Emetic potential of daily oral etoposide

Background Chemotherapeutic agents are classified by their degree of emetogenicity. Highly and moderately emetogenic agents require antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. Intravenous etoposide is listed as having low emetic potential. However, oral etoposide is categorized as having moderate emetogenicity. Daily oral etoposide is used in refractory germ cell cancer patients. We prospectively evaluated the emetic potential of oral etoposide in this patient population.Materials and methods Between August 2003 and February 2006, 16 patients with refractory germ cell cancer received single-agent, daily oral etoposide 50 mg/M² for 21 consecutive days every 4 weeks. All patients had progressed after cisplatin combination chemotherapy and had received high-dose chemotherapy with carboplatin plus etoposide (intravenously) with peripheral blood stem cell transplant. No patient received prophylactic antiemetics. Patients completed a six-question Multinational Association of Supportive Care in Cancer (MASCC) antiemetic tool during each day of etoposide during the first 21-day course. Nausea intensity and duration were recorded. Number of emetic episodes and any antiemetic medications were recorded.Results All 16 patients completed the six-question MASCC form. Eleven of 16 had no nausea or vomiting and two other patients had only minimal nausea, despite absence of any prophylactic antiemetics. Only two patients required antiemetic support. Two patients experienced emesis for a single episode. One patient had nausea on days 9–20 with a MASCC rating of 3–6, and one patient had continued mild nausea (MASCC rating 1–3) for all 21 days.Conclusions Daily oral etoposide has a low probability of producing chemotherapy-induced nausea and/or vomiting and, in our opinion, does not require prophylactic antiemetics.     

Antiemetic therapy for multiple-day chemotherapy and high-dose chemotherapy with stem cell transplant: review and consensus statement

The objective of this paper is to evaluate the efficacy of modern antiemetic therapy for chemotherapy-induced nausea and vomiting for patients receiving multiple-day or high-dose chemotherapy. Published phase II and phase III studies as well as their personal experiences were evaluated by the authors to develop this consensus statement. The largest published experience with multiple-day chemotherapy is with 5-day cisplatin combination chemotherapy. The introduction of 5-HT3 antagonists greatly improved emetic control. However, day 4–5 nausea as well as delayed nausea and vomiting remains a clinical problem despite the inclusion of dexamethasone. A 5-HT3 antagonist plus dexamethasone is the preferred current option for patients receiving high-dose chemotherapy with stem cell transplant. However, the results do not appear as successful as for highly emetic standard-dose chemotherapy.     

Using aprepitant as secondary antiemetic prophylaxis for cancer patients with cisplatin-induced emesis

Purpose

Chemotherapy-induced emesis remains a problem despite prophylaxis with 5-hydroxytryptamine (5-HT3) antagonists and dexamethasone. The purpose of the current study was to evaluate the efficacy of adding aprepitant, a neurokinin-1(NK-1) receptor antagonist, as a secondary antiemetic prophylaxis in cases failing to achieve full protection against emesis during the first cycle of a cisplatin-based regimen.

Methods

Patients receiving chemotherapy with a dose of at least 50?mg/m² of cisplatin-based regimens were eligible. If patients failed to achieve complete protection against vomiting when antiemetics (5-HT3 antagonists and dexamethasone) were given in cycle 1, aprepitant was added in subsequent cycles. The primary endpoint was complete response (no emetic episodes and no rescue antiemetics) during days 1–6.

Results

We analyzed 257 patients consecutively. Forty-nine patients (19%) had acute and/or delayed emesis during the first cycle of chemotherapy. Forty of 49 patients received aprepitant for secondary prophylaxis of emesis in the second cycle. Complete protection from vomiting and nausea was achieved in 63% and 55% of patients, respectively. Thirty-five patients received aprepitant for the third cycle. Complete protection from vomiting and nausea was achieved in 77% and 71% of patients, respectively.

Conclusions

Primary antiemetic prophylaxis with 5-HT3 antagonists plus dexamethasone provided more than 80% complete protection against cisplatin-induced emesis. Addition of aprepitant as secondary antiemetic prophylaxis in subsequent cycles provided adequate emesis protection in patients who failed primary prophylaxis. Using aprepitant as secondary antiemetic prophylaxis for cancer patients with cisplatin-induced emesis is feasible and cost-effective.     

