Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial

Purpose

A phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens.

Methods

This multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25?mg intravenously) and dexamethasone (8?mg intravenously) before chemotherapy, while the other was administered the same regimen on day?1 followed by dexamethasone 8?mg orally on days?2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days?1?C5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint.

Results

Of 332 chemotherapy-na?ve patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day?1 (n?=?166), and 71.1% for those also administered dexamethasone on days?2 and 3 (n?=?166; difference ?3.6% (95% confidence interval, ?13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0?C24?h post-chemotherapy; 88.6% versus 84.3%; P?=?0.262) and delayed phases (days?2?C5; 68.7% versus 77.7%; P?=?0.116).

Conclusions

Palonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3?days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens.     

Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial

Background

Palonosetron (Aloxi®, Onicit®) is a pharmacologically unique 5-HT₃ receptor antagonist (RA) approved as a single IV injection for the prevention of nausea and vomiting induced by chemotherapy (CINV) of either moderate or highly emetogenic potential (MEC and HEC, respectively). An oral palonosetron formulation has been developed and compared to the IV formulation.

Methods

In this multinational, multicenter, double-blind, double-dummy, dose-ranging trial, 651 patients were randomly assigned to receive one of the following as a single dose prior to moderately emetogenic chemotherapy: oral palonosetron 0.25, 0.50, and 0.75 mg or IV palonosetron 0.25 mg. Patients were also randomized (1:1) to receive dexamethasone 8 mg IV or matched placebo on day 1. The primary endpoint was complete response (CR; no emesis, no rescue therapy) during the acute phase (0–24 h).

Results

Acute CR rates were 73.5, 76.3, 74.1, and 70.4 % for all patients receiving the palonosetron 0.25, 0.50, and 0.75 mg oral doses, and for IV palonosetron 0.25 mg, respectively; delayed CR (24–120 h) rates were 59.4, 62.5, 60.1, and 65.4 %, and overall CR (0–120 h) rates were 53.5, 58.8, 53.2, and 59.3 %, respectively. The addition of dexamethasone improved emetic control (acute CR rate) by at least 15 % for all groups except oral palonosetron 0.25 mg, where the acute CR improvement was approximately 7 %. Adverse events were similar in nature, incidence, and intensity for all oral and IV palonosetron groups, and were the expected adverse events for 5-HT₃ RAs (primarily headache and constipation).

Conclusion

Oral palonosetron has a similar efficacy and safety profile as IV palonosetron 0.25 mg and may be the preferred formulation in certain clinical situations. Among the tested oral treatments, a palonosetron 0.50-mg oral dose has been favored for the prevention of CINV in patients receiving moderately emetogenic chemotherapy due to a numerical gain in efficacy without a side effect disadvantage.     

Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL)

Purpose

The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT₃) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids.

Methods

Patients received a single intravenous bolus of palonosetron (0.25?mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0?C120?h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint.

Results

Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0?C24?h) and delayed (24?C120?h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%.

Conclusions

This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin??s lymphoma receiving MEC regimen containing steroids.     

Cost-effectiveness analysis of aprepitant in the prevention of chemotherapy-induced nausea and vomiting in Belgium

