Control of high-dose-cisplatin-induced emesis with an all-oral three-drug antiemetic regimen

 In this pilot trial, the antiemetic efficacy and tolerability of an all-oral antiemetic combination in the prevention of both acute and delayed nausea and vomiting following high-dose cisplatin was evaluated. Fifty-two patients receiving cisplatin (median dose 100 mg/m²) were entered. Patients received (1) 60 min prior to cisplatin: prochlorperazine spansule 15 mg, dexamethasone 20 mg, granisetron 2 mg; (2) 12 h after cisplatin: prochlorperazine spansule 15 mg, dexamethasone 10 mg; (3) on days 2 and 3: prochlorperazine spansule 15 mg b.i.d., dexamethasone 8 mg b.i.d.; (4) on days 4 and 5: dexamethasone 4 mg b.i.d. All antiemetics were administered orally. The study period was the 120 h after cisplatin administration. The primary efficacy end-point was complete control (no vomiting, retching or antiemetic rescue) of delayed emesis (24–120 h after cisplatin). Complete control of delayed emesis was achieved in 26 patients (53%). Nineteen patients (39%) noted no delayed nausea. Complete control of acute emesis (24 h after cisplatin) was attained in 44 patients (86%). The no nausea rate during the first 24 h was 74%. Overall, 39 patients (80%) were satisfied or very satisfied with their outcome. Treatment was well tolerated with infrequent and minor adverse events. In conclusion, an all-oral combination of granisetron, dexamethasone and prochlorperazine is a highly effective and well-tolerated regimen for preventing acute cisplatin-induced emesis. Control of delayed emesis was not better than with current standard treatment, and more effective approaches are needed. Published online: 19 August 1999     

Randomized, double-blind comparison of granisetron versus granisetron plus prednisolone as antiemetic prophylaxis during multiple-day cisplatin-based chemotherapy

 Ninety chemotherapy-naive cancer patients receiving cisplatin-based (≥50 mg/m²) chemotherapy participated in a randomized, double-blind, cross-over study comparing the safety and efficacy of granisetron (GRA) versus granisetron plus prednisolone (GRA+PRE). All patients received i.v. granisetron 3 mg and were randomly allocated to oral prednisolone 50 mg or placebo prior to chemotherapy. At the subsequent cycle of chemotherapy, patients were crossed over to the other antiemetic treatment. A complete response, defined as no eme- tic episodes and no worse than mild nausea, was obtained in 63% in the GRA group and in 79% of the patients in the GRA+PRE group day 1 (P=0.013). Complete response rates on days 1–3 were 16% vs 27% (P=0.251). Significantly less nausea and vomiting was seen with the combination in the first 24 h after cisplatin (P=0.001 and P=0.0003) and during days 1–3 (P=0.005 and 0.044). Patient preference was 51.5% for the combination and 26.5% for granisetron alone, whereas 22% had no preference (P=0.0270). Adverse reactions were mild and comparable; headache and constipation were the ones most frequently reported. Prednisolone significantly improves the antiemetic effect of granisetron in patients receiving cisplatin-based chemotherapy, but the study also emphasizes the poor complete protection rate in patients receiving multiple-day cisplatin-based chemotherapy.     

Unproven methods in cancer: a worldwide problem

 Questionable or unproven methods are used by cancer patients throughout the world. Treatments include drugs, vitamins, herbs, diets, healing, "psychological" treatments, folk medicines, and homeopathy. The exact frequency of questionable methods in cancer is difficult to evaluate because of the variety of methods, some being used as complementary treatments to conventional ones (and often not mentioned by patients) and others, as curative treatment (alternative treatment). In Europe, data are available for the Nordic countries, Switzerland, Germany, Austria, United Kingdom, The Netherlands, France and Italy. High frequencies of use are observed in German-speaking countries (52–65%). In North America, many publications give frequencies of between 7% and 54%. In Mexico, the frequency is 50%, higher than in Argentina (17%). In Australia, 22% have used complementary medicines. In Asia, some data are available from India, Taiwan and Japan. In Tunisia (northern Africa), the results of 59 interviews also show the use of questionable methods among Arabic patients. There is a lack of data from countries in Africa and in Asia. While some products are used all over the world (e.g. mistletoe, vitamins), others are country specific (Moerman diet in The Netherlands). Some traditional medicines are also country specific (e.g., Chinese medicine, Ayurvedic medicine in India). Both alternative and complementary unproven methods are prescribed either according to classical concepts of cancer treatment or according to a new concept of the world and of life. Published online: 22 July 1999     

Prevention of cisplatin-induced delayed emesis: still unsatisfactory

 The incidence of and prognostic factors in cisplatin-induced delayed emesis were evaluated in 522 naive cancer patients. They each received an intravenous combination of ondansetron and one of four different doses of dexamethasone for the prevention of acute emesis and a combination of orally administered metoclopramide plus intramuscular dexamethasone for the prevention of delayed emesis. Despite the best prophylaxis for acute and delayed emesis, 37.4% / 57.1% of patients experienced delayed vomiting / nausea. The presence of acute vomiting / nausea was the main prognostic factor in delayed vomiting / nausea; therefore, a multifactorial analysis of the results achieved during the delayed phase adjusted for those obtained during the acute phase should be carried out in every study evaluating the efficacy of different antiemetic drugs for delayed emesis. Published online: 9 September 1999     

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.     

