A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A Hoosier Oncology Group study

In a previous phase I study, olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of chemotherapy-induced nausea and vomiting in chemotherapy-naïve patients. The regimen was 5 mg/day of oral olanzapine on the 2 days prior to chemotherapy, 10 mg on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg and dexamethasone 20 mg), and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25–84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2–5 postchemotherapy), and 80% for the overall period (0–120 h postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin 70 mg/m²). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin 50 mg/m²). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea [0 on scale of 0–10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or restlessness experienced by the patients. Complete response and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Olanzapine is safe and highly effective in controlling acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly and moderately emetogenic chemotherapy.     

Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy

Purpose

Chemotherapy-induced nausea and vomiting includes both Acute (0–24 h) and Delayed (24–120 h) components with different physiologic mechanisms. A combination of a serotonin antagonist, a corticosteroid, and an NK-1 antagonist has proven effective against this problem. However, standard antiemetic regimens require administration over 3–4 days after chemotherapy. The present study evaluated a more convenient single-day three-drug antiemetic regimen for patients receiving moderately emetogenic chemotherapy.

Materials and methods

Chemotherapy-naïve patients with solid tumors receiving cyclophosphamide and/or doxorubicin were eligible. Patients could not have pre-existing etiologies for vomiting. Prior to chemotherapy, patients received a single dose of aprepitant 285 mg p.o., dexamethasone 20 mg p.o., and palonosetron 0.25 mg i.v. A daily patient diary recording episodes of emesis and severity of nausea was then kept for 5 days. Any further antiemetics were considered rescue medication.

Results

Forty-one eligible and evaluable patients (40 women, one man) with breast cancer were entered on study. Most were receiving adjuvant chemotherapy. Complete Response (no vomiting, no rescue medication) was seen in 51% of patients, including 76% with Complete Response for the Acute period and 66% for the Delayed period. No emesis was reported for 100% of patients in the Acute period and 95% in the Delayed period. No Nausea was seen in 32% of patients. No untoward toxicities were seen.

Conclusion

A single-day three-drug antiemetic regimen is feasible and effective for protection against both Acute and Delayed vomiting after moderately emetogenic chemotherapy. Formal comparison to a standard multi-day antiemetic regimen is warranted.     

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.     

Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea

 There is still controversy as to what constitutes the optimal therapy for acute and delayed chemotherapy-induced emesis and nausea. We conducted a three-armed randomized multi-centre study in 193 chemotherapy-naive patients receiving highly emetogenic chemotherapy inducing both acute and delayed symptoms (cisplatin ≥50 mg/m², carboplatin ≥300 mg/m², cyclophosphamide ≥750 mg/m², ifosfamide ≥1.5 g/m² on day 1). Group A: 1×5 mg tropisetron i.v. on day 1+2, then 10 mg p.o. (oral dose now recommended: 5 mg); group B: tropisetron as for A+dexamethasone, 20 mg i.v., on days 1+2, then 4 mg i.v./p.o.; group C: tropisetron as for A+metoclopramide, 20 mg i.v.+2×10 mg p.o. on day 1, then 3×10 mg p.o. Treatment was continued for at least 2 days after the end of chemotherapy. Tropisetron+dexamethasone was significantly superior to tropisetron alone both for acute (P=0.0064) and delayed (P=0.0053) emesis. Complete control of acute and delayed emesis (nausea) was achieved in 80% (75%) and 53% (46%) in group A, 97% (90%) and 80% (58%) in group B, and 86% (80%) and 49% (45%) in group C. Patients completely asymptomatic during the whole cycle accounted for 26% of those in group A, 49% in group B and 28% in group C. The most frequent adverse events were constipation (16.6%), headache (7.3%) and tiredness (7.3%). Once-daily tropisetron+dexamethasone over several days is well tolerated and is a simple means of achieving further significant improvement in the efficacy of tropisetron against acute and delayed symptoms.     

Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer

GOALS OF WORK: The aims of this study were to assess the safety and antiemetic efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ cell tumors. MATERIALS AND METHODS: Forty-one men undergoing 5-day cisplatin-based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days. Efficacy endpoints included emesis, intensity of nausea and its interference with patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was studied for electrocardiograph effects and pharmacokinetic evaluation. MAIN RESULTS: This multiple-day antiemetic regimen was safe, with headache and constipation the most common treatment-related adverse events, mostly mild. Neither adverse events nor electrocardiographic changes appeared to increase in frequency, duration, or intensity over time despite a 1.42-fold systemic accumulation of palonosetron with repeated doses. The majority of patients had no emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate-to-severe nausea, and did not require rescue medication. Most patients reported that nausea had no significant effect on daily functioning on days 1-4 (72%) and days 5-9 (85%). CONCLUSIONS: Palonosetron on days 1, 3, and 5, along with a regimen of dexamethasone, was safe and well tolerated and effectively controlled both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy for testicular cancer.     

Randomized study of dexamethasone treatment for delayed emesis, anorexia and fatigue induced by irinotecan

The prevention of post-chemotherapy symptoms such as delayed emesis, anorexia, and fatigue induced by irinotecan has not been studied. We compared the effects of dexamethasone (Dex) with those of a placebo on these symptoms in a randomized study. Seventy patients scheduled to receive irinotecan chemotherapy were enrolled in the study and randomly divided into a treatment or a placebo group. In the treatment group, 8 mg of Dex were administered on days 2–4 after the start of chemotherapy. All patients in both groups received Dex and granisetron for prophylaxis against acute emesis on day 1. We evaluated 68 patients (35 receiving Dex, 33 receiving the placebo). Although delayed emesis was completely prevented in most of patients in both groups (Dex, 82.9%; placebo, 78.8%), anorexia and fatigue were more completely prevented in those in the Dex group (Dex, 62.9% and 77.1%, placebo, 39.4% and 57.6%, respectively). The effect of Dex on improving simultaneous prophylaxis against all three symptoms was almost significant (Dex, 60.0%; placebo, 36.4%; P=0.058). The safety profiles of the two groups were not discernibly different. These results suggest that treatment with Dex may be beneficial to reduce post-chemotherapy symptoms induced by irinotecan, specifically anorexia and fatigue, with acceptable toxicities.Supported in part by Grants-in-aid for Cancer Research from the Ministry of Health and Welfare and from the Second-term Comprehensive 10-year Strategy for Cancer Control.     

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study

Purpose  

Chemotherapy-induced nausea and vomiting (CINV) is a side effect related to administration of the adjuvant temozolomide (TMZ) in patients affected by glioblastoma. After chemoradiotherapy, adjuvant TMZ is administered as an oral multiple-day regimen, and TMZ-associated CINV may interfere with the continuation of chemotherapy, with potentially negative consequences on clinical efficacy. The aim of the present study was to investigate the efficacy of palonosetron for prevention of CINV-induced by adjuvant TMZ.     

Aprepitant, dexamethasone, and palonosetron in the prevention of doxorubicin/cyclophosphamide-induced nausea and vomiting

Purpose  

This study evaluated the efficacy and tolerability of aprepitant, dexamethasone, and palonosetron in the prevention of nausea and vomiting in breast cancer patients receiving their initial cycle of doxorubicin and cyclophosphamide (AC).     

Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy

This paper uses an evidence-based approach whenever possible to formulate recommendations, emphasizing the results of controlled trials concerning the best use of antiemetic agents. We address issues of dose, schedule, and route of administration of five selective 5-HT₃ antagonists. We conclude that for each of these five drugs, there is a plateau in therapeutic efficacy above which further dose escalation does not improve outcome. Furthermore, for all classes of antiemetic agents, a single dose is as effective as multiple doses or a continuous infusion. The oral route is as efficacious as the intravenous route of administration, even with chemotherapy of high emetic risk. Selective antagonists of the type 3 serotonin receptor (5-HT₃) in combination with dexamethasone and aprepitant are the standard of care for the prevention of emesis following chemotherapy of high emetic risk.An erratum to this article can be found at     