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer chemotherapy which may increase morbidity, reduce quality of life and threaten the success of cancer therapy. Aprepitant is effective in preventing CINV, achieving higher complete response (no emesis and no rescue therapy) compared to standard prevention, in patients receiving either highly (HEC) or moderately emetogenic chemotherapy (MEC; absolute reduction = 11 and 13%, respectively). We assessed the cost effectiveness of aprepitant-based vs standard prevention in these indications in Belgium. MATERIALS AND METHODS: A decision analytical model was developed in MS Excel (Fig. 1). To estimate resource use, two approaches were used. The first is based on the preventive regimens applied in randomized controlled trials comparing aprepitant-based CINV prevention (for HEC: aprepitant days 1-3, ondansetron 32 mg i.v. day 1, oral placebo twice daily days 2-4, oral dexamethasone days 1-4; for MEC: aprepitant days 1-3, ondansetron 16 mg p.o. day 1, placebo on days 2-3, oral dexamethasone day 1), vs a standard regimen (for HEC: oral placebo days 1-3, ondansetron 32 mg i.v. day 1 and 16 mg p.o. days 2-4, oral dexamethasone days 1-4; for MEC: oral placebo, ondansetron 16 mg p.o. days 1-3, dexamethasone day 1) The second analysis is based on current real-world resource use in the Belgian setting in the prevention of CINV using a longitudinal Hospital Database. CINV-specific utility values were used to calculate quality-adjusted life years (QALYs). Drug costs were obtained from official reimbursement listings. Treatment costs for CINV were obtained from a German study and adapted to Belgium. RESULTS: The aprepitant-based regimen is associated with 0.003 and 0.014 more QALYs in HEC and MEC, respectively and with per patient savings of 66.84 (trial based) and 74.62 (real-life based) for HEC and 17.95 (trial based) and 21.70 (real-life based) for MEC. Hence, aprepitant is both more effective and less expensive (=dominant). One-way sensitivity analyses were performed on treatment cost of emesis, the clinical benefit of aprepitant and the cost of ondansetron and showed that the results were robust on the first two parameters but sensitive on the decrease in cost of ondansetron for the moderately emetogenic chemotherapy regimens. CONCLUSIONS: In both approaches, the aprepitant-based strategy is more effective and less expensive compared to standard care.     

Safety and efficacy of aprepitant,ramosetron, and dexamethasone for chemotherapy-induced nausea and vomiting in patients with ovarian cancer treated with paclitaxel/carboplatin

Purpose

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.

Methods

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).

Results

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.

Conclusions

The combination of aprepitant, ramosetron, and high-dose dexamethasone demonstrated efficacy for CINV prevention in ovarian cancer patients receiving paclitaxel and carboplatin.     

Impact of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of ondansetron and dexamethasone

Introduction  Pharmacokinetic interactions between casopitant (a substrate and weak to moderate inhibitor of CYP3A), dexamethasone (a substrate and weak inducer of CYP3A), and ondansetron (a mixed CYP substrate) were evaluated in a two-part, three-period, single-sequence study in two groups of healthy subjects. Materials and methods  Part 1: subjects received oral casopitant (regimen A); oral dexamethasone and IV ondansetron (regimen B); and oral casopitant, a reduced dose of oral dexamethasone, and IV ondansetron (regimen C). Part 2: subjects received oral casopitant (regimen D); IV dexamethasone and oral ondansetron (regimen E); and oral casopitant, IV dexamethasone, and oral ondansetron (regimen F). Each regimen was separated by 14 days. Results  Casopitant AUC in regimen C was increased 28% on day 1 but decreased 34% on day 3 compared to casopitant alone in regimen A. When given with casopitant and ondansetron in regimen C, dexamethasone AUC was 17% lower on day 1, but similar on day 3, compared to regimen B (representing dose-normalized increases in exposure of 39% and 108%, respectively). Ondansetron exposure was equivalent in regimens B and C. Casopitant AUC in regimen F was similar to regimen D on days 1 and 3. Dexamethasone AUC increased 21% when given with oral casopitant and oral ondansetron (regimen F compared to regimen E). Ondansetron exposure was equivalent in regimens E and F. Conclusion  When repeat-dose oral dexamethasone is to be coadministered with oral casopitant, a reduction in dexamethasone dose may be considered; however, no change in casopitant dose is required. Ondansetron exposure was not affected by coadministration with casopitant. Presented as an invited lecture at the Supportive Care in Cancer MASCC/ISOO 2008 International Symposium in Houston, Texas on June 26–28, 2008. This work was sponsored by GlaxoSmithKline. C Lates and R Blum received funding from GlaxoSmithKline to conduct this study. All other authors were employees of GlaxoSmithKline.     

Adherence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice

Purpose

A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients’ quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)’s usual practice demonstrates a high incidence (45 %) of CINV, despite premedication with short-acting 5-HT₃-serotonin-receptor antagonists (5-HT₃-RAs). National Comprehensive Cancer Network (NCCN)’s evidence-based guidelines recommend the combination of the long-acting 5-HT₃-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58 %) to antiemetic guidelines may have explained our high CINV incidence.

