A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-induced emesis

Goals of work Comparing antiemetic efficacy of different 5-HT₃-receptor antagonists (5-HT₃RAs) is difficult due to inter-study variability. Therefore, a meta-analysis was performed to comparatively evaluate dolasetron, granisetron, ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting (CINV). Patients and methods Comparisons between 5-HT₃RAs were based on 44 randomized studies (including 12,343 patients) identified by MEDLINE, CANCERLIT or EMBASE searches and subcategorized by chemotherapy type (cisplatin- or non-cisplatin-based). Main results When all studies were combined, granisetron was equivalent to ondansetron (n = 27), and showed an advantage vs tropisetron (p = 0.018; n = 12). Ondansetron vs tropisetron (n = 11) and ondansetron vs dolasetron (n = 3) revealed equivalence in each comparison. An advantage for 3 mg granisetron vs 8 mg ondansetron was found in non-cisplatin-based studies (p = 0.015; n = 6). Overall equivalence was seen between ondansetron, 24 or 32 mg, and granisetron, 2 or 3 mg, for all studies (n = 13). There was a possible advantage for higher (24 or 32 mg) vs lower (8 mg) ondansetron dose regimens with cisplatin-based trials (n = 6). No differences were seen between 3 and 1 mg granisetron doses (n = 6). Conclusions Efficacy of 5-HT₃RAs for preventing CINV following cisplatin- and non-cisplatin-based chemotherapy is comparable, with the exception of granisetron vs tropisetron. Some differences were noted in dosing subanalyses. The study has been presented in part at ASCO 5–8 June 2004, New Orleans, USA.     

Chemotherapy-induced dermatological toxicity: frequencies and impact on quality of life in women’s cancers. Results of a prospective study

Purpose The study aimed to determine the prevalence of dermatological side effects and its impact on quality of life in patients receiving systemic chemotherapy for women’s cancers. Materials and methods A prospective study was conducted on patients with histologically confirmed advanced women’s cancers who were deemed candidates for adjuvant or palliative chemotherapy. Patients were systemically examined for skin, hair, and nail side effects. The impact of those side effects on their quality of life was assessed using the health-related quality of life score (HRQL). Results Between April 2001 and October 2001, 91 patients received 1 to 17 (median 4) courses of chemotherapy. Malignancies included breast cancer (n = 39, 43%), ovarian cancer (n = 32, 35%), cervical cancer (n = 12, 13%), endometrial cancer (n = 5, 6%), fallopian tube cancer (n = 2, 2%), and vaginal cancer (n = 1, 1%). Chemotherapy agents included taxanes (n = 42, 46%), PEG doxorubicin (n = 17, 7%), other anthracyclines (epirubicin and doxorubicin; n = 6, 19%), topotecan (n = 13, 14%), and other agents (n = 13, 14%). Overall incidence of skin, nail, and hair side effects was 86.8% (n = 79). Seventeen patients (18.7%) developed a palmo-plantar erythrodysesthesia (PPE), and nine of those (53%) were of grade 3 in common toxicity criteria scale (NCI). Twenty-one patients (23.1%) developed nail changes such as subungual hematomas, onycholysis, and leukonychias or nail loss, while 69 (75.8%) developed hair loss. There was a higher incidence of PPE in patients receiving chemotherapy for palliation rather than cure (percent over percent, p < 0.001, Fisher’s exact test). Using the HRQL score, skin changes were the most frequently reported unpleasant side effect (34.1%), and of those patients who developed PPE, this was reported by n = 8 (47%) as the most unpleasant. Conclusions Dermatological chemotherapy side effects are frequent after treatment of women’s cancers and have a major impact on quality of life as assessed by HRQL. Counseling of patients with women’s cancers and the profile of side effects of chemotherapeutic agents should be considered before considering an adjuvant or palliative chemotherapy regimen.     

