between 0.25 and 0.75 mg of palonosetron. Compared with the first-generation 5-HT3RA, 0.75 mg of palonosetron showed a statistically significant difference in the occurrence of constipation (p = .04).. The use of palonosetron should be considered an integral part of adjuvant therapy for prevention of the acute, delayed, and overall phases of CINV. The 0.25 mg intravenous palonosetron dose is as effective as the 0.75 mg intravenous palonosetron dose. However, 0.75 mg intravenous palonosetron causes constipation more frequently than the first-generation 5-HT3RA.

Topics: Adult; Antiemetics; Antineoplastic Agents; Constipation; Dexamethasone; Headache; Humans; Infusions, Intravenous; Isoquinolines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

The effectiveness of palonosetron without delayed dexamethasone dosing against emesis was investigated in patients scheduled to receive the corticosteroid-containing combination of doxorubicin and paclitaxel (AT) for 3 cycles.. Chemo-naïve women with breast cancer receiving doxorubicin (60 mg/m(2)) and paclitaxel (200 mg/m(2)) were eligible. Patients received palonosetron 0.25 mg intravenously before chemotherapy, however, all patients also received a premedication consisting of prednisone (25 mg orally the evening before therapy) and hydrocortisone (250 mg intravenously just before paclitaxel). The primary end point was complete control (CC; no vomiting, no rescue anti-emetics, and no more than mild nausea) during the overall phase (days 1-5) following cycle 1.. Seventy-six patients were enrolled and evaluable (median age 50 years). Fifty-six patients (74%; 95% CI 62-83%) achieved overall CC. Acute (day 1) and delayed (days 2-5) CC rates were 78 and 74%, respectively. No vomiting rates for the acute, delayed and overall phases were 85, 85 and 83%, respectively. An exploratory analysis showed only a small decrease in the probability of achieving CC between cycle 1 (74%) and cycle 3 (66%).. The dexamethasone-sparing strategy prevented emesis in more than 70% of breast cancer patients receiving their initial cycle of AT chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma; Constipation; Dexamethasone; Doxorubicin; Female; Headache; Humans; Isoquinolines; Middle Aged; Nausea; Paclitaxel; Palonosetron; Quinuclidines; Serotonin Antagonists; Time Factors; Treatment Outcome; Vomiting; Young Adult

Chemotherapy-induced nausea and vomiting remain among the most feared adverse effects for cancer patients.. The aim of this study was to evaluate the efficacy and safety of a combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in patients receiving multiple-day cisplatin-based chemotherapy.. Forty-one solid cancer patients received aprepitant, palonosetron and dexamethasone during a 3-day cisplatin-based chemotherapy. Primary end-point was complete response in the overall phase (day 1 until 5 days after the end of chemotherapy).. Aprepitant in combination with palonosetron and dexamethasone was safe, with hiccups (31.7%), fatigue (17.1%), headache (14.6%) and constipation (12.2%) the most common treatment-related adverse events, mostly mild. Complete response was seen in 58.5% of patients in the overall phase. In 23 patients receiving aprepitant in combination with palonosetron and dexamethasone more than one cycle (range: 2-5 cycles), the cumulative emetic protection rate after five cycles was 0.82.. This study shows aprepitant in combination with palonosetron and dexamethasone is safe and effectively controls chemotherapy-induced nausea and vomiting in patients undergoing 3-day cisplatin-based chemotherapy, moreover, the efficacy is maintained during multiple cycles.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Constipation; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Fatigue; Female; Headache; Hiccup; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Prospective Studies; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

Palonosetron is a potent, selective 5-HT(3) receptor antagonist effective in the prevention of acute and delayed chemotherapy-induced nausea and vomiting. In practice, 5-HT(3) receptor antagonists, including palonosetron, are often coadministered with dexamethasone over approximately 15 minutes, although the approval of palonosetron was based on administration as a 30-second infusion. This open-label, randomized, 2-way crossover trial compared the pharmacokinetics and safety of palonosetron 0.25 mg administered as a 15-minute 50-mL intravenous infusion with a 30-second 5-mL infusion. Aside from an anticipated 40% decrease in maximum plasma concentration after a 15-minute infusion, the pharmacokinetics of palonosetron (including area under the plasma concentration-time curve [AUC], plasma elimination half-life, total body clearance, and apparent volume of distribution at steady state) were similar for both treatments. Both treatments were well tolerated, with no significant changes in vital signs or electrocardiograms. Palonosetron infused over 15 minutes is well tolerated, with an AUC(0-infinity) equivalent to a 30-second infusion.

Topics: Adolescent; Adult; Area Under Curve; Biological Availability; Cross-Over Studies; Female; Half-Life; Headache; Humans; Infusions, Intravenous; Isoquinolines; Male; Metabolic Clearance Rate; Middle Aged; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Time Factors

Palonosetron (Aloxi, Onicit) is a selective 5-HT(3) receptor antagonist recently approved by the Food and Drug Administration for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. This study was performed to determine the pharmacokinetics and assess the safety and tolerability of intravenous (IV) palonosetron in healthy U.S. and Japanese subjects. Subjects were administered a single IV dose of palonosetron, ranging from 0.3 to 90 microg/kg in either of two randomized, double-blind, placebo-controlled, ascending-dose studies (n = 80 and n = 32, respectively). Serial blood samples were obtained in both studies to evaluate the pharmacokinetics of palonosetron and its N-oxide metabolite, M9. Intravenous palonosetron was well tolerated across a wide range of doses in both studies. The incidence and severity of adverse events (AEs) were similar between subjects receiving palonosetron and those receiving placebo, with no dose-dependent incidences. The most frequently reported AEs were headache, transient elevation of liver enzymes, and constipation. Systemic exposure (AUC and C(max)) for palonosetron generally increased with increasing dose. Mean total body clearance, elimination half-life, and apparent volume of distribution ranged from 1.11 to 3.90 mL/min/kg, 33.7 to 54.1 hours, and 3.85 to 12.6 L/kg, respectively, in U.S. subjects and from 2.58 to 3.50 mL/min/kg, 30.8 to 36.8 hours, and 6.96 to 9.85 L/kg, respectively, in Japanese subjects. The pharmacokinetics of palonosetron appeared to be independent of dose, with no dose adjustment required in Japanese subjects. The plasma concentration profile of palonosetron, as represented by a half-life of approximately 40 hours, may provide a clinical advantage over other 5-HT(3) antagonists.

Topics: Adult; Area Under Curve; Asian People; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Headache; Humans; Inactivation, Metabolic; Infusions, Intravenous; Injections, Intravenous; Isoquinolines; Liver; Men; Palonosetron; Quinuclidines; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Time Factors; United States

Topics: Administration, Oral; Anorexia; Antiemetics; Antineoplastic Agents; Aprepitant; Asthenia; Constipation; Diarrhea; Drug Interactions; Dyspepsia; Fatigue; Fever; Granisetron; Headache; Hiccup; Humans; Indoles; Injections, Intravenous; Isoquinolines; Morpholines; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Vomiting