Oral ondansetron is highly active as rescue antiemetic treatment for moderately emetogenic chemotherapy: results of a randomized phase II study

Aims  In the present phase II randomized study, two different schedules of ondansetron were investigated as rescue antiemetic treatment for delayed emesis related to moderately emetogenic chemotherapy (MEC). Materials and methods  Patients scheduled to receive a first course of MEC were randomized to ondansetron 8 mg intramuscularly (arm A) or ondansetron 16 mg orally (arm B) as rescue antiemetic treatment for delayed emesis. Efficacy and safety evaluation was performed from days 2 to 6 through the administration of a diary plus a questionnaire in which the emetic episodes and the use of the assigned rescue treatment were recorded. All patients received standard prophylaxis for delayed emesis with oral dexamethasone 8 mg daily for 4 days starting on day 2. Results  Eighty-nine patients were enrolled into the study, of whom 44 were randomized to arm A and 45 to arm B. Twenty-two patients in each arm developed grade 1–2 delayed nausea/vomiting, all of which recurred to the rescue study treatment. Oral ondansetron resulted superior to intramuscular ondansetron in terms of complete response for nausea (77.3% vs 40.9%, respectively, p = 0.01) and vomiting (81.8% vs 31.8%, respectively, p = 0.001). Both schedules resulted to be very well tolerated, and no differences in toxicity were observed between the two arms of treatment. Furthermore, personal satisfaction about the use of the assigned rescue study medication was significantly higher in arm B. Conclusions  Due to its high efficacy and excellent tolerability, oral ondansetron is an important option in the management of MEC-related delayed emesis refractory to standard antiemetic prophylaxis.     

Patient-controlled antiemesis for cancer chemotherapy-induced nausea and vomiting

Nausea and emesis during cancer chemotherapy are very common, but can often be controlled with repetitive boli of antiemetic drugs. However, some patients, especially those with anticipatory symptoms, experience nausea and emesis despite antiemetic prophylaxis. An increased participation of these patients in the prophylaxis and treatment of these highly subjective symptoms may lead to better palliation. A patient controlled infusion pump was assessed in nine patients receiving cisplatin, in whom high-dose metoclopramide (5 mg/kg) had failed (>3 emetic episodes) during previous treatment cycles. Improved palliation was achieved in every case with on-demand boli in combination with a continuous infusion of metoclopramide or droperidol. Eight of the nine patients preferred the patient-controlled system to the conventional fixed-dose bolus regimens. The infusion pump functioned safely and reliably. Antiemetic treatment with the patient-controlled device was superior to previous conventional methods in this group of diffcult-to-treat patients.     

Antiemetic efficacy of combination therapy with granisetron plus prednisolone plus the dopamine D2 antagonist metopimazine during multiple cycles of moderately emetogenic chemotherapy in patients refractory to previous antiemetic therapy

 Effective antiemetic treatment of patients who have previously experienced chemotherapy-induced nausea and vomiting is difficult. The aim of this study was to evaluate the antiemetic efficacy of a single intravenous dose of granisetron plus a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day in patients refractory to previous antiemetic treatment with granisetron or with prednisolone plus metopimazine. The study population was made up of 25 consecutive women with stage I or II breast cancer, who were treated with multiple cycles of adjuvant cyclophosphamide, fluorouracil plus methotrexate or cyclophosphamide, epirubicin plus fluorouracil given i.v. every 3 weeks. Patients received the three-drug combination of antiemetics during a total of 113 cycles of chemotherapy. No emetic episodes were reported in 88.9% cycles on day 1, in 94.7% cycles on days 2 through 5 and in 85.8% cycles on days 1 through 5 after chemotherapy. No nausea was reported in 43.4% cycles on day 1, in 49.6% cycles on days 2 through 5 and in 34.5% cycles on days 1 through 5. Nineteen patients (76.0%) completed the scheduled nine cycles of chemotherapy, 1 being withdrawn because of ≥5 emetic episodes and 5, because they were not satisfied with the antiemetic treatment. The treatment was well tolerated. In conclusion, granisetron plus prednisolone plus metopimazine is a highly effective antiemetic treatment in patients receiving moderately emetogenic chemotherapy refractory to antiemetic therapy with granisetron or prednisolone plus metopimazine. Published online: 25 February 2000     