Physical activity correlates and barriers in head and neck cancer patients

Purpose Our study purpose was to determine physical activity correlates and barriers among head and neck cancer patients. Materials and methods Fifty-nine (response rate = 91%) head and neck cancer patients from an academic oncology clinic enrolled in a cross-sectional study utilizing chart review and self-administered questionnaire. Results The majority were men (83%) and white (92%) with mean age of 58 ± 12.8 years and mean months since diagnosis of 18.6 ± 51.9. The strongest bivariate correlates of physical activity included enjoyment (r = 0.41; p = 0.002), symptom index (r = −0.36; p = 0.006), alcohol use (r = 0.36; p = 0.007), task self-efficacy (r = 0.33; p = 0.013), perceived barriers (r = −0.27; p = 0.047), and comorbidity score (r = −0.27; p = 0.042). Stepwise regression demonstrated independent associations with physical activity for enjoyment (β = 0.38; p = 0.002) and symptom index (β = −0.33; p = 0.006; R ² = 0.28). The most prevalent barriers significantly associated with physical activity included dry mouth or throat (r = −0.32; p = 0.016), fatigue (r = −0.27; p = 0.043), drainage in mouth or throat (r = −0.41; p = 0.002), difficulty eating (r = −0.32; p = 0.015), shortness of breath (r = −0.30; p = 0.024), and muscle weakness (r = −0.29; p = 0.033). Conclusions Our results showed that the strongest independent correlates of physical activity were social cognitive (i.e., enjoyment) and treatment-related (i.e., symptom index). Treatment-related activity barriers were frequent and significantly associated with reduced activity. Efforts to enhance exercise adherence in head and neck cancer patients should focus on optimizing enjoyment and managing treatment-related barriers.     

Segmental high intensity on T1-weighted hepatic MR images

Background We investigated the diagnostic importance of segmental high-intensity (SHI) areas not corresponding to mass lesions on T1-weighted magnetic resonance (MR) images. Methods We conducted a retrospective investigation of hepatic MR images obtained from 634 patients during a 4-year period at our institution. Images were compared with findings reported in the patients’ medical records. There were 16 patients (2.5%) with SHI areas not corresponding to a mass lesion. We compared MR images with plain computed tomographic (CT) scans (n = 16), angiograms (n = 12), and histologic findings (n = 10). Results The segments with intrahepatic bile duct dilatation showed hyperintensity on T1-weighted images. In six of 16 patients, the biliary duct was more dilated in the area of hyperintensity than in areas without hyperintensity. The SHI areas appeared as areas of low attenuation (n = 13), high attenuation (n = 1), or isoattenuation (n = 2) on plain CT scans. Histologically, these areas showed ductular proliferation and deposition of bile pigment within the hepatocytes. Conclusion Segmental areas of increased signal intensity on T1-weighted images were probably due to intrahepatic cholestasis.     

Efficacy and safety of different doses of granisetron for the prophylaxis of cisplatin-induced emesis

The purpose of this study was to evaluate the efficacy and safety of four different doses of granisetron when administered as a single intravenous (i.v.) dose for prophylaxis of cisplatin-induced emesis in a multicenter, randomized, parallel-group, double-blind investigation. A total of 353 chemotherapy-naive patients were enrolled, stratified according to cisplatin dose (moderate dose: 50–80 mg/m²,n = 169; high dose: 81–120 mg/m²,n = 184) and randomized to one of four granisetron doses: 5, 10, 20, or 40 µ/kg. Control of emesis was evaluated by the percentages of patients attainingcomplete response (no vomiting or retching, and no rescue medication) andmajor response (2 episodes of vomiting or retching, and no rescue medication). Patients were assessed on an inpatient basis for 18–24 h. Safety analyses consisted of adverse events and laboratory parameter changes. Complete response rates over 24 h after chemotherapy were 23%, 48%, 48%, and 44% for granisetron doses of 5, 10, 20, and 40 µg/kg, respectively, in the combined patient population (P=0.011 for linear trend); 29%, 56%, 58%, and 41%, respectively, in the moderate-dose cisplatin stratum (P=0.278 for linear trend); and 18%, 41%, 40%, and 47%, respectively, in the high-dose cisplatin stratum (P = 0.011 for linear trend). Transient headache was the most frequently reported adverse event (19%). There was no evidence of association between increased dose and headache. A single 10-, 20- or 40-µg/kg dose of granisetron is comparably effective in controlling nausea and vomiting associated with moderateor high-dose cisplatin chemotherapy. Granisetron was safe and well tolerated at all doses.     

