The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials

In early clinical trials, the NK(1) receptor antagonist, aprepitant (EMEND(R)) was shown to improve the protection provided by the best available therapy (hereafter referred to as 'standard therapy': a 5-HT(3) receptor antagonist and dexamethasone) against chemotherapy-induced nausea and vomiting over multiple cycles of cisplatin-based chemotherapy. To further study the sustainment of antiemetic efficacy of aprepitant plus standard therapy over more than one cycle of chemotherapy, we examined combined data from the multiple cycles extensions of two phase III clinical trials of oral aprepitant plus standard therapy for the prevention of chemotherapy-induced nausea and vomiting. Data were pooled from two multicentre, randomised, double-blind, placebo-controlled studies with identical design and treatment regimens. Cancer patients receiving a first cycle of cisplatin-based (>or=70 mg/m(2)) chemotherapy were randomised to one of two treatment groups as follows: the standard therapy group received ondansetron 32 mg intravenously (i.v.) and dexamethasone 20 mg on day 1 and dexamethasone 8 mg twice daily (b.i.d.) on days 2-4. The aprepitant group received aprepitant 125 mg, ondansetron 32 mg i.v., and dexamethasone 12 mg on day 1, aprepitant 80 mg and dexamethasone 8 mg on days 2-3, and dexamethasone 8 mg on day 4. Patients had the option to receive the same blinded treatment for up to five additional cycles. The analysis used a combined exploratory endpoint of no emesis and no significant nausea (i.e. nausea which interfered with a patient's normal activities) over the 5 days following cisplatin, for up to six cycles of chemotherapy. A cumulative probabilities approach incorporating a model for transitional probabilities was used to analyse the data. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Baseline characteristics, reasons for discontinuation, and drop-out rates were similar between groups. In every cycle, the estimated probabilities (rates) of no emesis and no significant nausea were significantly higher (P<0.006) in the aprepitant group: in the first cycle, rates were 61% in the aprepitant group (N=516) and 46% in the standard therapy group (N=522), and thereafter, rates for the aprepitant regimen remained higher throughout (59% (N=89) versus 40% (N=78) for the standard therapy, by cycle 6). Repeated dosing with aprepitant over multiple cycles was generally well tolerated. Compared with patients who received standard therapy alone (a 5-HT(3) antagonist plus dexamethasone), those who received aprepitant in addition to standard therapy had consistently better antiemetic protection that was well maintained over multiple cycles of highly emetogenic chemotherapy     

枢复宁防止由非顺铂化疗所致呕吐的疗效观察

本文报道用枢复宁十地塞米松与灭吐灵十地塞米松随机对照,控制非顺铂化疗诱发的呕吐。58例病人经随机分组后,28例用枢复宁加地塞米松,30例按本院常用剂量灭吐灵加地塞米松治疗。枢复宁十地塞米松对急性恶心和呕吐的完全控制率均显著高于灭吐灵十地塞米松(分别为87％比72％,P<0.05,94％比67％,P<0.001)。对延缓性呕吐的完全控制。枢复宁十地塞米松也高于灭吐灵十地塞米松,分别为85％—94％比58％—82％(P<0.05)。枢复宁十地塞米松副作用轻,主要有头痛(13％)和便秘(9％),不引起锥体外系反应。因此,枢复宁十地塞米松是一个较为有效的联合止吐方案。     

Comparison of antiemetic efficacy of granisetron and ondansetron in Oriental patients: a randomized crossover study.

A double-blind randomized crossover trial was performed to compare the antiemetic efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the first cycle followed by the reverse order in the second cycle, or vice versa. The number of vomiting episodes and the severity of nausea in the first 24 h (acute vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied. Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and 27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes) occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each agent (P = NS). However, complete response for delayed vomiting was observed in only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P = NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten (25%) cycles respectively (P = NS). In conclusion, both granisetron and ondansetron are effective in controlling acute nausea and vomiting in Chinese patients, with equivalent antiemetic efficacy. Control of delayed nausea and vomiting is less satisfactory.     