国产盐酸帕洛诺司琼注射液预防化疗所致恶心呕吐的随机对照研究

目的评价盐酸帕洛诺司琼预防高度催吐危险的化疗方案所致恶心、呕吐的疗效和安全性。方法将符合纳入标准的恶性肿瘤患者随机分入AB组和BA组,于化疗前30min缓慢静推盐酸帕洛诺司琼或盐酸托烷司琼。观察化疗后5d内恶心、呕吐情况,以及不良反应。结果共纳入24例患者,可评价18例。2种药物对恶心、急性呕吐的完全控制率及有效控制率,以及对迟发性呕吐的完全控制率比较,无显著差异,而盐酸帕洛诺司琼对迟发性呕吐的有效控制率显著高于盐酸托烷司琼。2种药物不良反应较少且程度较轻。结论盐酸帕洛诺司琼预防高度催吐危险的化疗方案所致恶心和急性呕吐的疗效与盐酸托烷司琼相当,但预防迟发性呕吐的疗效优于盐酸托烷司琼,且不良反应发生率低、程度轻。     

Medroxyprogesterone acetate for refractory emesis in Cisplatin-treated patients

Abstract Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing side effects in systemic chemotherapies. Recently, several effective agents have been developed to prevent CINV, and CINV can be prevented in 70%-80% of patients receiving chemotherapies. Conversely, 20%-30% of patients still suffer from CINV despite recommended optimal antiemetic preventions. Refractory emesis is defined as emesis occuring despite the use of antiemetic prophylaxis during the previous cycle of chemotherapy. Salvage treatments for refractory emesis are necessary, but there are few effective treatments at present. We consider medroxyprogesterone acetate to be a potentially promising agent for refractory emesis. We encountered three cases in which medroxyprogesterone acetate was extremely effective for refractory emesis induced by cisplatin-containing chemotherapy.     

Delayed emesis: incidence, pattern, prognostic factors and optimal treatment

Delayed emesis has been arbitrarily defined as vomiting and/or nausea beginning, or persisting for, more than 24 h after chemotherapy administration. Acute emesis is the most important prognostic factor for delayed emesis. Owing to the relatively high incidence and severity all patients treated with cisplatin > or = 50 mg/m(2) should receive antiemetic prophylaxis. In these patients a combination of dexamethasone plus metoclopramide or a 5-HT3 antagonist is the most efficacious regimen. All patients submitted to moderately emetogenic chemotherapy, such as cyclophosphamide, carboplatin, doxorubicin and epirubicin, should also receive antiemetic prophylaxis with oral dexamethasone to prevent delayed emesis.     

Control of emsis by intravenous granisetron in breast cancer patients treated with 5-FU,epirubicin and cyclophosphamide

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT₃) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0–2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%–98% and 77%–93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect folloed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.     

肿瘤化疗所致恶心呕吐现状调查

目的调查化疗所致恶心呕吐（chemotherapy—inducednauseaandvomiting,CINV）的患者心理预期和发生情况,并评估CINV对患者生活质量的影响,为提高临床医生对CINV的认识和重视提供依据。方法采用问卷调查的方式,调查华中科技大学同济医学院附属同济医院使用中度致吐风险化疗（MEC）或高度致吐风险化疗（HEC）的患者,并对其进行连续两周期相同化疗方案的随访。患者分别于化疗开始前、化疗第2天和化疗第6天,记录化疗期间急性、延迟性恶心呕吐发生情况、自主止吐用药和CINV对生活功能的影响,调查结果采用描述性分析和多元线性回归分析。结果本研究共调查344例患者,最终303例患者完成问卷调查。结果显示：单日化疗MEC组急性、延迟性和总的完全缓解率分别为86．1％、76．6％和71．5％,HEC组为84．1％、71．0％和66．7％。多日化疗患者分别为93．8％、64．9％和64．9％;第2周期化疗前患者关于恶心呕吐预期值和焦虑值与患者前一周期化疗延迟性恶心发生的严重程度密切相关;约30％的患者因CINV对生活功能造成负面影响。结论在行中度和高度致吐风险化疗的患者中,CINV治疗现状仍存在较大问题,尤其是在延迟期反应和恶心症状的控制方面。在临床实践中需进一步加强对CINV的关注,并提供更加有效的治疗措施。     