The efficacy and safety of palonosetron compared with granisetron in preventing highly emetogenic chemotherapy-induced vomiting in the Chinese cancer patients: a phase II, multicenter, randomized, double-blind, parallel, comparative clinical trial

PURPOSE: This clinical trial was conducted to evaluate the efficacy and safety of Palonosetron in preventing chemotherapy-induced vomiting (CIV) among the Chinese cancer patients. PATIENTS AND METHODS: Two hundred and forty patients were scheduled to be enrolled and randomized to receive a single intravenous dose of palonosetron 0.25 mg, or granisetron 3 mg, 30 min before receiving highly emetogenic chemotherapy. The primary efficacy endpoint was the complete response (CR) rate for acute CIV (during the 0-24-h interval after chemotherapy). Secondary endpoints included the CR rates for delayed CIV (more than 24 h after chemotherapy). RESULTS: Two hundred and eight patients were accrued and received study medication. CR rates for acute CIV were 82.69% for palonosetron and 72.12% for granisetron, which demonstrated that palonosetron was not inferior to granisetron in preventing acute CIV. Comparisons of CR rates for delayed CIV yielded no statistical difference between palonosetron and granisetron groups and did not reveal non-inferiority of palonosetron to granisetron. Adverse events were mostly mild to moderate, with quite low rates among the two groups. CONCLUSIONS: A single dose (0.25 mg) of palonosetron is not inferior to a single dose (3 mg) of granisetron in preventing CIV and possesses an acceptable safety profile in the Chinese population.     

A review of patient self-report tools for chemotherapy-induced nausea and vomiting

Goals of work  The assessment of chemotherapy-induced nausea, vomiting and retching (CINVR) is important and to date no review has comprehensively assessed available patient self-report tools. The aim was to undertake a review of their utility, content and psychometric properties. Materials and methods  One thousand three hundred and forty-seven citations were identified by electronic and hand searches resulting in 24 non-duplicate abstracts, 15 articles for analysis, and six articles, which fitted the inclusion criteria. E-mail investigations discovered a further scale, resulting in seven measures. Results  The review highlighted the strengths and weaknesses of current tools. The multiple domains, phases and aspects of CINVR signify that the assessment tools varied markedly. The diverse requirements of research and clinicians also contribute to the variation. There was a notable disparity in the quality of scales and paucity in terms of their development and psychometric evaluation. We found that several self-assessment scales currently perceived as well-validated tools have problems in terms of their validity, reliability and appropriateness. Conclusions  The constituents of a scale relevant for both clinical and research use were assessed and it was recommended that a modular tool focusing on two domains (nausea and vomiting); two phases (acute and delayed); measuring the aspects of occurrence, frequency, intensity alongside duration and functional interference; and antiemetic use and adverse events should be developed. Based on these recommendations, further research into an appropriate scale would minimise conceptual confusion, increase clinicians’ understanding and control of CINVR, decrease patient distress and could have equal utility in both a clinical and a research setting.     

Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting

Goals of work  Ginger has been used to treat numerous types of nausea and vomiting. Ginger has also been studied for its efficacy for acute chemotherapy-induced nausea and vomiting (CINV). However, its efficacy for delayed CINV in a diverse oncology population is unknown. Materials and methods  We performed a randomized, double-blind, placebo-controlled trial in 162 patients with cancer who were receiving chemotherapy and had experienced CINV during at least one previous round of chemotherapy. All participants were receiving a 5-HT₃ receptor antagonists and/or aprepitant. Participants were randomized to receive either 1.0 g ginger, 2.0 g ginger daily, or matching placebo for 3 days. The primary outcome was change in the prevalence of delayed CINV. Secondary outcomes included acute prevalence of CINV, acute and delayed severity of CINV, and assessment of blinding. Main results  There were no differences between groups in the prevalence of delayed nausea or vomiting, prevalence of acute CINV, or severity of delayed vomiting or acute nausea and vomiting. Participants who took both ginger and aprepitant had more severe acute nausea than participants who took only aprepitant. Participants were able to accurately guess which treatment they had received. Ginger appeared well tolerated, with no difference in all adverse events (AEs) and significantly less fatigue and miscellaneous AEs in the ginger group. Conclusions  Ginger provides no additional benefit for reduction of the prevalence or severity of acute or delayed CINV when given with 5-HT₃ receptor antagonists and/or aprepitant. This trial is registered in ClinicalTrials.gov ID: NCT00065221.     

