Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles

We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase.     

Control of emesis 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 followed 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.     

Analysis of radiation- and 5-FU-induced inhibition of cell proliferation by an automatic colony analyser

PURPOSE: To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). PATIENTS AND METHODS: A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better." For each category of change in the SSQ, the corresponding differences were calculated in QLQ-C30 mean scores and effect sizes were determined. RESULTS: For patients who indicated "no change" in the SSQ, the mean change in scores in the corresponding QLQ-C30 domains was not significantly different from 0. For patients who indicated "a little" change either for better or for worse, the mean change in scores was about 5 to 10; for "moderate" change, about 10 to 20; and for "very much" change, greater than 20. Effect sizes increased in concordance with increasing changes in SSQ ratings and QLQ-C30 scores. CONCLUSION: The significance of changes in QLQ-C30 scores can be interpreted in terms of small, moderate, or large changes in quality of life as reported by patients in the SSQ. The magnitude of these changes also can be used to calculate the sample sizes required to detect a specified change in clinical trials.     

A cross-validation of the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) for Japanese with lung cancer

The EORTC QLQ-C30 was developed in English-speaking cultures. To determine if this instrument could cross a broad cultural divide and be used in Japan, the cross-cultural validity of its Japanese version was estimated. In evaluating psychometric testing, internal consistency by Cronbach's alpha, item-discrimination by multitrait scaling analysis, and validity analysis with ECOG performance score (PS) and Karnofsky Performance Status Scale (KPS) were performed. The QLQ-C30 (version 1.0) was given to 105 patients with lung cancer. Although the response rate was low in patients with PS 4, the questionnaire was well accepted by patients with PS 0-3. The Japanese QLQ-C30 has a weak scale of role functioning in terms of item discriminative validity. It also has a weak scale of cognitive functioning in items of discriminative validity and internal consistency. However, known-groups comparison showed the expected clinical validity with PS for all the scales except for financial impact, and longitudinally clinical validity with KPS was shown in scales of cognitive functioning, fatigue, and nausea and vomiting. Multitrait scaling analysis showed that the predicted scales constituting quality of life (QOL) in the English-speaking culture were extracted from the Japanese QLQ-C30, and found to be valid in Japan, indicating its possible usefulness as an instrument that is universally applicable across cultures.     

Efficacy of ondansetron in radiation-induced nausea and vomiting: review of the literature

Radiotherapy-induced emesis depends on the site of irradiation, the field size and the dose per fraction and is generally less intense than chemotherapy-induced emesis. Established anti-emetic drugs offer only limited symptom control (50%). Ondansetron, a 5HT3 receptors antagonist, had proven a complete or a major control efficacy (0-2 emetic episodes) of 68 to 95% in three pilot studies (fractionated, single-dose and total body irradiations). In controlled studies, ondansetron efficacy was significantly higher than placebo, metoclopramide and prochlorperazine. The treatment was well tolerated in the different studies.     

Assessment of quality of life in a multicultural cancer patient population.

Quality of life (QOL) is increasingly assessed in cancer patients. In this article, the authors examined the psychometric performance of a commonly used QOL questionnaire, the Quality of Life Questionnaire--Cancer 30 (QLQ-C30; N. K. Aaronson et al., 1993), in multiethnic cancer patients. Content validation studies in patients and clinicians identified possible new items. Multiple-group confirmatory factor analysis supported equivalent structure across ethnic groups (Caucasians and Asian/Pacific Islanders [APIs]). A higher order QOL factor appeared to directly affect functioning scales and symptom count. Exploratory factor analysis examined effects of new items. Ten factors were extracted, 6 consistent with the original instrument and 4 reflecting potentially new aspects of QOL: Positive Social Support, Coping, Existential Well-Being, and Sexuality/Intimacy. The QLQ-C30 appears appropriate for use in API cancer patients. Further work needs to ensure that it includes all important domains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Review of the preclinical pharmacology and comparative efficacy of 5-hydroxytryptamine-3 receptor antagonists for chemotherapy-induced emesis

