Measuring psychological and physical distress in cancer patients: structure and application of the Rotterdam Symptom Checklist

Use of the Rotterdam Symptom Checklist (RSCL) to measure psychological and physical distress as experienced by cancer patients, is discussed in this paper. The stability of the structure of the RSCL was assessed in principal component analyses in three studies: one concerning cancer patients during either chemotherapy or follow-up (n = 86), one done in patients undergoing chemotherapy for advanced ovarian cancer (n = 56), and the third dealing with cancer patients under treatment, disease-free 'patients', and 'normal' controls (n = 611). The psychological dimension proved to be stable across populations. A scale based on this factor was highly reliable (Cronbach's alpha 0.88-0.94). The physical distress is reflected by several dimensions in a homogeneous population (pain, fatigue, gastrointestinal complaints) and undimensionally in a heterogeneous population. Reliability of the physical distress scales is good (0.71-0.88). The current components of the RSCL and the use of individual and disease specific symptoms are discussed.     

Improvement in the control of chemotherapy induced emesis with ondansetron, methylprednisolone and lorazepam combination in patients treated by a moderate emetic treatment and uncontrolled by a previous antiemetic combination

The objective of this double blind parallel-group multicentre study was to compare the efficacy and safety of the combination ondansetron + methylprednisolone + lorazepam (O + M + L) in the prevention of emesis induced by chemotherapy with cyclophosphamide or adriamycin . This tritherapy was compared to a bitherapy O + M. Patients included were suffering from severe haemopathy or breast cancer. They had to have an incomplete response to a previous antiemetic association of 5HT3 serotoninergic receptor antagonist and corticoid. One hundred and thirty-five adult patients were included and were randomised to receive : O + M + L or O + M for 3 days. The emesis control during the 3 days of treatment (no emetic episode during the complete course) was significantly superior in the group O + M + L than in the group O + M (69% versus 46%, p = 0. 042); nausea control on the worst day of the cure was significantly superior in the group O + M + L than in the group O + M (p = 0.04) with 76% of patients in the group O + M + L having complete or major nausea control compared to 51% in the group O + M. The stability of quality of life during the days following chemotherapy measured by one questionnaire, including two scales, one cancer specific (FLIC) and one emesis specific (FLIE), appeared significantly better in group O + M + L (p = 0.04 and p = 0.019). Safety of both antiemetic regimens was good and similar between the two treatment groups. This trial shows that the adjunction of lorazepam to ondansetron and corticoid in combination increases the antiemetic control for patients with an incomplete response to a previous regimen containing a 5HT3 serotoninergic receptor antagonist and a corticosteroid in the prevention of chemotherapy-induced emesis.     

A randomized, double-blinded study comparing six doses of batanopride (BMY-25801) with methylprednisolone in patients receiving moderately emetogenic chemotherapy.

Several agents in a new class of antiemetic compounds, 5-hydroxytryptamine (5-HT3) antagonists, have shown promise as effective antiemetics with fewer side effects than metoclopramide. One of these agents, batanopride, produced no severe toxicity at doses that prevented emesis due to chemotherapy in early Phase I trials. We conducted a randomized, double-blinded, 7 arm clinical trial to: (1) identify the presence of a dose-response for complete protection from emesis, and (2) compare batanopride with a standard antiemetic, methylprednisolone if a dose-response was found not to exist. Prior to chemotherapy, six patient groups each received a single intravenous dose of batanopride ranging from 0.2 to 6.0 mg/kg whereas a seventh group received methylprednisolone 250 mg intravenously. Chemotherapy-na?ve cancer patients scheduled to receive moderately emetogenic chemotherapy were eligible. Primary treatment outcomes that were recorded and analyzed included the number of episodes of emesis, the time to the first episode of emesis as well as the frequency and severity of nausea. Two hundred and eight patients accrued between April 1989 and February 1990 were evaluable for response. A significant dose-response effect for complete protection from emesis was not seen over the first 24 hours after chemotherapy (p = 0.102). However, a linear dose-response effect for time to first emesis was evident in a multivariate analysis (p = 0.029). While the highest batanopride dose group was associated with a higher complete protection rate (CPR) than the control group, this group also exhibited a higher incidence of diarrhea (p = 0.013), hypotension, and electrocardiographic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aprepitant as salvage therapy in patients with chemotherapy-induced nausea and emesis refractory to prophylaxis with 5-HT(3) antagonists and dexamethasone