Delayed emesis: a dilemma in antiemetic control

Delayed emesis remains a major factor limiting successful antiemetic treatment. It is well described in patients receiving cisplatin at doses of 100 mg/m² or greater (occurring in nearly 90% of patients), but its incidence and severity in other settings is less well known. Several studies have indicated that combinations of oral metoclopramide plus dexamethasone can decrease the incidence of this problem by one-half; however, a large number of patients remain for whom delayed emesis is their main emetic problem. To date, studies with single-agent serotonin antagonists have not shown encouraging efficacy. In addition, it appears that delayed emesis may begin as early as 16 h after chemotherapy, yielding implications for new study designs. Proper methodology for clinical studies has been demonstrated in a few well-conducted trials, which should form a basis for future research.Presented as an invited lecture at the 4th International Symposium: Supportive Care in Cancer, St. Gallen, Switzerland, 24–27 February 1993     

Controversies in new antibiotic therapy for ambulatory patients

 The care of the febrile neutropenic patient has undergone a shift in the last 10 years with the realization that neutropenic patients presenting with fever do not constitute a homogeneous group. Strategies of risk assessment have allowed the testing of novel therapies including oupatient treatment with oral and intravenous antibiotics, either in combination regimens or as monotherapy; the addition of growth factors to hasten the return of the absolute neutrophil count; and the possibility of self-initiation of antibiotics by cancer patients when they develop fever. The clinical trials data regarding these new approaches will be reviewed, and areas requiring further research will be discussed.     

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.     

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     

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.     

Fatigue in patients with cancer: results with National Cancer Institute of Canada Clinical Trials Group studies employing the EORTC QLQ-C30

 The purpose of this study was to examine the factors which affect the level of fatigue among patients participating in clinical trials in which this symptom had been assessed with the EORTC QLQ-C30. Data were assembled from 2390 patients in ten clinical trials in which the QLQ-C30 had been used to assess baseline and on-study quality of life. The relationship between the level of fatigue reported by the patients on the fatigue scale of this questionnaire and patient and disease characteristics was assessed in univariate and multivariate cross-sectional analyses. In addition, changes in fatigue scores were compared in a longitudinal analysis among patients on two arms of an anti-emetic trial whose emesis control was markedly different. Baseline fatigue levels differed substantially among patients taking part in the different trials. Factors associated with greater fatigue severity on univariate analysis included: female gender, presence of metastatic disease, and poorer performance status. In addition, on multivariate analyses the oldest patients were found to have less fatigue, as were patients with breast cancer, while patients with ovarian and lung cancer experienced greater fatigue. Patients on the arm of the anti-emetic trial in which emesis was better controlled showed significantly less increase in fatigue after receiving chemotherapy. The fatigue scale of the QLQ-C30 appears to provide a useful approach to assessing this important symptom. The relationships found between fatigue and patient and disease characteristics need further exploration as does the degree to which the QLQ-C30 fully captures this dimension of quality of life.     

A survey of mouth pain and dryness in patients with advanced cancer

 An 11-item face-to-face survey was conducted in 99 consecutive patients with advanced cancer to determine the prevalence, intensity, reporting and treatment, presumed cause(s), and importance of mouth pain and dryness. Sixteen of the 99 patients (16%) reported experiencing mouth pain at a mean intensity corresponding to 5.5±SD 2.21 on a 0 (no pain) to 10 (worst possible pain) numerical scale, and 88 (88%) patients reported dry mouth at a mean intensity corresponding to 6.2±SD 2.21. Nine (56%) of the 16 patients with mouth pain and 39 (44%) of the 88 patients with mouth dryness reported these symptoms to their attending physician(s). Sixty-nine percent (27/39) of patients who reported having a dry mouth were advised by their physician(s) to pursue one or more treatments. The most common treatments recommended (and frequencies) were drinking water/taking sips of fluid (13), gargling with bicarbonate mouthwash (4), using an artificial saliva spray (4), and using an oral fungal suspension for thrush (4). The most common findings on oral examination included: possible thrush (53 patients), upper and lower dentures (33 patients), and multiple dental restorations (23 patients). The causes most frequently assumed to be responsible were ill-fitting dentures for mouth pain, and medications and possible oral fungal infections for mouth dryness. The mean values given for the importance of the symptoms of mouth pain and dryness relative to other symptoms or problems experienced by the patients were 4.4±SD 1.84 and 3.6±SD 1.67, respectively, on a Likert scale ranging from 1 (not important) to 7 (great importance). Mouth dryness was more frequently reported than mouth pain. The mean rating for the intensity of mouth pain was higher than that for mouth dryness, although both were of moderate importance to patients relative to other symptoms or problems experienced at the time. Patients tended to underreport mouth pain and dryness, and physicians tended to address such complaints inadequately. Published online: 3 August 2000     

Neuropharmacology of emesis and its relevance to anti-emetic therapy

 Recent great advances in the neuropharmacology of the emetic pathways have led to better therapy and improved insight into pathophysiological processes in patients undergoing chemo- and radiotherapy. This article gives an overview of the area, outlines current controversies and makes recommendations for future clinical studies.     