Needs of developing the skills of palliative care at the oncology ward

Background To clarify the prevalence and severity of the symptoms, 203 consecutive patients with breast, prostate and other cancers treated mainly for palliation were surveyed. Materials and methods The series includes 116 men and 87 women with the mean age of 65 years (range 27–86 years). The patients filled-up the Edmonton Symptom Assessment System (ESAS) questionnaire with 11 items describing cancer-related symptoms in the visual analogue scale (VAS). Results Altogether, 98% of the patients reported at least 1 of the 10 symptoms. There was a significant difference in the score frequencies between the 10 symptoms (p = 0.0001), fatigue receiving the highest frequency (50.8%) of the high scores. Fatigue was also the single most frequent symptom reported by 86.3% of the patients, followed by pain at effort (71.5%), sleeplessness (71.1%) and depression (59.0%). The most disturbing syndrome was pain (n = 48, 23.9%), followed by fatigue (n = 28, 13.9%), depression (9.5%) and dyspnoea (6.0%). Altogether, 75% had more than 5 symptoms and 10% reported all 10 symptoms. The total number of symptoms was not significantly associated with sex (p = 0.781) or age (p = 0.062), but it was associated with the diagnostic group; patients with breast cancer (n = 41) and those with prostate cancer (n = 44) reported fewer symptoms than the patients with other cancers (n = 116)(p = 0.023, Kruskal–Wallis). Conclusions Symptoms related to cancer are common among patients treated with palliative indication, but if not specifically surveyed, may remain un-detected and un-treated. ESAS as a clinical tool brings more symptoms to the attention of the physicians and helps in getting a comprehensive insight into the patient’s problems.     

Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies

Goals of the work To assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes in patients with hematologic malignancies receiving allogeneic hematopoietic stem-cell transplantation (HSCT). Materials and methods A retrospective chart review study of 281 allogeneic HSCT recipients with hematologic malignancies was undertaken at a single academic center. OM extent and severity were assessed across eight oropharyngeal sites using a validated scale, which was scored as follows: no erythema/ulceration=0; erythema only=I; ulceration, one site=II; ulceration, two sites=III; ulceration, three sites=IV and ulceration, four or more sites=V. OM assessments began on the day of conditioning and continued twice weekly within 28 days or hospital discharge. Analyses examined the relationship between the worst OM grade and selected adverse outcomes, including days with fever, days of total parenteral nutrition (TPN), days of parenteral narcotic therapy, incidence of significant (common terminology criteria (CTC) grade 3 or 4) infection, mortality and inpatient days and charges. Main results The mean age of the study subjects was 41 years. Of the patients, 96% (n = 269) received total body irradiation and 76% (n = 214) experienced an OM grade of ≥II (i.e., ulceration). The worst OM grade was significantly (p < 0.05) associated with the number of days of TPN and parenteral narcotic therapy, number of days with fever, incidence of significant infection, time in hospital and total inpatient charges. Conclusions OM is associated with worse clinical and economic outcomes in patients with hematologic malignancies undergoing allogeneic HSCT.     

