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.     

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.     

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.     

Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings—a meta-analysis

Purpose

This meta-analysis was performed to evaluate the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) across different categories of chemotherapeutic emetogenicity.

Methods

A systematic review of MEDLINE (via PubMed) and OVID databases, plus major oncology conferences, identified randomized, controlled trials evaluating NK1RAs in combination with a 5-HT₃ RA plus a glucocorticoid for management of CINV. Efficacy end points were no emesis, no nausea, and complete response (CR) rates. Data were analyzed using a random effects model.

Results

Twenty-three trials (N = 11,814) were identified. Based on absolute differences (AD) for no emesis (21 %), no nausea (8 %), CR (16 %), and odd ratios (OR) of 2.62, 1.43, and 2.16, respectively, NK1RA regimens provided better CINV protection versus control groups (all p < 0.00001) in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). In patients receiving anthracycline/cyclophosphamide (AC)-based HEC, respective ADs and ORs were 14, 4, and 11 % and 1.97 (p < 0.0001), 1.17 (p = 0.04), and 1.62 (p < 0.00001). In patients receiving moderately emetogenic chemotherapy (3 trials), no statistically significant benefit of NK1RAs was found; however, positive trends were detected for CR and no emesis. NK1RAs were effective for CINV prevention in a small number of studies using high-dose chemotherapy as conditioning prior to stem cell transplant and cisplatin-based multiple-day chemotherapy (MDC).

Conclusions

This meta-analysis demonstrated the efficacy of NK1RA in preventing vomiting in patients receiving HEC (including AC), with smaller effects on prevention of nausea. Efficacy is also seen with high-dose chemotherapy and cisplatin-based MDC.

     

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.     

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.     

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.     

Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study

Purpose

A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen.

Methods

GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1–5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate—no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR?>?27 %.

Results

Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %).

Conclusion

The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin. Trial registration Clinical trial information NCT01736917

     

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.     

Measuring the impact of guideline-based antiemetic therapy on nausea and vomiting control in breast cancer patients with multiple risk factors

Purpose

The objective of this exploratory analysis was to determine if individual patient risk factors could be used to optimize chemotherapy-induced nausea and vomiting (CINV).

Methods

Through validated risk prediction models which quantify patient risk factors, 152 patients with early-stage breast cancer scheduled to received adjuvant anthracycline-based chemotherapy were categorized as being at low (level 0) or high-risk (level 1) for CINV. Prior to the first cycle of chemotherapy, low-risk patients received ondansetron and dexamethasone, while high-risk level 1 patients also received aprepitant. For subsequent cycles, patients who experienced CINV had their antiemetics changed in a stepwise manner to level 2 (extended-duration dexamethasone) or level 3 (extended-duration dexamethasone and low-dose olanzapine).

Results

The study enrolled 152 patients who received 484 cycles of chemotherapy. Forty patient cycles were classified as low risk (level 0) compared to 201, 162 and 81 that were classified as high-risk levels 1, 2 and 3, respectively. Complete control of acute and delayed vomiting was comparable and was achieved in over 85 % of patients across all risk levels (p = 0.56 and p = 0.99). In contrast, complete control of acute and delayed nausea was reduced in risk levels 1 to 3 compared to level 0 (acute = 51.2, 58.0, 45.7 vs. 70.0 %; p = 0.013)—(delayed = 32.8, 45.7, 34.6 vs. 62.5 %; p < 0.001).

Conclusions

Despite the addition of aprepitant, extended-duration dexamethasone and olanzapine, patients at high risk for CINV due to personal risk factors failed to achieve good nausea control.

     

Antiemetic efficacy and safety of a combination of palonosetron,aprepitant, and dexamethasone in patients with testicular germ cell tumor receiving 5-day cisplatin-based combination chemotherapy

Purpose

This study aimed to determine the antiemetic efficacy and safety of a combination of palonosetron, aprepitant, and dexamethasone in patients with testicular germ cell tumor (TGCT) receiving 5-day cisplatin-based combination chemotherapy.

Methods

An open-label, single-arm, multicenter study was performed in patients with TGCT who were scheduled to receive 5-day cisplatin-based combination chemotherapy. The antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2 to 5, and dexamethasone 9.9 mg on day 1 and 6.6 mg on days 2 to 8. The primary endpoint was complete response (CR) rate, which was defined as no vomiting and no rescue medication, in the overall period (0 to 216 h) in the first chemotherapy course. Incidence and severity of nausea were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) and a subjective rating scale completed by patients.