Superiority of methylprednisolone sodium succinate over low dose metoclopramide hydrochloride in the prevention of nausea and vomiting produced by cancer chemotherapy

Methylprednisolone sodium succinate and metoclopramide were compared for their efficacy, tolerance, and safety in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy in patients with cancer. Previously untreated patients about to receive at least 2 cycles of identical chemotherapy were entered into a study using a randomized, double-blind, crossover design. Patients were given either 250 mg of methylprednisolone or 10 mg of metoclopramide intravenously before the first cycle of chemotherapy and were then crossed over to receive the alternate medication before the second cycle of chemotherapy. Prochlorperazine was prescribed in both cycles for postchemotherapy nausea and vomiting. After each treatment cycle patients recorded the degree of nausea, drowsiness and anxiety, the number of episodes of vomiting experienced, and the amount of prochlorperazine taken. After the second treatment cycle patients recorded their preference for either the first or the second antiemetic medication with respect to nausea, vomiting, and overall effectiveness. Of 157 patients entered into the study, 115 were fully appraisable. Methylprednisolone was superior to metoclopramide in preventing nausea and vomiting and in decreasing anxiety and the amount of prochlorperazine used. A majority of the patients expressing a preference preferred methylprednisolone to metoclopramide for control of nausea (p = 0.003), control of vomiting (p = 0.0006), and overall effectiveness (p = 0.00004). There were few side-effects. We conclude that methylprednisolone may have some utility as an antiemetic in patients receiving moderately emetogenic chemotherapy, and who are treated as outpatients.     

Optimal selection of antiemetics in children receiving cancer chemotherapy

 Only a few studies have been carried out specifically on the prevention of nausea and vomiting in children receiving chemotherapy. In these patients older antiemetic drugs such as metoclopramide and phenothiazines had moderate efficacy and induced significant side effects, especially marked sedation and extrapyramidal reactions. In comparative trials the 5-HT₃ receptor antagonists have shown better efficacy and tolerability than chlorpromazine or metoclopramide combined with dexamethasone. The combination of a 5-HT₃ receptor antagonist plus dexamethasone is superior to a 5-HT₃ receptor antagonist alone and should be the standard antiemetic prophylaxis in all paediatric patients receiving highly or moderately emetogenic chemotherapy. The optimal dose and scheduling of these antiemetic drugs need to be studied, as well as the antiemetic efficacy, in the prevention of chemotherapy-induced delayed and anticipatory emesis in children.     

Antiemetic activity of megestrol acetate in patients receiving chemotherapy

Purpose

Several trials had independently noted that patients receiving megestrol acetate had less nausea and vomiting, but this antiemetic activity of megestrol acetate has not been reported separately in the literature. Our objective was to evaluate the antiemetic ability of megestrol acetate in patients receiving chemotherapy.

Patients and Methods

Patients receiving chemotherapy were randomly assigned to receive either megestrol acetate 320?mg PO or placebo before the first day of chemotherapy, followed on days 1?C4 by megestrol acetate 320?mg PO combined with granisetron 3?mg IV and metoclopramide 20?mg IM or only granisetron 3?mg IV combined with metoclopramide 20?mg IM in a crossover manner during two consecutive cycles. Rates of complete protection against both vomiting and moderate-to-severe nausea was the primary end point.

Results

One hundred patients were enrolled in the study. The antiemetic regimen containing megestrol acetate was superior in providing complete protection from nausea and vomiting (45% megestrol acetate regimen vs.17% no megestrol acetate regimen). Complete response of acute phase in both antiemetic regimens was different (85% megestrol acetate regimen vs. 72% no megestrol acetate regimen). Complete response of delayed emesis was also different (49% megestrol acetate regimen vs. 18% no megestrol acetate regimen). Adverse events were mostly mild to moderate. There were no serious drug-related adverse events between the two antiemetic regimens.

Conclusion

Megestrol acetate was shown to be an effective antiemetic agent. Megestrol acetate might be a new antiemetic option for chemotherapy.     