BACKGROUND: Despite prophylaxis with 5-HT(3) antagonists and dexamethasone, nausea/emesis are common chemotherapy- induced toxicities. The aim of this trial was to evaluate the efficacy of adding the NK1 antagonist aprepitant in patients refractory to standard prophylaxis. PATIENTS AND METHODS: Patients with significant nausea/vomiting despite prophylaxis with 5-HT(3) antagonists and dexamethasone were eligible. Aprepitant was added to the same antiemetic regimen used during previous cycles. RESULTS: 34 patients received 92 cycles of chemotherapy with aprepitant which was applied orally at 125 mg on day 1 and 80 mg on days 2 and 3. All patients were refractory to standard antiemetic prophylaxis during cisplatin-based (n = 12) or other chemotherapy (n = 22). With the addition of aprepitant, all patients reported subjective improvement. The number of patients with nausea for >4 days decreased from 24 (71%) to 4 (12%) (p < 0.001), and the number of those with emesis for >2 days decreased from 26 (77%) to 0 (0%) (p < 0.001). In 12 patients receiving aprepitant for >2 cycles (3-8) the efficacy was maintained. No toxicity possibly related to aprepitant was observed. CONCLUSION: Aprepitant demonstrated significant activity in patients with nausea/vomiting refractory to prophylaxis with 5-HT(3) antagonists and dexamethasone.     

Control of refractory, chemotherapy-induced emesis with the serotonin antagonist ondansetron (GR38032F).

Twenty-four patients with severe post-chemotherapy emesis (greater than 15 emetic episodes) refractory to prior combination antiemetic therapy were treated with a selective 5-HT3 receptor antagonist ondansetron (GR38032F). Ondansetron was given as 8 mg three times daily orally for 5 days with the first dose given 1 h prior to chemotherapy. Control of emesis was evaluated over the 5-day period. All chemotherapy was administered on an outpatient basis. Worst day analysis of antiemetic response was 87.5%: complete protection in 9/24 patients (37.5%) and major protection (1-2 emetic episodes) in 12/24 patients (50%). No protection from emesis was observed in 3 patients (12.5%). No side effects and no alterations in liver function tests were observed. Ondansetron is a safe and highly effective antiemetic agent.     

Comparison of the Emetogenic Potential Between Cisplatin and Carboplatin in Combination with Alkylating Agents

Platinum-based poh chemotherapy is widely used in the treatment of gynecological cancer. Emesis is one of the most disturbing side-effects of platinum therapy. We performed a study to evaluate and compare the emetogenic potential and the different emesis pattern after cisplatin and carboplatin under antiemetic treatment with ondansetron. One hundred and twenty-two patients with either cisplatin-con-taining (n = 70) or carboplatin-containing (n = 52) first-line chemotherapy were included. Treatment with cisplatin led more frequently to emesis and patients suffered from more severe emesis than carboplatin treated patients. Delayed emesis was observed after both platinum analogues but occurred more frequently and lasted longer after cisplatin.     

Anti-emetic efficacy of oral granisetron in the total control of late-onset emesis induced by cyclophosphamide-containing chemotherapy

Introduction

Effectiveness of 5-HT₃ receptor antagonists in preventing cyclophosphamide-induced emesis suggests that it is mediated by serotonin release. Since urinary 5-hydroxyindoleacetic acid (5-HIAA) is not significantly increased, the mechanism of emesis induction remains poorly understood, and the usefulness of these drugs in late-onset emesis prevention remains controversial.