A patient-reported outcome instrument to assess the impact of oropharyngeal mucositis on health-related quality of life: a longitudinal psychometric evaluation

Goals of work  An oropharyngeal mucositis (OM)-specific health-related quality of life measure (OMQoL) has been developed to assess the impact of OM from the perspective of patients. The current paper describes the convergent, concurrent, and known-group validities and responsiveness in relation to clinical and health outcomes. Materials and methods  A multicenter approach was used, and 137 patients treated with different cancer therapies completed the OMQoL and the European Organization for Research and Treatment of Cancer Quality of Life questionnaire [EORTC QLQ-C30 (Ch)] twice over a 4-week period or weekly over a 7-week period, along with concurrent measures of OM and its related symptoms. Main results  The OM-related symptom scores correlated highly with the OMQoL, confirming its convergent validity (r = −0.724–−0.971, p < 0.01). Moderate correlations between the subscales of the OMQoL and EORTC QLQ-C30 (Ch) were indicative of good concurrent validity (r = 0.450–0.724, p < 0.01). The OMQoL was able to distinguish between patients with different severities of OM (p < 0.01) and types of cancer therapy (p < 0.01), providing evidence of good known-group validity. The changes in effects sizes corresponding to changes in OM curves indicate that the OMQoL is responsive to changes in OM status. Conclusions  These findings suggest that the OMQoL has very good psychometric properties and can be used as a health-related quality of life assessment for cancer patients with OM. Much work is still needed in strengthening the psychometric qualities and interpretability of the OMQoL by demonstrating its ability to detect outcome changes over time.     

Statistical analysis of the adverse effects of glycopeptide antibiotics, based on pharmacokinetics and toxicokinetics (PK/TK)

The effects of vancomycin hydrochloride (VCM) and teicoplanin complex (TEIC) on hepatic function and renal function were evaluated in rats. VCM was injected via the jugular vein at doses of 40, 100, and 250 mg/kg, and TEIC was injected via the jugular vein at doses of 10, 30, 40, 50, and 60 mg/kg, both after being dissolved in 1 ml of saline solution. Increased doses of VCM significantly increased the integrated plasma concentrations, from 0 to 8 h, for blood urea nitrogen (BUN_0–8) and serum creatinine (SCr_0–8). TEIC gave rise to a slight increase in both BUN_0–8 and SCr_0–8 as its dose was increased. On the other hand, TEIC significantly increased the integrated plasma concentrations, from 0 to 8 h, for aspartate aminotransferase (AST_0–8), and alanine aminotransferase (ALT_0–8), at doses from 40 mg/kg to 60 mg/kg, though VCM did not increase these concentrations. This study suggests the importance of paying attention to hepatic function – in addition to renal function – when TEIC is administered to patients with methicillin-resistant Staphylococcus aureus (MRSA).     

Safety of ondansetron loading doses in children with cancer

Introduction In highly emetogenic chemotherapy, the recommended dose of the serotonin-receptor antagonist ondansetron (5 mg/m² q8h) may be insufficient to prevent chemotherapy-induced nausea and vomiting. In adults, ondansetron-loading doses (OLD) of 32 mg are safe. We aimed to evaluate in children the safety of an OLD of 16 mg/m² (top, 24 mg) i.v., followed by two doses of 5 mg/m² q8h. Materials and methods This retrospective single-center study included all pediatric oncology patients having received ≥1 OLD between 2002 and 2005. Adverse events (AE) definitely, probably, or possibly related to OLD were studied, excluding AE not or unlikely related to the OLD. Associations between potential predictors and at least moderate AE were analyzed by mixed logistic regression. Results Of 167 patients treated with chemotherapy, 37 (22%) received 543 OLD. The most common AE were hypotension, fatigue, injection site reaction, headache, hot flashes/flushes, and dizziness. At least mild AE were described in 139 OLD (26%), at least moderate AE in 23 (4.2%), and severe AE in 5 (0.9%; exact 95% confidence interval [CI], 0.4–2.1). Life-threatening or lethal AE were not observed (0.0%; 0.0–0.6). At least moderate AE were significantly more frequent in female patients (odds ratio [OR] 3.5; 95% CI 1.4–8.8; p = 0.010), after erroneously given second OLD (17.0; 1.9–154; p = 0.012) and higher 24 h cumulative surface corrected dose (1.26 per mg/m²; 1.06–1.51; p = 0.009). OLD given to infants below 2 years were not associated with more frequent AE. Conclusions Ondansetron-loading doses of 16 mg/m² (top, 24 mg) i.v. seem to be safe in infants, children, and adolescents. Results presented in part at the 20th Symposium of the Multinational Association of Supportive Care in Cancer, St. Gallen, Switzerland, June 27–30, 2007.     