Prevention of delayed chemotherapy-induced nausea and vomiting after moderately high to highly emetogenic chemotherapy: comparison of ondansetron, prochlorperazine, and dexamethasone

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea <1 cm on a 10-cm visual analog scale, and no administration of rescue medications, was achieved in 78% in the overall group and was not significantly different in the patients randomized to the 3 treatment arms for delayed CINV. Delayed CINV was reported by 43% to 57% of patients, with the highest incidence reported on day 3. For delayed CINV, patients receiving prochlorperazine reported the lowest average nausea score on days 2 to 5, whereas patients receiving ondansetron reported the highest nausea score (P = 0.05). No statistically significant differences in CINV or side effects of antiemetic therapy were noted between treatment groups on days 2 to 5. For patients similar to those included in this study, there does not appear to be a clinically important difference in efficacy, adverse effects, or treatment satisfaction among dexamethasone, prochlorperazine, and ondansetron in the doses used in these delayed CINV regimens on days 2 to 5 in this study.     

Ondansetron and dexamethasone in middle ear procedures

A randomised, double-blind study was conducted on 90 ASA I & II patients undergoing middle ear surgery to compare the efficacy of ondansetron, dexamethasone and a combination of Ondansett on+dexamethasone for the prevention of postoperative nausea and vomiting. Group I patients received ondansetron (0. 1 mg/kg), group IIpatients received dexamethasone(0.1z mg./Kg) while group III received ondansetron (0.1 mg./kg) + dexamethasone (0.15 mg/kg), 10 minute before induction of general anaesthesia. A standardised general anaesthetic technique was employed through out. A complete response, defined as no postoperative nausea and vomiting and no need for another rescue antiemetic during the first 4 hours after anaesthesia was achieved in 58%, 55% and 83% of patients who had received ondansetron, dexamethasone and ondansetron + dexamethasone respectively. The corresponding incidence during the next 20 hours after anaesthesia was 54%, 47% and 85%. No clinically important adverse effects were observed in any of the groups. We conclude that prophylactic therapy with ondansetron +dexamethasone,one is superior in the prevention of postoperative nausea and vomiting after middle ear surgery.     

Ondansetron versus granisetron, both combined with dexamethasone, in the prevention of cisplatin-induced emesis: Italian Group for Antiemetic Research

Background: Differences in pharmacodynamic and pharma-cokineticcharacteristics among serotonin-receptor antagonists have beenreported in preclinical studies. This prompted us to carry outa study to determine whether such differences are importantin terms of clinical efficacy or tolerability Patients and methods: 973 consecutive cancer patients scheduledto receive cisplatin for the first time (at doses > 50 mg²),entered a double-blind multicenter randomized study comparingintravenous ondansetron 8 mg versus granisetron 3 mg. Dexamethasone20 mg was added to both serotonin antagonists. On days 2 to4 after chemotherapy all patients received oral metoclopramideplus intramuscular dexamethasone as antiemetic prophylaxis fordelayed emesis. Nausea and vomiting were assessed daily untilday 6 after chemotherapy Results: We evaluated 966 patients (483 receiving ondansetronand 483 granisetron). Complete protection from acute vomiting/nauseawas obtained in 79.3%/72.0% of patients receiving ondansetronand in 79.9%/71.8% of those receiving granisetron. Completeprotection from delayed vomiting\nausea was obtained in 69.7%/52.9%and 70.0%/ 49.6% of patients receiving the ondansetron or granisetronregimens, respectively. Adverse effects were mild and not significantlydifferent between the two antiemetic regimens Conclusions: Ondansetron 8 mg and granisetron 3 mg, both combinedwith dexamethasone, showed similar efficacy and tolerabilityin the prevention of cisplatin-induced emesis. The choice betweenthe two regimens can be dictated by their respective purchaseprices antiemetics, cisplatin, dexamethasone, granisetron, ondansetron     