Methods

One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL.

Results

Adherence to ordering MEC guideline antiemetics increased significantly, from 58 % to a sustained 90 %, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84 % of patients, respectively, did not experience CINV. There was no significant change in QOL.

Conclusion

Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas.     

A phase III open-label study to assess safety and efficacy of palonosetron for preventing chemotherapy-induced nausea and vomiting (CINV) in repeated cycles of emetogenic chemotherapy

Purpose

Prevention of chemotherapy-induced nausea and vomiting (CINV) is of great importance for the completion of multiple cycles of cancer chemotherapy. Palonosetron is a second-generation 5-HT₃ receptor antagonist with proven efficacy for both acute and delayed CINV. This study was designed to assess the safety and efficacy of 0.75?mg palonosetron in repeated cycles of highly emetogenic chemotherapy or anthracycline–cyclophosphamide combination (AC/EC).

Methods

We gave 0.75?mg palonosetron to 538 patients 30?min prior to ≥50?mg/m² cisplatin or AC/EC on day?1. Prophylactic dexamethasone was administered on days?1–3. The primary endpoint was the incidence rate of adverse events (AEs). The secondary endpoint was complete response rate (CR, defined as no emesis and no rescue medication) throughout the study period.

Results

Treatment-related AEs were seen in 44% (237 of 538 patients). Serious AEs were seen in 4% (23 of 538 patients), all considered unrelated or unlikely to be related to palonosetron. Only one patient discontinued the study due to a treatment-related AE. No trend toward worsening of AEs was observed in subsequent cycles of chemotherapy. Complete response rates were maintained throughout repeated cycles.

Conclusion

The extraordinary safety profile and maintenance of efficacy of 0.75?mg palonosetron combined with dexamethasone were demonstrated throughout repeated chemotherapy cycles.     

Casopitant improves the quality of life in patients receiving highly emetogenic chemotherapy

Purpose  

The control of chemotherapy-induced nausea and vomiting (CINV) is critical in preventing poor health outcomes and increasing patient quality of life. The objective of this study was to evaluate the impact of the addition of casopitant to dual-combination therapy of dexamethasone and ondansetron on quality of life in patients receiving highly emetogenic chemotherapy (HEC).     

The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy

Purpose

Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.

Methods

A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥?70 mg/m² or doxorubicin, ≥?50 mg/m² and cyclophosphamide, ≥?600 mg/m²), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2–4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38–79; 43 % women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.

Results

During the 72-h observation period, 39 out of 56 (70 %) patients receiving olanzapine had no emesis compared to 16 out of 52 (31 %) patients with no emesis for patients receiving metoclopramide (p?<?0.01). Patients without nausea (0, scale 0–10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68 % (38 of 56), and metoclopramide, 23 % (12 of 52) (p?<?0.01). There were no grade 3 or 4 toxicities.

Conclusions

Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.     

Antiemetic efficacy of single-dose palonosetron and dexamethasone in patients receiving multiple cycles of multiple day-based chemotherapy

Introduction

The goal of pharmacological prophylaxis of chemotherapy-induced nausea and vomiting (CINV) should be the elimination of both nausea and vomiting symptoms during all planned chemotherapy cycles. The aim of this study was to assess the efficacy of a single dose of palonosetron and dexamethasone to prevent CINV and to guarantee an adequate food intake (FI) in patients receiving several cycles of multiple day-based chemotherapy (MD-CT).

Methods

Patients with advanced cancer but without a compromised nutritional status (bone mass index?≥?18.5) were treated with 0.25?mg palonosetron plus 20?mg dexamethasone before MD-CT. The MD-CT regimen was either epirubicin plus ifosfamide or paclitaxel plus cisplatin and ifosfamide. Nausea, vomiting, and FI were monitored in a 7-day diary. Complete response (CR: no vomiting and no rescue therapy) was the primary endpoint, while complete control (CC: CR and no more than mild nausea) and the evaluation of FI were secondary endpoints. The endpoints were evaluated during the overall timescale (0–168?h) of the chemotherapy regimen.