Material and methods

In this randomised, double-blind, and placebo-controlled trial, 139 chemotherapy-naïve breast cancer patients received intravenous chemotherapy combinations containing cyclophosphamide at doses ≥500 mg/m². Total antiemetic control was the primary efficacy parameter. On day 0 all patients received intravenous granisetron (3 mg) prior to chemotherapy. On day 1 patients were randomly assigned either to oral granisetron (1 mg bid) or to placebo, for a 2-day course. Patients remained hospitalised during the study period. Rescue therapy (up to 2 doses of i.v. granisetron 3 mg) was promptly administered should there be a second episode of vomiting. Twenty-four hour urine samples were collected on days ?1 to +2, for analysis of 5-HIAA excretion.

Results

Relative to the control group, significantly more patients in the oral granisetron group experienced total control of emesis on day 1 (67% versus 49%; p=0.04), on day 2 (76% versus 52%; p<0.01), and on days 1–2 (60% versus 42%; p=0.04). Excretion of 5-HIAA was significantly increased on day 0, day 1 and day 2 compared to levels on day ?1 (p<0.01 for all paired comparisons). The type of chemotherapy administered and the patient's history of vomiting were the variables influencing the total control of emesis.

Conclusions

Oral granisetron provided high rates of effective and safe control of late-onset emesis induced by cyclophosphamide-based chemotherapy. Urinary excretion of 5-HIAA was significantly increased during the entire emesis period.     

Clinical evaluation of the simultaneous blockade of the dopamine D-2, Histamine H-1, and muscarinic cholinergic receptors in cancer chemotherapy-induced emesis: Results of a controlled trial

Summary Twenty-six patients being treated with 5-fluorouracil-adriamycin-cyclophosphamide (FAC), or vincristine-adriamycin-cyclophosphamide (VAC) chemotherapy completed a randomized, double-blind, cross-over study in which the antiemetic activity of thiethylperazine (6.5 mg p.o. every 8hx5 days) was compared with that of the combination of thiethylperazine (same dosage) plus amitriptyline (25 mg p.o. every 8hx5 days). This combination was designed to obtain a simultaneous blockade of the dopamine D-2, histamine H-1, and muscarinic cholinergic receptors of the central structures responsible for emesis (chemoreceptor trigger zone and vomiting center).The combination significantly decreased both the number of emetic episodes (P<0.05) and the duration of emesis (P<0.01) compared with thiethylperazine alone. The combination was also preferred by a significantly higher number of the patients (P<0.001) who were exposed to both the types of antiemetic treatment under trial.The combination of thiethylperazine plus amitriptyline was shown to have a satisfactory antiemetic activity against vomiting induced by VAC chemotherapy in males; it afforded major protection (two emetic episodes or fewer) in 83% of the cases. Nonetheless, it cannot be considered a satisfactory treatment for the control of vomiting induced by FAC chemotherapy in female patients, only 43% of whom achieved major antiemetic protection.     

枢复宁防止由非顺铂化疗所致呕吐的疗效观察

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

A phase II study of ondansetron as antiemetic prophylaxis in patients receiving carboplatin for advanced ovarian cancer. The North Thames Ovary Group.

Thirty four patients who were receiving carboplatin 400 mg/m2 for advanced epithelial ovarian cancer were treated with ondansetron antiemetic prophylaxis. Ondansetron was given as 4 mg oral +4 mg iv 30 minutes prior to carboplatin followed by 8 mg oral tds for 5 days. Of the evaluable patients complete or major control of emesis on day one was achieved in 94% of previously untreated patients and 81% of patients refractory to conventional antiemetic therapy. For the 5 day period as a whole 88% of untreated patients and 69% of those with refractory emesis reported complete or major control of nausea and vomiting. Fifteen patients noted no side effects with mild headache (30%) and constipation (21%) the most frequent problems in the remainder. Ondansetron is effective antiemetic prophylaxis for carboplatin chemotherapy and should allow the majority of these patients to be managed on an out-patient basis.     