A multicentre, double-blind, randomised trial comparing ondansetron versus ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis

The aim was to compare the efficacy of ondansetron and a combination of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis over three consecutive courses of chemotherapy. Cancer patients scheduled to receive for the first time cisplatin (>50 mg/m(2)) in combination with other cytotoxic agents, were recruited in a multicentre, randomised, double-blind study and treated with ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. Twenty-four hours after the start of chemotherapy, patients were randomised to treatment either with oral ondansetron 8 mg bd plus placebo on days 2-5 (group A) or with oral ondansetron 8 mg bd plus oral dexamethasone 8 mg bd on days 2-3, and 4 mg bd on days 4 and 5 (group B). Two hundred and thirty-six cancer patients were recruited into the study. Complete protection from delayed vomiting/nausea in group A and group B was Obtained in 50/39% and in 63/42% of patients, respectively in the first course; in 55/34% and in 64/40% in the second and in 49/31% and 60/37% in the third. Logistic regression analysis reveals a statistically significant difference in incidence of emesis between the combination of ondansetron plus dexamethasone and ondansetron alone (P<0.05). The same model, however, shows no difference in incidence of nausea between the two treatment regimens. Ondansetron plus dexamethasone reduces the risk of delayed emesis following cisplatin chemotherapy as compared to ondansetron alone.     

High efficacy of a single oral dose of ondansetron 8 mg versus a metoclopramide regimen in the prevention of acute emesis induced by fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy for breast cancer

The aim of our single-center, prospective, randomized, open study was to evaluate the antiemetic efficacy and tolerability of a regimen based on a single oral dose of ondansetron 8 mg in comparison with a metoclopramide-based regimen, for prevention of acute FAC (fluorouracil, doxorubicin and cyclophosphamide) chemotherapy-induced emesis. A total of 149 chemotherapy-naive, female outpatients, under 50 years of age and with no history of alcohol consumption, scheduled to receive their first cycle of FAC chemotherapy, were included. The patients received either oral ondansetron (8 mg) or metoclopramide (1.5 mg/kg, i.v.), both combined with dexamethasone (16 mg, i.v.) and alprazolam (0.5 mg t.i.d. orally). No antiemetic prophylaxis was given for delayed emesis. Complete control of acute vomiting was obtained in 69/74 (93%) of patients receiving ondansetron, and in 49/75 (65%) of those receiving metoclopramide (p=0.00003). Complete control of acute nausea was obtained in 58% of patients receiving ondansetron and in 36% of those receiving metoclopramide (p=0.007). Complete prevention of delayed vomiting/nausea was achieved in 73%/20% and 60%/16% of patients, respectively. Sedation was more frequent in the metoclopramide arm (p=0.04). As far as we know this is the first study that supports the efficacy of a regimen based on a single oral dose of ondansetron 8 mg in the prevention of acute FAC chemotherapy-induced emesis. The ondansetron regimen was highly effective in female patients and was superior to the metoclopramide based regimen.     

Amelioration of cytotoxic-induced emesis with high-dose metoclopramide,dexamethasone and lorazepam

Summary A double-blind randomised controlled trial comparing the antiemetic effects of sublingual lorazepam combined with high-dose, short course metoclopramide (3 mg/kg) infused twice 3 h apart with or without i.v. dexamethasone is reported. Sixty patients receiving a total of 209 cycles of potentially severely emetic cytotoxic chemotherapy were randomised to receive one or other antiemetic regimen. In those receiving platinum-based chemotherapy the addition of dexamethasone was associated with an improvement in freedom from nausea (P<0.01) and freedom from vomiting (P<0.05). In the non-platinum-based chemotherapy group the addition of dexamethasone led to a reduction in the duration and severity of nausea, and duration of vomiting (P<0.05 in each case). Both antiemetic regimens were well tolerated with a low incidence of adverse effects and could be administered easily in an outpatient setting.     