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.     

Acupuncture and acupressure for the prevention of chemotherapy-induced nausea—a randomised cross-over pilot study

Objective To investigate whether a combination of acupuncture and acupressure is effective for reducing chemotherapy-induced nausea and vomiting.Patients and methods In a randomised cross-over trial, 28 patients receiving moderately or highly emetogenic chemotherapy and conventional standard antiemesis were treated for one chemotherapy cycle with a combination of acupuncture and acupressure at point P6 and for one cycle at a close sham point. The main outcome measure was a nausea score derived from daily intensity rating.Results There was no difference between combined acupuncture and acupressure treatment at P6 and at the sham point for the nausea score, but the level of nausea was very low in both phases. The mean nausea score was 6.2 (standard deviation 9.0) for treatment at P6 and 6.3 (9.1) for treatment at the sham point (mean difference −0.1, 95% confidence interval −3.9 to 3.7; p=0.96). Seventeen of 21 participants completing the study would desire acupuncture and acupressure for future chemotherapy cycles, but there was no clear preference for either point.Conclusion In this small pilot study a significant difference between treatment at P6 and a close sham point could not be detected. However, it cannot be ruled out that an existing difference was missed due to the small sample size.     

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.     

Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy

 Lower hemibody radiotherapy is an effective palliative treatment for patients with widespread bone metastases, but is frequently associated with the unpleasant side effects of nausea and vomiting. Patients often require admission to hospital for at least an overnight stay, with its inevitable costs. This study has investigated the clinical efficacy and safety profile of ondansetron, a 5HT₃ receptor antagonist, and compared it to a standard antiemetic combination, chlorpromazine and dexamethasone. Sixty-six patients were randomised to receive antiemetic prophylaxis with either oral ondansetron or a combination of chlorpromazine and dexamethasone (33 patients in each arm): 60 were treated with lower abdominal radiotherapy (8 Gy mid-plane dose) and 6 with radiotherapy to the upper lumbar spine (12.5 Gy incident dose). Patients were assessed for severity of nausea and vomiting and for whether they would use the same antiemetic again. Quality of life was assessed using the Functional Living Index Cancer (FLIC) and Functional Living Index Emesis (FLIE) quality-of-life questionnaires. A detailed cost–benefit analysis was also performed. Ondansetron scored highly as an antiemetic, being significantly better at controlling emesis on all four study days (P<0.001) and significantly better at controlling nausea on day 1 (P<0.001) than the standard combination of chlorpromazine and dexamethasone. Quality of life was better in the ondansetron-treated group, and ondansetron was found to be safe with no significant adverse effects. As a result, 98% of patients and investigators would use ondansetron again. Cost–benefit analysis revealed that, when complete control of emesis is the aim, ondansetron is not unduly expensive compared to the standard antiemetic regimen. As ondansetron was clearly effective in patients receiving hemibody irradiation it seems it would be prudent to adopt it for use in such patients routinely. The use of ondansetron would allow them to be treated as outpatients, with the attendant financial and psychosocial benefits of such an approach.     

Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting — the Nordic experience

An open,noncomparative, Nordic multicenter study was carried out during 1991–1992 to evaluate the 5-HT₃ receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1–19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%–73% (days 2–6) in the complete series. Treatment efficacy remained stable (60%–79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P<0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course,but not later on. There were no differences in delayed nausea and vomiting. Sex and age were significant prognostic factors with regard to antiemetic response. Adverse events were recorded in 19%–37% of the cases during long-term follow-up. Headache (18%) and constipation (8%) were most frequent. The side effects were mild, however, and tropisetron (Navoban) was a safe drug and was well tolerated by the patients.