PURPOSE: This analysis was undertaken to review published reports of the comparative efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in the prophylaxis of acute chemotherapy-induced emesis. METHODS: Comparison data used are the preclinical pharmacology as well as the design and results of clinical trials. Seven comparative studies that used granisetron, ondansetron, or tropisetron in patients who received either moderately or highly emetogenic chemotherapy are reviewed. As the study designs, patient population, chemotherapy, antiemetic doses and schedule, and methods of assessment were slightly different, the results of each study are analyzed independently. Effectiveness is assessed by emetic episodes, nausea, and patient preference. RESULTS: The preclinical pharmacologic profile is different among the 5-HT3 antagonists in terms of potency, selectivity, dose response, and duration of action. The comparative clinical trials show that a single intravenous (i.v.) dose of granisetron 3 mg is as effective as multiple (8 mg x 3) or single (32 mg) i.v. doses of ondansetron for the prevention of acute nausea and emesis due to cisplatin. In the two moderately emetogenic clinical trials, granisetron 3 mg i.v. was at least as effective as ondansetron 8 mg i.v. +/- 24 mg orally and tropisetron 5 mg i.v. Patient preference was evaluated in three of the four crossover trials: granisetron was preferred in three of four, and no preference was reported in the fourth. The one trial to compare ondansetron 0.15 mg/kg x 3 versus granisetron 10 micrograms/kg x 1 or granisetron 40 micrograms/kg i.v. demonstrated equivalent control of nausea and vomiting in patients who received cisplatin-based chemotherapy. CONCLUSION: The 5-HT3 receptor antagonists compared are highly effective antiemetic agents that have now become the standard of care for preventing chemotherapy-induced emesis. Whether the described preclinical differences among these agents are also clinically significant remains to be seen. In the comparative trials analyzed, the 5-HT3 receptor antagonists demonstrated relatively equivalent clinical efficacy. Cost analysis may favor the use of one agent over another depending on the emetogenic challenge, dose of the 5-HT3 antagonists, and number of doses recommended. Patient preference may be an important factor to be considered in future antiemetic trials.     

In situ hybridization with riboprobes: an overview for veterinary pathologists

Although preliminary reports indicate that fatigue is a common symptom of human immunodeficiency virus (HIV) disease, little empirical research has focused on its prevalence or characteristics among patients with acquired immunodeficiency syndrome (AIDS). We assessed the frequency of fatigue and its medical and psychological correlates, in a cross-sectional survey of ambulatory AIDS patients. Ambulatory patients with AIDS who participated in a study of quality life (N = 427) were classified into fatigue/no fatigue groups based on their responses to fatigue items on the Memorial Symptom Assessment Scale (MSAS) and the AIDS physical symptom checklist. Self-report inventories were also administered to assess psychological distress, depressive symptoms, and overall quality of life. Medical information was elicited through clinical interview and review of medical chart. Fifty-four percent of the patients endorsed both of the fatigue items from the MSAS and the AIDS physical symptom checklists, and were classified as having fatigue. Women were significantly more likely to report fatigue than men (chi square = 5.28, df = 1, P < 0.03), and patients reporting homosexual contact as their transmission risk factor were significantly less likely to report fatigue than were patients reporting injection drug use or heterosexual contact (chi square = 5.13, df = 2, P < 0.03). The presence of fatigue was significantly associated with the number of current AIDS-related physical symptoms [t(425) = 8.00, P < 0.0001], current treatment for HIV-related medical disorders (chi square = 12.51, df = 1, P < 0.0001), anemia [t(174) = -2.35, P < 0.02], and pain (chi square = 36.36, df = 1 P < 0.0001). Patients with fatigue also had significantly poorer physical functioning ability [Karnofsky: t(422) = -6.27, P < 0.0001], as well as greater degree of overall psychological distress and lower quality of life [F(5,418) = 23.79, P < 0.0001], as measured by the Brief Symptom Inventory, Beck Depression Inventory, Beck Hopelessness Scale, Functional Living Inventory for Cancer (modified for AIDS), and the MSAS Psychological Distress Subscale. Fatigue is a common symptom in ambulatory AIDS patients and is associated with significant physical and psychological morbidity.     

Postoperative nausea and emesis: mechanisms and treatment

The incidence of postoperative emetic symptoms in patients varies between 3 and 91%. Nausea and emesis remain the most common as well as unpleasant side-effects experienced by patients following general anaesthesia, both in the ambulatory and non-ambulatory care setting. Furthermore, emesis carries the risk of severe postoperative complications and is associated with additional costs. Multiple factors are associated with an increased risk of developing postoperative nausea and emesis including age, gender, weight, preexisting disease, as well as anaesthetic and surgical procedures. Routine antiemetic prophylaxis is not currently advisable in patients with a low Emesis Risk, due to undesirable side-effects of antiemetics and additional costs. However, anti-emetic prophylaxis is recommended for patients with an increased risk. Besides administration of antiemetics, other factors that may provoke postoperative emesis need to be considered such as gastric distension, early mobilisation, insufficient analgesia, choice of anaesthetic drugs. High-risk patients may be anaesthetized with propofol, if possible. If symptoms do develop in the recovery room, tight fitting oxygen masks should be avoided and adequate hydration and analgesia ensured. To avoid side effects, antiemetics should be administered in minimally effective dosages. If emesis persists, combination of antiemetic drugs with different profiles of receptor action may be particularly useful.     