Evaluation of SN-307 (ondansetron), given intravenously in the treatment of nausea and vomiting caused by anticancer drugs including cisplatin--a placebo-controlled, double-blind comparative study]

Clinical usefulness of ondansetron as an antiemetic for the treatment of nausea and vomiting induced by anticancer drugs including cisplatin (> or = 50 mg/m2) was evaluated by a multi-institutional, double-blind comparative study with placebo with inpatients with various malignancies. In this study, efficacy, safety and usefulness of single dose of ondansetron (4 mg) or placebo (physiological saline), given intravenously for initial nausea and vomiting were observed for 24 hours after treatment. Clinically, very effective or effective response was seen in 64% (16/25) of the group O (ondansetron) and 5.9% (1/17) of the group P (placebo). No clinically significant adverse effects or abnormal laboratory test values were reported in the group of O. Diarrhea (1 case) and the elevation of laboratory test values (GOT.GPT, T-bilirubin, LDH, in 3 cases) were reported in the group of P. General safety assessment was considered "safe" in 100% of both group O and group P, and there was no statistical difference between two groups. Usefulness was considered as "useful" in 64% (16/25) of group O and 6.3% (1/16) of group P, and O was significantly better than group P (p < 0.001) level. In conclusion, ondansetron provides a safe and effective antiemetic measure when employed therapeutically against nausea and vomiting induced by regimens including cisplatin.     

GRANISETRON COMPARED WITH ONDANSETRON PLUSDEXAMETHASONE IN THE PREVENTION OF NAUSEAAND VOMITING INDUCED BY A INTENSELYEMETOGE

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Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.

Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone.     

Single 8 mg Dose of Oral Ondansetron Failed to Prevent FAC Chemotherapy-Induced Acute Nausea and Vomiting

Abstract

The aim of this open, nonrandomized, monocentric study was to evaluate the efficacy of a single daily dose of 8 mg oral ondansetron in the prophylaxis of acute nausea and vomiting in chemotherapy-naive breast cancer patients receiving their first cycle of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC). Forty-five female patients were recruited, median age 42 years. The number of emetic episodes and the grade of nausea were recorded. 51 % of patients achieved complete, and 9% major control of acute emesis. 33% of patients experienced no acute nausea, and in 18% nausea was mild. Complete protection from nausea and vomiting (complete prophylaxis) was obtained in 12/45 (27%) of patients. Treatment success (no vomiting with no more than mild nausea) was achieved in 18/45 (40%) of patients. We conclude that the efficacy of a single dose of 8 mg oral ondansetron in controlling acute nausea and vomiting induced by FAC chemotherapy is not high enough to justify its use as a sole antiemetic agent in outpatients.     

Sustained-Release Metoclopramide Plus Methylprednisolone Versus Placebo Plus Methylprednisolone as Antiemetic Prophylaxis During Non-Cisplatin Chemotherapy: A randomized double-blind cross-over trial

In a randomized double-blind cross-over trial, sustained-release metoclopramide (S) plus methylpred-nisolone (M) was compared with placebo (P) plus methylprednisolone as antiemetic prophylaxis during two cycles of non-cisplatin chemotherapy. S was administered as 60 mg every 12 h commmencing on the evening before chemotherapy up to total of 300 mg metoclopramide in 2.5 days. Evaluation of nausea and vomiting was done by self-assessment schemes and visual analog scales. Fifty patients were included and 36 fulfilled both cycles. Mild nausea and vomiting were experienced by 81% and 83% in the S + M and P + M groups, respectively, while 42% and 39% showed complete control of nausea and vomiting during the first day of treatment. Moderate-dose S did not add to the antiemetic efficacy of M in non-cisplatin chemotherapeutic regimens.     

Efficacy of ondansetron against nausea and vomiting caused by dacarbazine-containing chemotherapy.