The impact of an educational DVD on cancer patients considering participation in a phase I clinical trial

Goals of work The quality of informed consent in phase I trials is controversial, partially due to gaps in patient understanding. We assessed an educational DVD’s impact on knowledge and satisfaction in cancer patients newly referred to a phase I clinic. Materials and methods Forty-nine patients were randomly assigned to view an educational DVD (n = 22) which explained phase I trials or a placebo DVD (n = 27). Patients completed a questionnaire assessing knowledge of phase I studies and satisfaction with the DVD. The blinded interviewing physician (n = 8) rated the patient’s understanding of phase I trials. Main results The mean patient age was 56; 61% were male. Patients who viewed the educational DVD were less likely to believe that phase I trials determine drug efficacy (p = 0.019), more likely to know that phase I drugs have not been thoroughly studied in humans (p = 0.003), and less likely to believe that these agents have proven activity against human cancers (p = 0.008). More patients who viewed the educational DVD agreed/strongly agreed that the DVD provided useful information (p < 0.001), were confident in their knowledge of phase I trials (p = 0.031), felt aided in their decision to enter a phase I study (p = 0.011), and would have more questions for their physicians because of the DVD (p = 0.017). No statistically significant difference in physician perception of patient understanding or phase I trial accrual was observed between the educational and placebo DVD groups. Conclusions An educational DVD increased patient knowledge and satisfaction regarding participation in phase I clinical trials.     

Barriers to referral to inpatient palliative care units in Japan: a qualitative survey with content analysis

Objectives We investigated the barriers to referral to inpatient palliative care units (PCUs) through a qualitative study across various sources of information, including terminal cancer patients, their families, physicians, and nurses. Materials and methods There were 63 participants, including 13 advanced cancer patients, 10 family members, 20 physicians, and 20 nurses in palliative care and acute care cancer settings from five regional cancer institutes in Japan. Semi-structured interviews were conducted regarding barriers to referral to PCU, and data were analyzed by content analysis method. Results A total of 21 barriers were identified by content analysis. The leading barriers were (1) a negative image of PCUs by patients and families (n = 39), (2) delay of termination of anti-cancer treatment by physicians in the general wards (n = 24), (3) unwillingness to end anti-cancer treatment and denial of the fatal nature of the disease by patients and families (n = 22), (4) patient’s wish to receive care from familiar physicians and nurses (n = 20), and (5) insufficient knowledge of PCUs by medical staff in general wards (n = 17). Conclusions To correct these unfavorable images and misconceptions of PCUs, it is important to eliminate the negative image of PCUs from the general population, patients, families, and medical staffs. In addition, early introduction of palliative care options to patients and communication skills training regarding breaking bad news are relevant issues for a smooth transition from anti-cancer treatment to palliative care.     

Comparing pain control and ability to eat and drink with standard therapy vs Gelclair: a preliminary,double centre,randomised controlled trial on patients with radiotherapy-induced oral mucositis