Results

Fifty patients were enrolled, 80% of whom achieved CR and 78% achieved CC. During the six chemotherapy cycles, CR and CC ranged from 76% to 88% and from 62% to 88%, respectively. Moreover, patients with CR had a significantly (p?<?0.0001) higher weekly food intake compared with patients not achieving CR.

Conclusions

This trial was the first to assess the efficacy of palonosetron and dexamethasone for the prevention of both nausea and vomiting in patients receiving multiple cycles of MD-CT. In this trial, the ability of patients to intake an adequate amount of food each week was correlated with nausea, thus providing clinicians with an objective parameter for the measurement of the effects of nausea. A single dose of palonosetron and dexamethasone was able to prevent CINV in most patients receiving 3?days of chemotherapy during all planned chemotherapy cycles.     

Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV)

Purpose

Preventing chemotherapy-induced nausea and vomiting (CINV) is integral to treatment success in patients with cancer. This analysis was undertaken to assess the relative efficacy and safety of palonosetron versus older 5HT₃ RAs in preventing CINV associated with moderately or highly emetogenic chemotherapy.

Methods

Patient-level data from four randomized, double-blind, phase III trials comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg were analyzed. Endpoints included complete response (CR: no emesis and no rescue antiemetics) in the acute (0–24 h), delayed (>24–120 h), and overall (0–120 h) postchemotherapy periods (primary), complete control (CC: no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic episodes, and nausea severity.

Results

CR rates were significantly higher for palonosetron (n?=?1,787) versus older 5HT₃ RAs (n?=?1,175) in the delayed (57 vs 45 %, P?<?0.0001) and overall periods (51 vs 40 %, P?<?0.0001); odds ratios (95 % CI) in the acute, delayed, and overall periods were 1.15 (0.98–1.34), 1.62 (1.40–1.88), and 1.56 (1.34–1.81), respectively. Significant differences in CC rates and nausea severity were observed for the delayed and overall periods and in emetic episodes for all three periods. The incidence of treatment-related adverse events was similar with palonosetron (0.25 mg, 20.0 %; 0.75 mg, 26.5 %) and older 5HT₃ RAs (27.5 %).

Conclusions

Palonosetron is more effective than older 5HT₃ RAs for controlling CINV in the delayed and overall postchemotherapy periods.     

Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting following high-dose cisplatin in Chinese patients: a randomized,double-blind,placebo-controlled phase III trial

Purpose

Aprepitant, an oral neurokinin-1 receptor antagonist, has demonstrated improved control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of aprepitant in patients receiving highly emetogenic chemotherapy (HEC) in Asian countries.

Methods

This multicenter, double-blind, placebo-controlled trial assessed the prevention of CINV during the acute phase (AP), delayed phase (DP), and overall phase (OP). Patients receiving HEC were randomized to either an aprepitant group (day 1, aprepitant 125 mg; days 2–3, aprepitant 80 mg) or a standard therapy group (days 1–3, placebo). Both groups received intravenous granisetron and oral dexamethasone. The primary end point was complete response (CR; no emesis and no use of rescue therapy) during the OP.

Results

Of the 421 randomized patients, 411 (98 %) were assessable for efficacy; 69.6 % (142/204) and 57.0 % (118/207) of patients reported CR during the OP in the aprepitant and standard therapy groups, respectively (P?=?0.007). CR rates in the aprepitant group were higher during the DP (74.0 % vs. 59.4 %, P?=?0.001) but were similar during the AP (79.4 % vs. 79.3 %, P?=?0.942). Toxicity and adverse events were comparable in both groups.

Conclusions

The addition of aprepitant to standard antiemetic treatment regimens for Chinese patients undergoing HEC provided superior CINV prevention and was well tolerated.     

Efficacy and safety of triple therapy with aprepitant,palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy for gynecological cancer: KCOG-G1003 phase II trial

Purpose

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/m²).

Methods

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).

Results

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).

Conclusions

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.     

Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review

Purpose

Newer drugs incorporated in prophylactic regimens for chemotherapy-induced nausea and vomiting (CINV) have resulted in significantly reduced rates of this feared complication of cytotoxic chemotherapy. However, both delayed chemotherapy-induced nausea and breakthrough CINV remain difficult areas of management and require novel treatment strategies. Recent randomized trial evidence has suggested that olanzapine, an atypical antipsychotic, may have a role in both the prevention and treatment of CINV. A systematic review was conducted to assess the efficacy of olanzapine in (a) preventing CINV in highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) and (b) the treatment of breakthrough CINV. The toxicity of olanzapine in this setting was also reviewed.

Methods

MEDLINE, Embase and Cochrane Database of Systematic Reviews databases were searched to identify all randomized clinical trials (RCTs) investigating olanzapine in patients receiving chemotherapy.

Results

A total of 488 patients from three trials of CINV prophylaxis and 323 patients from three trials of breakthrough CINV were included. Regimens including olanzapine were associated with significant improvements in CINV prevention with both HEC and MEC. Single agent olanzapine for breakthrough nausea was superior to standard alternative options.

Conclusion

Data from RCTs support the use of an olanzapine containing combination regimen as an option for CINV prophylaxis and single agent olanzapine for the treatment of breakthrough CINV. In the included trials, the short duration of olanzapine appears safe and well tolerated.     

The efficacy of triplet antiemetic therapy with 0.75 mg of palonosetron for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy

Background

Chemotherapy-induced nausea and vomiting (CINV) are some of the most problematic symptoms for cancer patients. Triplet therapy consisting of a 5HT3 receptor antagonist, aprepitant, and dexamethasone is a guideline-recommended antiemetic prophylaxis for highly emetogenic chemotherapy (HEC). The efficacy and safety of triplet therapy using a 0.75-mg dose of palonosetron have not yet been investigated. We performed a prospective phase II study using triplet antiemetic therapy with 0.75 mg of palonosetron.

Methods

Chemotherapy-naïve lung cancer patients scheduled to receive HEC were enrolled. The eligible patients were pretreated with antiemetic therapy consisting of the intravenous administration of 0.75 mg of palonosetron, and 9.9 mg of dexamethasone and the oral administration of 125 mg of aprepitant on day 1, followed by the oral administration of 80 mg of aprepitant on days 2–3 and the oral administration of 8 mg of dexamethasone on days 2–4. The primary endpoint was the complete response rate (the CR rate; no vomiting and no rescue medication) during the overall phase (0–120 h).

Results

The efficacy analysis was performed in 63 patients. The CR rates during the overall, acute and delayed phases were 81.0, 96.8, and 81.0 %, respectively. The no nausea and no significant nausea rate during the overall phase were 54.0 and 66.7 %, respectively. The most common adverse event was grade 1 or 2 constipation.

Conclusions

Triplet antiemetic therapy using a 0.75-mg dose of palonosetron shows a promising antiemetic effect in preventing CINV in lung cancer patients receiving HEC.     

Efficacy and safety of palonosetron as salvage treatment in the prevention of chemotherapy-induced nausea and vomiting in patients receiving low emetogenic chemotherapy (LEC)

Purpose

The purpose of this study is to evaluate the efficacy and safety of intravenous (IV) palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who had incomplete control of CINV during their previous cycle of low emetogenic chemotherapy (LEC).

Methods

Patients with histologically or cytologically confirmed cancer, ≥18 years of age, with a Karnofsky Performance Scale score of ≥50 % who had received LEC that induced vomiting and/or at least moderate nausea during their previous treatment cycle received palonosetron 0.25 mg IV 30 min before chemotherapy. Outcomes were recorded in patient diaries over 120 h and at an end-of-study visit on days 6, 7, or 8 after LEC administration. The primary efficacy variable was the complete response rate, defined as no emetic episodes and no rescue medication at 0–24 h (acute post-chemotherapy phase), 24–120 h (delayed phase), and 0–120 h (overall).

Results

Complete responses among the intent-to-treat study population (n?=?34) were recorded for 88.2 % of patients in the acute phase, 67.6 % in the delayed phase, and 67.6 % overall. No emetic episodes occurred in 91.2 and 79.4 % of patients during the acute and delayed phases, respectively, and no nausea in 73.5 and 52.9 %, respectively. Palonosetron was well tolerated; only two patients experienced treatment-related adverse events.