BACKGROUND AND METHODS. The antiemetic activity of ondansetron (Zofran, Glaxo Pharmaceuticals, Research Triangle Park, NC) was evaluated in 25 patients with recurrent melanoma who were treated sequentially with dacarbazine (DTIC), vinblastine, and cisplatin. The antiemetic regimen included ondansetron alone in 11 patients; ondansetron plus lorazepam (Ativan, Wyeth-Ayerst, Philadelphia, PA) in 9 patients; and ondansetron plus lorazepam plus metoclopramide (Reglan, A. H. Robins Co., Richmond, VA) in 5 patients. Twenty-one patients had no prior exposure to chemotherapy, whereas 4 patients had previously received the same chemotherapy regimen and had severe vomiting despite administration of standard antiemetics. RESULTS. The antiemetic efficacy of ondansetron was impressive. Administration of a single dose of 10 mg resulted in complete control of nausea and vomiting in 22 patients, and the remaining 3 patients had only mild vomiting. CONCLUSIONS. Ondansetron is highly effective in controlling the nausea and vomiting caused by dacarbazine.     

Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation

Summary The antiemetic activity of DAU 6215, a novel antagonist of 5-HT₃ receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1–1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.     

Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment.

BACKGROUND: We compared an aprepitant regimen with a control regimen of ondansetron + dexamethasone given for 4 days. PATIENTS AND METHODS: Patients scheduled to receive cisplatin > or =70 mg/m(2) were randomized to either the aprepitant regimen (aprepitant, ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2-3; dexamethasone on day 4) or control regimen (ondansetron + dexamethasone on days 1-4). Patients recorded vomiting, nausea and rescue therapy use. The primary end point was complete response (no vomiting and no use of rescue therapy) in the overall phase (days 1-5 post-cisplatin). RESULTS: Complete response rates were higher in the aprepitant than control group in the overall (72% versus 61%; P = 0.003), acute (day 1; 88% versus 79%; P = 0.005) and delayed phases (days 2-5; 74% versus 63%; P = 0.004), as were rates of no vomiting (overall 77% versus 62%, P < or = 0.001; acute 89% versus 81%, P = 0.004; delayed 79% versus 64%, P < or = 0.001). Rates of no rescue therapy were similar between groups. CONCLUSIONS: Compared with an antiemetic regimen in which ondansetron + dexamethasone were given for 4 days, the aprepitant regimen was superior in the acute, delayed and overall phases of chemotherapy-induced nausea and vomiting. The aprepitant regimen should be considered a new standard of antiemetic therapy for cisplatin-treated patients. www.ClinicalTrials.gov Identifier: NTC00090207.     

Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized,double-blind,placebo-controlled trial in Latin America

BACKGROUND: Aprepitant is a novel neurokinin 1 (NK(1)) antagonist that has been shown to improve control of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen of a 5-hydroxytriptamine-3 antagonist plus a corticosteroid. The authors sought to evaluate further the efficacy and tolerability of aprepitant plus standard therapy in a large clinical trial. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-groups, Phase III study. Patients with cancer who were scheduled to receive treatment with high-dose cisplatin chemotherapy were randomized to receive 1 of 2 treatment regimens; the standard therapy group received intravenous ondansetron 32 mg and oral dexamethasone 20 mg on Day 1, and oral dexamethasone 8 mg twice daily on Days 2-4. The aprepitant group received oral aprepitant 125 mg, intravenous ondansetron 32 mg, and oral dexamethasone 12 mg on Day 1; oral aprepitant 80 mg and oral dexamethasone 8 mg once daily on Days 2-3; and oral dexamethasone 8 mg on Day 4. Patients recorded episodes of emesis, use of rescue therapy, and severity of nausea in a diary. A modified intent-to-treat approach was used to analyze the efficacy data. The primary endpoint was complete response (no emesis and no rescue therapy) during the 5-day period postcisplatin. Treatment comparisons were made using logistic regression models, and reported adverse events and physical and laboratory assessments were used to assess tolerability. RESULTS: A total of 523 patients were evaluated for efficacy, and 568 patients were evaluated for safety. During the 5 days after chemotherapy, the percentages of patients who achieved a complete response were 62.7% in the aprepitant group (163 of 260 patients) versus 43.3% in the standard therapy group (114 of 263 patients; P < 0.001). For Day 1, the complete response rates were 82.8% for the aprepitant group and 68.4% for the standard therapy group (P < 0.001); for Days 2-5, the complete response rates were 67.7% in the aprepitant group and 46.8% in the standard therapy group (P < 0.001). The overall incidence of adverse events was similar between the 2 treatment groups (72.8% in the aprepitant group [206 of 283 patients] and 72.6% in the standard therapy group [207 of 285 patients]) as were rates of serious adverse events, discontinuations due to adverse events, and deaths. CONCLUSIONS: In patients with cancer who are receiving high-dose cisplatin-based chemotherapy, therapy consisting of aprepitant (125 mg on Day 1 and 80 mg on Days 2-3) plus a standard regimen of ondansetron and dexamethasone provided superior antiemetic protection compared with standard therapy alone and was generally well tolerated.     