Single high-dose dexamethasone improves the effect of ondansetron on acute chemotherapy-induced nausea and vomiting but impairs the control of delayed symptoms

The introduction of serotonin receptor (5-HT₃) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m₂), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.     

Assessment of the emetogenic potential of intrathecal chemotherapy and response to prophylactic treatment with ondansetron

 The purpose of this study was to document the emetogenic potential of intrathecal chemotherapy (IC) in children and to evaluate the efficacy of ondansetron in reducing nausea and vomiting with this chemotherapy treatment. Patients less than 18 years of age with acute lymphoblastic leukemia were eligible to participate in a survey project measuring the emetogenic potential of various chemotherapy treatments. Patients surveyed for 1 or more IC treatments were included in this report. The IC consisted of methotrexate, hydrocortisone and cytarabine, dosed according to patient age. A nausea/vomiting survey instrument was completed by each patient and/or parent following IC treatment. The instrument rated nausea, vomiting and daily activity interference (DAI) on a 4-point scale of 0=none, 1=mild, 2=moderate and 3=severe, and collected data on the number of vomiting and/or retching episodes in addition to the child's appetite following the chemotherapy treatment. When ondansetron was employed, it was administered in an i.v. infusion at a dose of 0.15 mg/kg before and after chemotherapy or as an oral dose of 4 mg or 8 mg before chemotherapy. Courses of IC without antiemetics were analyzed to determine the emetogenic potential of IC. For patients receiving IC both with and without ondansetron, courses were compared with each patient used as their own control to determine the influence of ondansetron upon survey responses. Statistical analysis consisted of nonparametric Friedman 2-way ANOVA for ordinal variables and a paired t-test for continuous variables. The binomial test was employed to analyze for differences between ondansetron and no antiemetic in the number of patients with complete control of both nausea and vomiting or vomiting alone. A total of 63 children with a mean age of 7.6±4.2 years were each studied on one or more occasions. Thirty-seven children were surveyed for 87 IC treatments without antiemetics (group I), and 17 children from this group were surveyed for 48 IC courses with i.v. ondansetron (group IA). An additional 18 children were subsequently surveyed for 39 IC courses with i.v. ondansetron (group II). Fifteen patients (7 of whom were members of group I) were surveyed following 33 IC courses with oral ondansetron (group III). The survey scores for group I patients were: nausea severity 1.3±1.1, vomiting severity 1.2±1.1, DAI 1.2±1.0 and mean number of emetic episodes 4.7±8.4. The mean appetite score was 1.5±1.1. For patients in group IA, nausea severity (0.8±0.9), vomiting severity (0.5±0.8), DAI (0.7±0.8), and the number of emetic episodes (1.4±2.8) were all significantly lower than with prior IC treatments without ondansetron. For complete protection, children receiving i.v. ondansetron had greater complete protection rates from both nausea and vomiting or vomiting alone than did patients receiving no antiemetic. Survey responses were also lower for patients receiving oral ondansetron, but insufficient control data did not allow for statistical analysis. IC results in mild to moderate nausea and vomiting in children. The emetogenic potential of IC is significantly reduced by i.v. ondansetron.     

The impact of chemotherapy-induced nausea and vomiting on health-related quality of life

Goal of work The objectives of this prospective observational study were to estimate the frequency of patients who reported an impact of chemotherapy-induced nausea and vomiting (CINV) on their daily life and to evaluate the determinants of such an impact. Materials and methods Adult cancer patients at seven Italian oncology centers who were receiving cisplatin-containing regimens reported incidence and intensity of CINV for eight consecutive days in a diary and completed a Functional Living Index for Emesis (FLIE) questionnaire. Main results Overall, 34% of patients reported vomiting and 62% reported nausea after chemotherapy. On days 1 to 5 after receiving chemotherapy, 67% of patients who had at least one emetic episode and 77% of those who suffered from at least mild nausea experienced an impact on their daily activities as measured on the FLIE questionnaire. More than 90% of all patients with both acute and delayed nausea or vomiting reported an impact on their daily life. Both acute and delayed vomiting contributed in similar measure to impact daily life; however, the importance of delayed nausea was greater than that of acute nausea. Conclusions Despite antiemetic prophylaxis, CINV is still prevalent and often impacts the daily life of patients in Italy, especially in the delayed phase. The duration more than the severity seems to be responsible for the impact of CINV on the patients’ daily lives.     