Results

Thirty patients were included in the analysis. CR was achieved in 90.0 % of the patients in the first chemotherapy course, and high CR rates were also observed in the second and third courses (82.1 and 78.3 %, respectively). The incidence of nausea peaked on days 4 to 6 in about 50 % of the patients. The reported adverse drug reactions were hiccups (13.3 %), anorexia (3.3 %), and stomach pain (3.3 %). None of these were unexpected and none were grade 3 or 4.

Conclusions

The combination antiemetic therapy examined in this study was highly effective and well-tolerated in patients with TGCT receiving 5-day cisplatin-based combination chemotherapy.     

Aprepitant for the control of delayed nausea and vomiting associated with the use of high-dose melphalan for autologous peripheral blood stem cell transplants in patients with multiple myeloma: a phase II study

Study objective

The aim of this study is to evaluate the efficacy of aprepitant as part of the antiemetic regimen for high-dose melphalan conditioning in multiple myeloma patients.

Design

This is a prospective, single-arm study.

Setting

The study was conducted at an Academic Medical Facility.

Subjects

Twenty-six patients receiving high-dose melphalan with autologous stem cell support were included in this study.

Intervention

Eligible patients were >18 years with a diagnosis of MM undergoing high-dose melphalan followed by autologous peripheral blood stem cell transplantation (PBSCT). All patients had serum aminotransferases and total bilirubin less than 2× upper limit of normal. Treatment consisted of aprepitant 125 mg orally on day 1, followed by 80 mg orally 24 and 48 h after the initial dose; ondansetron 16 mg orally day 1; dexamethasone 12 mg orally day 1, and 8 mg orally days 2–4 with breakthrough medications as needed.

Measurements and main results

Patients were evaluated for the frequency of emetic episodes, the need for breakthrough antiemetic medication, and the mean nausea score in 24-h increments beginning 24 h after chemotherapy and continuing until 120 h. Nausea score was determined using a linear analog scale (0–10). Complete response (CR) was defined as no more than one (1) emetic episode during the evaluation period. A total of 26 patients (17 male, 9 female) were enrolled in the study. Of these, 25 (96 %) were complete responders and 24 (92 %) had no documented emetic episodes during the study period. One patient (4 %) had 1 emetic episode and one patient (4 %) had 2 emetic episodes. Some degree of nausea was reported by 23/26 patients, and the mean nausea score for the entire group over the study period was 0.7 (range 0–10).

Conclusions

Addition of aprepitant to standard antiemetics resulted in low rates of delayed nausea/vomiting associated with high-dose melphalan and PBSCT, and has now become standard practice in this patient population at our institution.     

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.     

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.     

Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study

Purpose

The primary objective was to determine if a single dose of casopitant 90?mg added to ondansetron and dexamethasone would improve the control of chemotherapy-induced nausea and vomiting (CINV) over 0–120?h following initiation of oxaliplatin-based moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone.

Methods

Patients with colorectal cancer received either casopitant or placebo intravenously (IV) added to ondansetron 8?mg bid oral on study days?1 to 3 and one dose of dexamethasone 8?mg IV given prior to starting the oxaliplatin on day?1. The primary endpoint was the percentage of subjects achieving complete response (CR; no vomiting/retching or use of rescue medication) during 120?h after initiation of chemotherapy in cycle 1.

Results

No difference in the rate of CR was noted in the casopitant group compared to the placebo group for the overall (placebo 85%, casopitant 86%, p?=?0.7273), acute (placebo 96%, casopitant 97%), or delayed phases (placebo 85%, casopitant 86%). The average area under curve (0–∞) of casopitant after a single 90-mg IV dose was 8,390?ng?h/mL. At 24?h after casopitant 90-mg IV dosing, the plasma casopitant concentration was 24% lower than the values noted in prior studies with 150?mg oral administration, and the plasma exposure of the major metabolite (GSK525060) was 18% lower.

Conclusions

Addition of single-dose casopitant 90?mg IV did not improve the control of CINV at any time during 120?h following initiation of oxaliplatin-based MEC. Excellent control of CINV was achieved in this study population with the combination of ondansetron and dexamethasone alone.     

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.