Goal of the work Oral mucositis (OM) is a functionally destructive complication of aggressive head and neck cancer therapy, often resulting in intense pain, an inability to eat and drink and secondary malnutrition and dehydration. The barrier-forming properties of Gelclair have shown promise in relieving such symptoms. The aim of this randomised-controlled trial was to evaluate the efficacy of Gelclair, as compared to standard therapy, as a means of short-term symptom control for patients suffering from radiotherapy-induced OM. Materials and methods Twenty patients, with radiotherapy-induced OM seen in two oncology centres in Devon, were randomised to either standard therapy (Sucralfate and Mucaine) or Gelclair and assessed over 24 h. Both treatments were taken four times during the 24-h period, 30 min before meals. Main results No significant difference was found between the Gelclair and standard therapy arms in terms of general pain (F = 1.512, df = 1, 17, ns). There did appear to be a trend towards pain improvement initially after the use of Gelclair, but this did not last for the full 24-h assessment period. There was no significant reduction in pain on speaking (F = 0.261, df = 1, 17, ns) nor an improvement in capacity to eat and drink, although the effects of standard therapy did appear to last longer than the Gelclair. Conclusion This study indicates that Gelclair is no more effective than current standard practice in relieving the pain associated with radiotherapy-induced OM. Nevertheless, observations from this preliminary study warrant further investigation, with a view to shaping the way forward for head and neck cancer practice on a national level.     

Associations between quality of life, fatigue, and cytokine levels in patients aged 50+ with acute myeloid leukemia

Goals of work  Quality of life (QOL) is significantly impaired in patients with acute myeloid leukemia (AML), and fatigue is the most common and disabling symptom; effective treatment measures have yet to be found. Cytokines, biomarkers of inflammation, may moderate both health outcomes, but published data are limited. We looked at the role of cytokines in modulating QOL and fatigue in an older AML population. Patients and methods  We recruited 34 English-speaking patients (23 men, 11 women) aged 50 or older with AML within 1 year of diagnosis. QOL and fatigue were assessed with validated questionnaires. Blood was simultaneously drawn for quantitative measurement of a 13-cytokine panel. Repeat measurements were done 4–6 weeks later (n = 28 patients). Spearman correlations between health measures and cytokine levels were examined at baseline, as were changes in variables between time points. A potentially clinically important correlation was defined as an r ≥ 0.30. Results  At baseline, potentially clinically important correlations were noted between global QOL and interferon (IFN)-γ (r = −0.376, p = 0.031), interleukin (IL)-2 (r = −0.340, p = 0.053), IL-5 (r = −0.368, p = 0.035), IL-8 (r = −0.312, p = 0.077), and TNF-α (r = −0.326, p = 0.064). A similar correlation was observed between IL-6 and fatigue (r = 0.332, p = 0.059). Between time points, there were no potentially important correlations between changes in global QOL and any cytokine. However, potentially important correlations with fatigue were seen with both IL-5 (r = 0.344, p = 0.073) and IL-10 (r = 0.326, p = 0.091) between time points. Conclusions  These preliminary data provide support for a larger controlled study of cytokines, fatigue, and QOL in patients with AML.     

A non-randomized comparison of mindfulness-based stress reduction and healing arts programs for facilitating post-traumatic growth and spirituality in cancer outpatients

Goals of work The aim of this study was to compare a mindfulness-based stress reduction (MBSR) program and a healing through the creative arts (HA) program on measures of post-traumatic growth (PTGI-R), spirituality (FACIT-Sp), stress (SOSI), and mood disturbance (POMS) in cancer patients. Materials and methods A sample of cancer outpatients (MBSR, n = 60; HA, n = 44) with a variety of diagnoses chose to attend either an 8-week MBSR program or a 6-week HA program and were assessed pre- and post-intervention. The majority of participants were female, married, and had breast cancer. Main results Repeated measures analysis of variance indicated that participants in both groups improved significantly over time on overall post-traumatic growth (p = 0.015). Participants in the MBSR group improved on measures of spirituality more than those in the HA group (p = 0.029). Participants in the MBSR group also showed more improvement than those in HA on measures of anxiety (POMS, p = 0.038), anger (POMS, p = 0.004), overall stress symptoms (SOSI, p = 0.041), and mood disturbance (POMS, p = 0.023). Several main effects of time were also observed in both groups. These results were found despite attrition in both groups. Conclusions Both programs may improve facilitation of positive growth after traumatic life experiences for those who choose to participate. MBSR may be more helpful than HA in enhancing spirituality and reducing stress, depression, and anger.     