A double-blind trial comparing antiemetic efficacy and toxicity of metoclopramide versus methylprednisolone versus domperidone in patients receiving doxorubicin chemotherapy alone or in combination with other antiblastic agents

Nausea and vomiting are reported in approximately 60% of neoplastic patients treated with doxorubicin used alone at doses greater than or equal to 50 mg/m2 or in combination with other noncisplatin antiblastic agents. In a double-blind study we compared the efficacy and tolerability of metoclopramide (MTC) versus Domperidone (DMP) versus methylprednisolone (MP) administered intravenously (i.v.) to inpatients. Forty-four patients entered the trial. The three antiemetic regimens were found equally effective. A complete protection from vomiting/nausea was obtained in 14/11 (93.3%/73.3%) of patients treated with MTC, in 15/14 (100%/93%) of those treated with MP and in 11/11 (78.6%/78.6%) of those treated with DMP. Side effects were slight and not significantly different among the three regimens. In conclusion, i.v. MTC and MP (DMP is no longer available in i.v. formulation) as single agents are an adequate treatment for prevention of nausea and vomiting induced by doxorubicin alone or in combination with other noncisplatin antiblastic agents.     

Antiemetic control with palonosetron in patients with gastrointestinal cancer receiving a fluoropyrimidine-based regimen in addition to either irinotecan or oxaliplatin: a retrospective study

Background: For moderately emetogenic chemotherapy, palonosetron (PALO) is reported to provide complete control of chemotherapy-induced nausea and vomiting (CINV) in 69% of patients. Prior to August 2009, our gastrointestinal (GI) cancer patients receiving the moderately emetogenic compounds oxaliplatin or irinotecan plus a fluoropyrimidine regimen received ondansetron and dexamethasone orally on day 1 of chemotherapy for CINV prevention. Beginning in August of 2009, ondansetron was replaced by PALO 0.25 mg (intravenous push). Methods: This is a single-institution retrospective study of GI cancer patients who received oxaliplatin or irinotecan plus a fluoropyrimidine. Failure of an antiemetic regimen was defined as grade ≥1 vomiting or grade ≥2 nausea (Common Terminology Criteria for Adverse Events, version 3) on days 1 through 5 following chemotherapy. Patients were divided for analysis into pre-PALO and post-PALO cohorts. Fisher's exact test compared cohort differences. Results: A total of 305 patients were included in the study, with 157 patients in the pre-PALO cohort and 148 in the post-PALO cohort. For all patients, the risk of antiemetic failure was reduced from 50.3% [95% confidence interval (CI) 42.2-58.4%] to 28.4% (95% CI 21.3-36.4%) with PALO. This reduction in the relative risk of antiemetic failure was observed in all subgroups. Conclusion: The addition of PALO may provide increased control of CINV for the moderately emetogenic regimens of oxaliplatin or irinotecan plus a fluoropyrimidine in GI cancer patients.