Comparative trial of oral granisetron and intravenous ondansetron in patients receiving chemotherapy for breast cancer. Study Group of Granisetron

This multicentric randomized trial compared two strategies in the prevention of acute and delayed nausea and vomiting induced by moderately emetogenic chemotherapy in patients with breast cancer. The antiemetic efficacy and side effects of oral granisetron, followed by metoclopramide, were compared to those of intravenous (IV) ondansetron followed by oral ondansetron. 198 chemonaive patients with breast cancer, treated with a moderately emetogenic chemotherapy, were randomly assigned to receive either oral granisetron 1 mg twice a day on day 1, followed by metoclopramide, 60 mg on day 2 and 3, or ondansetron, 8 mg IV on day 1, followed by ondansetron 8 mg tablet twice a day on day 2 and 3. Both treatments have shown similar control of acute emesis: complete response was achieved in 71% of granisetron group and 66% of ondansetron, and total response in respectively 49% and 53%. However, granisetron plus metoclopramide showed a trend towards better efficacy than oral ondansetron in the prevention of delayed emesis. Furthermore, during the overall study period (day 1 to 5), the percentage of complete responses in the group receiving oral granisetron followed by oral metoclopramide was significantly higher than in the group receiving ondansetron (53% versus 37%; p = 0.022). In conclusion, oral granisetron has shown similar efficacy as IV ondansetron in the prevention of acute emesis induced by moderately emetogenic chemotherapy. Oral granisetron followed by metoclopramide seems more efficient than IV plus oral ondansetron in the prevention of delayed emesis.     

Prevention of delayed emesis induced by moderately emetogenic chemotherapy in patients with acute emesis

The rates of delayed nausea and vomiting by moderately emetogenic chemotherapy in patients with previous experience of acute emesis are usually quite high. This is a pilot study aiming to evaluate the safety of a new antiemetic schedule to prevent delayed emesis in this subset of patients. During 5 consecutive cycles of moderately emetogenic chemotherapy, we evaluated 50 patients (15 males) who experienced acute emesis in the first cycle of treatment. The regimen for prevention of delayed emesis consisted of daily tropisetron (5 mg orally from d 2 to d 6 of each chemotherapeutic cycle) associated to ACTH-Depot (1 mg intramuscularly 24 and 68 h after the initiation of chemotherapy). In 77% of chemotherapy cycles, there was a total elimination of nausea and vomiting, whereas in the remaining 23% of cycles, there was a major response defined as ≤ 2 vomiting episodes per cycle or nausea grade 1 according to the WHO. The efficacy of the antiemetic regimen persisted during the entire treatment program without the appearance of toxic effects. The proposed antiemetic regimen is highly active in preventing delayed nausea and vomiting episodes in patients receiving moderately emetogenic chemotherapy. Moreover, no toxic effects were observed. These promising results require confirmation by a randomized trial.     

Comparison of Ondansetron with Customary Treatment in the Prophylaxis of Nausea and Emesis Induced by Non-Cisplatin Containing Chemotherapy

One hundred cancer patients receiving non-cisplatin containing chemotherapy were entered in a prospective study in which the efficacy of ondansetron was compared with standard antiemetic treatments in the prophylaxis of nausea and emesis. During the first 24 h, 77% of patients on ondansetron reported complete control of emesis compared with 56% of those on customary treatments (p = 0.03). However, no statistically significant difference was observed between ondansetron and customary treatments in control of delayed emesis on days 2-5. Nor was any statistically significant difference seen between ondansetron and customary treatments in preventing acute or delayed nausea.     

Ondansetron versus Chlorpromazine for Preventing Emesis in Bone Marrow Transplant Recipients: a Double-Blind Randomized Study