Comparison of octreotide and hyoscine butylbromide in controlling gastrointestinal symptoms due to malignant inoperable bowel obstruction

 In advanced cancer patients with inoperable bowel obstruction, the administration of antisecretive and antiemetic drugs has proved to be effective in controlling gastrointestinal symptoms caused by bowel obstruction. However, controlled studies concerning the most effective antisecretive drug are lacking. The aim of this randomized controlled study was to determine whether octreotide or hyoscine butylbromide was the more effective antisecretive drug for use in states of inoperable bowel obstruction. Eighteen patients with inoperable bowel obstruction randomly received octreotide 0.3 mg daily (n=9) or hyoscine butylbromide (HB) 60 mg daily (n=9) s.c. The following parameters were measured: episodes of vomiting, nausea, drowsiness, continuous and colicky pain, using a Likert scale corresponding to a numerical value: (none 0, slight 1, moderate 2, severe 3) recorded before starting the treatment (T0) and 24 h (T1), 48 h (T2) and 72 h after (T3), and the mean daily amounts of fluids administered i.v. or s.c. during the period of study. Three patients dropped out of the study because data were incomplete. Octreotide treatment induced a significantly rapid reduction in the number of daily episodes of vomiting and intensity of nausea compared with HB treatment at the different time intervals examined. No relevant changes were found in dry mouth, drowsiness and colicky pain. Lower levels of hydration were associated with nausea regardless of the treatment. At the doses used in this study, octreotide was more effective than HB in controlling gastrointestinal symptoms of bowel obstruction. Further studies are necessary to understand the role of hydration more clearly in such a clinical situation. Published online: 5 October 1999     

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.     

A double-blind, randomised, parallel study comparing intravenous dolasetron plus dexamethasone and intravenous dolasetron alone for the management of fractionated cisplatin-related nausea and vomiting

 Fractionated cisplatin-containing regimens are routinely used for chemotherapy in certain types of cancer. Dolasetron has been shown to be effective in preventing acute emesis related to high-dose cisplatin chemotherapy over 24 h; its effectiveness has not been evaluated in fractionated cisplatin-containing chemotherapy. This trial was designed to assess the efficacy of dolasetron alone or dolasetron plus dexamethasone in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. The patients were 210 cancer in-patients, who were randomised to receive 100 mg dolasetron i.v. or 100 mg dolasetron i.v. plus 20 mg dexamethasone before chemotherapy primarily with cisplatin (15–50 mg/m²) infused over ≤4 h for at least 2 but not more than 5 consecutive days. Dolasetron was administered to all patients 30 min before cisplatin. Dexamethasone was administered in double-blind fashion 5 min before cisplatin. Efficacy was measured at hour 24 of each study day using complete response (no vomiting and no rescue medication) and maximum severity of nausea, self-assessed by patients using a 100-mm visual analogue scale. Most (198) of the patients completed the study and were evaluable. Overall complete response rates were significantly higher in the dolasetron plus dexamethasone group than in the dolasetron only group (72.9% vs 40.8%, respectively; P<0.0001). Complete response rates on each study day were also significantly higher with dolasetron plus dexamethasone than with dolasetron alone (P<0.029), with an attenuated efficacy in the delayed phase in both groups. Chi-square test and logistic regression applied to daily response rates indicated a significant influence of treatment (day 1: P=0.0002, day 2: P<0.0001, day 3: P=0.0007, day 4: P=0. 0007, day 5: P=0.029). Treatment and duration of chemotherapy exerted the only statistically significant subgroup effects on complete response (P<0.0001). Both treatments were administered safely. As seen with other 5-HT₃ receptor antagonist antiemetics, the addition of dexamethasone to dolasetron significantly increases effectiveness in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. Both dolasetron and dolasetron plus dexamethasone were well tolerated. Published online: 19 August 1999