A model of palliative care: the palliative medicine program of the Cleveland Clinic Foundation

 Patients with advanced diseases, both cancer and noncancer, experience high symptom prevalence and psychosocial distress. Multiple unmet needs in the physical, psychosocial and spiritual domains are common. In the United States, palliative medicine is an emerging discipline that focuses on meeting these needs to achieve optimal quality of life for the patient–family unit. The majority of palliative care programs in the U.S. are consultation based. In contrast, the Palliative Medicine Program of the Cleveland Clinic Foundation offers multidisciplinary, comprehensive care from a primary or a consultative focus. The program has clinical, research, and educational components. Established as a consultation service in 1987, the clinical component now includes inpatient and outpatient consultation services, a dedicated acute care inpatient hospital unit, outpatient palliative medicine and cancer pain clinics, palliative home care, hospice home care and hospice residential care. Over 800 new patient consultations took place in 1997. In this paper, development of the program and its structure are described. Challenges to effective communication in a large program within a tertiary care institution are discussed, and strategies designed to meet these challenges are presented. Published online: 29 May 2000     

Prospective study on fungemia in children with cancer: analysis of 35 cases and comparison with 130 fungemias in adults

 The aim of this prospective study on fungemia in children with cancer compared with adults with cancer appearing during the last 10 years in a pediatric hospital and in national cancer institutions was to investigate risk factors, etiology, therapy, complications and outcome. Univariate analysis showed significant differences in 35 children with cancer and fungemia in comparison with 130 cases of fungemias in adults with cancer. It was found that (1) therapy with corticosteroids (40 vs 18.5%, P<0.03), (2) breakthrough fungemia during ketoconazole prophylaxis (20 vs 7.7%, P<0.025), and (3) meningitis as a complication of fungemia (11.4 vs 0.8%, P<0.001) occurred more frequently in the pediatric subgroup with fungemia. Candida albicans was more common as the causative agent of fungemia among adults (58.5 vs 37.1, P<0.02) than in children. However, mortality was similar in children with cancer and in adults with cancer and fungemia (31.4 vs 23.1%, NS). Comparison of risk factors revealed no differences between adults and children with cancer and fungemia except in etiology, breakthrough fungemia during prophylaxis with ketoconazole, prior therapy with corticosteroids and meningitis as a complication. The outcome was also similar in pediatric and adult cancer patients with fungal bloodstream infection. Published online: 31 March 2000     

Prevalence and severity of symptoms in terminal cancer patients: a study in Taiwan

 This paper reports a prospective study conducted between September 1997 and July 1998 in 232 consecutive patients with terminal cancer. A structured data collection form was used daily to evaluate symptoms, which were analyzed at the time of admission, 1 week after admission and 48 h before death. Terminal cancer patients in this study were polysymptomatic. There were no statistically significant differences in the prevalence of most symptoms with the primary site of cancer. The majority of symptoms improved at the end of the 1st week after admission, but many symptoms worsened just before death. The high prevalence of symptoms and lack of significant difference among primary tumor sites may be related to shorter survival times caused by late referral, which is common in Taiwan. Published online: 17 January 2000     

Building an intercultural nursing terminology bank for the phenomenon, Violence, of the International Classification of Nursing Practice®: a methodological perspective

The aim of this article was to present the methodology and results of an investigation into the intercultural evolution of the nursing phenomenon--Violence--from the identification phase to the summative evaluation phase, in order to contribute to the evolution of the International Classification of Nursing Practice (ICNP). The organizing construct was concept analysis of a nursing phenomenon. The identification of a universal problem in psychiatric-mental health nursing by a team of 10 international leaders in the speciality led from the phase of concept analysis to development of a postgraduate educational module. The results of the original analysis of the concept and findings from clinical and evaluation data resulted in further analysis and consequent synthesis of the concept. Results will be disseminated to the International Council of Nursing (ICN) for the International Classification of Nursing Practice (ICNP) to further the evolution of the phenomenon from a focus on the individual to that of the aggregate (social violence). The methodology pointed to a lack of transfer in the phenomenon from a focus on the individual to that of aggregates in the ICNP. There was also a paucity of intercultural components. The phenomena of Abuse and Aggression appear to have been used synonymously with Violence, without an explanation. The data, and the methods used for its collection and submission, will enhance the ICNP.