Methodology of antiemetic trials: response assessment, evaluation of new agents and definition of chemotherapy emetogenicity

 Establishing appropriate and practical methodology is a key to progress in the investigation of chemotherapy-induced nausea and vomiting. Critical issues include patient response assessment, proper trial design for evaluating new agents, and the definition of chemotherapy emetogenicity. In assessing antiemetic response, the primary end-point should be complete control of emesis and nausea. Emesis and nausea should be independently assessed with the period of observation defined (acute, delayed, anticipatory). Emesis can be evaluated by measuring the number of emetic episodes either by direct observation or by patient self-report using patient-completed diaries. Nausea should be measured by patient self-report with the standard parameters, including frequency and intensity. New antiemetic drug development should proceed in an orderly progression from open-label phase I–II trials defining tolerance and minimally fully effective dose to phase III comparative trials. A randomized, parallel, double-blind study is the preferred design for the latter, and the comparator arm should always include the current best available treatment. Antiemetic placebos are no longer acceptable with chemotherapy regimens known to produce emesis in a majority of patients. None of the emetogenic classifications proposed to date adequately accounts for all known important patient- and treatment-related prognostic variables. A modification of a recently reported schema is proposed for use in making antiemetic treatment recommendations and defining the emetogenic challenge in clinical trials.     

Granisetron plus dexamethasone in moderately emetogenic chemotherapy: evaluation of activity during three consecutive courses of chemotherapy

In this study we evaluated the antiemetic activity of a combination of 3 mg granisetron in a short i.v. infusion followed by 12 mg dexamethasone i.v. in 64 patients with cancer receiving moderately emetogenic chemotherapy scheduled in a single day. No patient had previously undergone chemotherapy and three consecutive cycles were evaluated. Response to antiemetic treatment was graded as follows: complete response, no episodes of vomiting; major response, only one episode; minor response, two to four episodes; failure, more than four episodes. Nausea was graded as absent, mild, moderate or severe (patients bedridden). At the first cycle a complete protection from acute vomiting and nausea was achieved in 95% and 73% of patients respectively; the rate of complete response for delayed vomiting was 90%, while 45% of patients complained of delayed nausea. The antiemetic and antinausea efficacy remained substantially unchanged during the second and third cycles of chemotherapy. Constipation and headache were the most frequent adverse events. In conclusion this antiemetic regimen appears very effective in preventing nausea and vomiting in moderately emetogenic chemotherapy.     

Palonosetron and prednisolone for the prevention of nausea and emesis during fractionated radiotherapy and 5 cycles of concomitant weekly cisplatin—a phase II study

Purpose

Recommendations for antiemetic prophylaxis supportive to radiotherapy and concomitant chemotherapy are not evidence-based. The purpose of this study was to evaluate the efficacy of the antiemetic regimen concurrent to fractionated radiotherapy and concomitant weekly cisplatin in two Danish departments of oncology.

Methods

Patients with gynecological cancer scheduled to receive fractionated radiotherapy and concomitant weekly cisplatin (40 mg/m²) were asked to complete a study diary in order to assess episodes of emesis, grade of nausea, and use of rescue antiemetic treatment daily during 5 weeks of treatment. Antiemetic treatment consisted of palonosetron and prednisolone. A patient had completed the study if emesis occurred or if 5 weeks of treatment were accomplished without emesis. The primary endpoint was sustained no emesis during 5 weeks of treatment.

Results

A total of 48 patients completed 155 weekly cycles of radiotherapy, concomitant weekly cisplatin, and antiemetic prophylaxis. The probability of completing 5 cycles without emesis (sustained no emesis) was 57 %. During cycle 1, 42 % of the patients were free from nausea. After 5 cycles, only 23 % of patients were continuously free from nausea. One half of the patients used rescue antiemetic treatment at least once during the 5 cycles.

Conclusion

The present study demonstrates that an antiemetic prophylaxis consisting of palonosetron and prednisolone is insufficient for the prevention of nausea and vomiting induced by radiotherapy and weekly cisplatin in patients treated for gynecological cancer. The addition of a neurokinin-1 receptor antagonist should be investigated in a randomized, double-blind study in this setting.