Summary

Ondansetron, a selective 5-HT, antagonist, is known to be effective for preventing emesis induced by cisplatin and other antineoplastic agents. We undertook a randomized double-blind study in a series of bone marrow transplantation (BMT) recipients to assess the antiemetic efficacy and the safety of ondansetron in comparison with chlorpromazine, which was being used at our institution, as the standard antiemetic agent for the conditioning regimen. Forty patients submitted to BMT (21 autologous, 19 allogeneic) were included in the study. Patients were randomly assigned to receive ondansetron (as a loading dose of 8 mg iv one hour before the beginning of the conditioning regimen followed by a continuous infusion of 1 mg per hour for the whole treatment period) or chlorpromazine 60 mg/m²/day given by continuous infusion for the same period (maximum 8 days). Twenty patients were assigned to ondansetron, while 20 were assigned to chlorpromazine. The response rate in terms of antiemetic efficacy and in nausea control was similar between the two treatment groups. On the contrary the two groups differed significantly in regard to side-effects: patients receiving ondansetron experienced significantly less sedation (p = 0.002), the absence of extrapyramidal reactions (p < 0.001) and no need for dose reduction (p < 0.001) as compared with patients treated with chlorpromazine.     

Ondansetron (GR 38032F), a competitive 5-HT3 receptor antagonist as an antiemetic in cytostatic drug-induced nausea and vomiting. An open, substance-oriented phase II/III study

In an open, drug-oriented phase-II/III-study 24 patients were treated with the 5-HT3-antagonist Ondansetron as an antiemetic drug for chemotherapy-induced nausea and emesis. Patients with treatment regimen containing cisplatin were excluded. All patients had suffered from severe nausea and vomiting under conventional antiemetic drugs during a previous identical chemotherapy cycle and were treated with 8 mg Ondansetron t.d. on the day of the chemotherapy and on the four following days. The drug was given with 90 cytostatic cycles ranging from 1 to 14 cycles per patient. Only 2 patients (8%) did not experience an improvement of their symptoms in any of the treatment cycles as measured by a self-conducted grading of nausea and by the frequency of vomiting in comparison to a previous treatment cycle under conventional antiemetic therapy. Eleven out of 18 patients, who were treated with Ondansetron more than once (61%) noted a diminished frequency of vomiting in each treatment cycle with Ondansetron. Sixty of the 90 therapy cycles with Ondansetron resulted in complete (no vomiting) or major (one to two vomits within 24 h following chemotherapy) protection from emesis (37 and 29 per cent, respectively). The most frequent side effect noted was obstipation (7 patients), followed by slight diffuse abdominal pain (4 patients, probably also due to chemotherapy) and slight to severe headache (3 patients, 1 patient was therefore withdrawn from the study). No other side effects were seen. In conclusion, our study indicates that Ondansetron is an effective and safe drug for the treatment of cytostatic drug-induced nausea and vomiting.     

Neurokinin-1-receptor antagonists: a new approach in antiemetic therapy

Aprepitant (Emend), the first neurokinin-1-receptor antagonist (NK-1-RA), represents a new class of antiemetics. Aprepitant has been approved for the prevention and treatment of acute (0-24 h after chemotherapy) and delayed (1-5 days after chemotherapy) emesis resulting from cisplatin-based chemotherapy and moderately emetogenic chemotherapy. The addition of aprepitant to standard antiemetic therapy in cisplatin-based chemotherapy significantly improves emesis protection in general and, in particular, in the delayed phase by approximately 20%. Results from a recently published study in patients receiving moderately emetogenic chemotherapy suggest a benefit of aprepitant when combined with dexamethasone and a 5-HT(3) receptor antagonist for the prevention of acute emesis, followed by aprepitant as a single agent in the prevention of delayed emesis. Altogether, the addition of aprepitant to the standard antiemetic regimen (5-HT(3) receptor antagonist and dexamethasone) significantly improves the protection against vomiting in the acute as well as in the delayed phase in highly and moderately emetogenic chemotherapies. Therefore, the combination of a 5-HT(3) receptor antagonist, dexamethasone and aprepitant should be considered as a new standard antiemetic therapy.     