Conclusions

Among the patients with cancer who had a history of CINV with LEC, palonosetron was effective in preventing CINV in both the acute and delayed post-chemotherapy phases, and was well tolerated. Randomized comparative studies in larger populations of patients receiving LEC are needed to confirm these findings.     

Palonosetron plus 3-day aprepitant and dexamethasone to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy

Background

The combination of a neurokinin-1 receptor antagonist, dexamethasone, and a 5-HT₃ receptor antagonist is currently the standard antiemetic treatment in patients receiving cisplatin-based high emetogenic chemotherapy (HEC). The aim of this study was to evaluate the efficacy of a combination of palonosetron, a unique second-generation 5-HT₃ receptor antagonist, aprepitant, the only approved neurokinin-1 receptor antagonist, and dexamethasone as antiemetic prophylaxis in patients receiving HEC (cisplatin ??50?mg/mq).

Methods

Chemotherapy-na?ve adult patients, receiving cisplatin-based HEC, were treated with palonosetron 0.25?mg/i.v., dexamethasone 20?mg/i.v., and aprepitant 125?mg/p.o., 1-h before chemotherapy. Aprepitant 80?mg/p.o. and dexamethasone 4?mg p.o. were administered on days 2?C3. Primary end point was complete response (CR; no vomiting and no use of rescue medication), during the overall study period (0?C120?h). Secondary end points were complete control (CR and no more than mild nausea), emesis-free rate, and nausea-free rate during the acute (0?C24?h), delayed (24?C120?h), and overall (0-120?h) periods. Safety was also evaluated.

Results

A total of 222 patients were included in the study. Median age was 62?years, 76.6% were male and 23.4% female, and most common tumors were lung (66.7%) and head and neck (15.8%); 70.3% of patients achieved CR during the overall study period. Complete control, emesis-free rate, and nausea-free rate were 70.3%, 92.8%, and 59.9%, respectively, during the overall phase. The most commonly reported side effects were constipation (39% of patients) and headache (5%).

Conclusions

This study shows that palonosetron in combination with aprepitant and dexamethasone is effective to prevent chemotherapy-induced nausea and vomiting in patients treated with cisplatin-based HEC.     

Should clinicians always administer dexamethasone beyond 24 h after chemotherapy to control delayed nausea and vomiting caused by moderately emetogenic regimens? Insight from the re-evaluation of two randomized studies

Purpose

Data from two noninferiority trials of a dexamethasone-sparing regimen were assessed for the impact of acute nausea and vomiting on delayed outcome in patients undergoing moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC).

Methods

Chemo-naive patients were randomized to receive palonosetron (0.25 mg IV) plus dexamethasone (8 mg IV) on day 1 of chemotherapy, or the same regimen followed by oral dexamethasone on days 2 and 3 in the MEC (n?=?237) and AC (n?=?380) cohorts. Patients were divided into two groups according to whether or not they experienced vomiting and/or moderate-to-severe nausea during the acute phase (high- and low-risk groups, respectively). Primary efficacy endpoint was the complete protection (CP) against delayed vomiting and moderate-to-severe nausea. Patient’s satisfaction (0–100 mm visual analog scale) was also analyzed.

Results

Among the 209 low-risk patients undergoing MEC, delayed CP occurred in 82.9 % of those who received single-dose dexamethasone and 89.8 % of those who received 3-day dexamethasone (P?=?0.165). Of the 271 low-risk patients undergoing AC, CP was achieved in 71.7 % of those treated with single-dose dexamethasone and 84.2 % treated with 3-day dexamethasone (P?=?0.019). In spite of these observations, the patient satisfaction data was not influenced by dexamethasone regimen. In both cohorts, occurrence of acute vomiting or moderate-to-severe nausea was the key independent-predictor for delayed vomiting or nausea, respectively.

Conclusions

The dexamethasone-sparing regimen provides adequate delayed protection in patients undergoing MEC who are at low risk for delayed symptoms, and can still be discussed for low-risk AC patients as the daily difference in control is modest. Additional dexamethasone doses can be customized on the basis of occurrence or absence of acute symptoms in the first cycle of MEC and even AC.