Aprepitant successful for controlling nausea and vomiting in a case having difficulty with control treatment in a standard antienemic therapy involving chemotherapy for gallbladder cancer postoperative recurrence

This case was a 62-year-old female. She underwent radical surgery for advanced gallbladder cancer 2 years ago after preoperative chemotherapy consisting of GEM/5-FU and CDDP (GFP). Two years after surgical treatment, multiple lung metastases and lymph node metastases appeared, and therefore, GFP chemotherapy was introduced. Rapid emesis occurred at two-cycle medication the first day, and was continued for several days. It was difficult to control the emesis by standard antienemic therapy. We therefore used aprepitant, a new medicine for antiemetic therapy. It had an excellent effect, and chemotherapy for this patient is still being continued.     

The antiemetic efficacy of methylprednisolone compared with metoclopramide in outpatients receiving adjuvant CMF chemotherapy for breast cancer: a randomized trial

A randomized trial was performed comparing the antiemetic efficacy of methylprednisolone (MPN) and metoclopramide (MCP) in 60 breast cancer patients eligible for outpatient adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-FU (CMF). At the time of their first chemotherapy course patients were randomized to receive either MPN 375 mg or MCP 1 mg/kg both administered in 3 equal doses, IV just prior to chemotherapy and then IM 6 and 12 hours after treatment. Patients receiving MPN experienced significantly less nausea (p less than 0.0005) and vomiting (p less than 0.0005) and antiemetic protection was maintained in patients receiving multiple chemotherapy courses. Complete protection (0 emesis) was observed in 58% of patients receiving MPN as compared with 20% of patients treated with MCP (p less than 0.005). The most frequent side effects were facial flush in 38% of patients and somnolence in 15% of patients receiving MPN and MCP, respectively. Complete protection from CMF-induced gastrointestinal side effects was observed in two-thirds of our patients receiving antiemetic MPN treatment. In these patients administration of the maximum cumulative CMF dose was possible without impairing their quality of life. MPN, at the dose and schedule reported, is an affective antiemetic drug suitable for use in breast cancer outpatients receiving adjuvant CMF therapy.     

Refractory vomiting with cisplatin therapy. Prospective study with the serotonin receptor antagonist GR 38032F

Emesis in chemotherapy containing Cisplatinum (DDP) is still a therapeutical dilemma. Emesis and nausea cause the cessation of a potential curative therapy in up to 10% of patients treated with DDP. We studied the antiemetic effectiveness of the selective Serotonin (5HT3)-receptor-antagonist Ondansetron (GR 38032F, Glaxo) in patients receiving high dose platinum chemotherapy. All patients suffered from severe emesis and were refractory to any standard antiemetic regimen (Metoclopramid). We studied the efficacy of the new drug against acute and delayed emesis following platinum chemotherapy. All adverse events are listed. Thirty four courses (n = 17 patients) of a platinum-containing regimen were analyzed so far. A sufficient antiemetic efficacy was observed in 56% of the courses. In 32 of 34 course (94%) the patients preferred the new drug compared with the standard antiemetic regime (Metoclopramid). In most cases only minor adverse events--which do not require any medical therapy--occurred. The most common adverse events were headache, constipation, dry mouth, abdominal discomfort and elevation of liver enzyme level without any clinical symptoms. One patient needed bowel surgery for severe constipation based on widespread intra-abdominal carcinosis.     

Oral ondansetron (GR 38032F) for the control of CMF-induced emesis in the outpatient

Summary The efficacy of the serotonin antagonist ondansetron (GR 38032F) was evaluated in the prevention of nausea and vomiting induced by CMF chemotherapy in 29 breast cancer patients. At their first treatment course of CMF, all given IV on day 1 q 21 days, patients were given oral antiemetic treatment as follows: ondansetron 8 mg, 2 h prior to CMF, repeated after 5 and 10 h the day of chemotherapy and then 8 mg tds for a minimum of 3 days to a maximum of 5 days following chemotherapy. At first course of CMF, complete protection from emesis and nausea was observed in 86.2% and 62% of patients, respectively. At subsequent CMF courses with ondansetron, complete control of emesis was observed in 80% of patients. Side effects were mild and no dystonic reactions were observed. Ondansetron represents an effective, safe, and easily administered outpatient regimen. The addition of a corticosteroid to ondansetron could further improve control of CMF-induced emesis.