The EORTC core quality of life questionnaire (QLQ-C30): validity and reliability when analysed with patients treated with palliative radiotherapy

The EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) is designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items. 247 patients completed the EORTC QLQ-C30 before palliative radiotherapy and 181 after palliative radiotherapy. The questionnaire was well accepted with a high completion rate in the present patient population consisting of advanced cancer patients with short life expectancy. In addition, the questionnaire was found to be useful to detect the effect of palliative radiotherapy over time. The scale reliability was excellent for all scales except the role functioning scale. Excellent criterion validity was found for the emotional functioning scale where it was correlated with GHQ-20. Performance of the questionnaire was improved after the second evaluation as compared with the first. The present study shows that the EORTC QLQ-C30 is found to be practical and valid in measuring quality of life in patients with advanced disease.     

Quality of life assessment in patients receiving adjuvant therapy for breast cancer: the IBCSG approach. The International Breast Cancer Study Group

BACKGROUND AND PURPOSE: The International Breast Cancer Study Group (IBCSG) has developed and approach for assessing the impact of adjuvant therapy on quality of life (QL) within the framework of international, multilingual clinical trials. The major steps are summarized. Conceptual, methodological and practical issues are discussed with reference to results of two trials closed to accrual (IBCSG VI, VII) and one subsequent ongoing trial (IBCSG IX). PATIENTS AND METHODS: QL was assessed in pre- and post-menopausal patients with operable breast cancer. Various single-item linear analogue self-assessment (LASA) scales were used as indicators of components of QL, including global indicators of well-being, functioning and health perception, and specific indicators of symptoms of disease and treatment. In trials VI and VII, QL was assessed at baseline, during adjuvant treatment and follow-up, and at recurrence. Based on this experience, the QL form was revised for subsequent trials and further investigated in a subsample of patients randomized into trial IX. RESULTS: In trials VI and VII, the QL indicators were responsive to the impact of biomedical factors at baseline, various adjuvant treatments, changes over the first 18 months, and recurrence. In trial IX, the revised QL form was well accepted by patients and staff. Completing this form did not exceed five minutes. QL differences between on and off cytotoxic treatment strengthen the claim that these measures are responsive. Correlations and logistic regression analyses show the expected relationship among the various global and specific indicators. CONCLUSION: Results from two trials closed to accrual and an ongoing trial confirm the feasibility, validity and clinical relevance of the IBCSG approach for studying the impact of adjuvant breast cancer therapy on QL in international clinical trials.     

Suppression of crossing-over by DNA methylation in Ascobolus

Interpretation of health related quality of life (HRQOL) results in cancer patients is facilitated by knowledge of the levels of HRQOL in the general population. However, direct comparisons can be misleading unless age and gender are considered. We demonstrate the derivation of age- and gender-specific 'expected' values from population reference values by means of simple calculations. This survey included 3000 randomly selected Norwegians above 18 years of age who received the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30 (+3) by mail. 1965 responses from 2,892 eligible persons (68%) were received. The population was divided into six disease groups based on self-reported health problems. The observed mean scale scores of the different groups deviated greatly from those obtained in the general population. The score for physical function, for example, was 72 for cancer patients and ranged from 73.3 to 82.5 in other disease groups, as opposed to 89.9 in the general population and 98.9 in those with no health problems. The range for one of the quality of life (QOL) scales was 57.7 to 84.7 compared with 73.7 in the general population. Expected mean scores for the patient groups were computed from the reference values, based on the concept of equivalence of age and gender. The differences between the observed mean scores and the reference values were strongly mediated by this method. The expected scores for physical function then ranged from 83.3 to 93.1 and from 70.3 to 75 for the QOL scale. The impact of age and gender on the reference data from the EORTC QLQ-C30 (+3) obtained in a general population shows that these variables must be considered when interpreting data on HRQOL for cancer patients. The demonstration of how to generate mean values which are adjusted according to the age and gender distribution of a population should increase the usefulness of this questionnaire among clinicians.     

Radiographic mensuration characteristics of the sagittal lumbar spine from a normal population with a method to synthesize prior studies of lordosis

This multinational, multicentre, randomised, parallel-group study compared the safety, tolerability and efficacy of ondansetron 8 mg orally twice a day with ondansetron suppository 16 mg once daily in patients receiving cyclophosphamide-containing chemotherapy. A total of 406 patients were randomised to receive ondansetron 8 mg p.o. (198 patients) or ondansetron suppository (208 patients) medication in a double-blind, double-dummy trial. The primary efficacy analysis revealed that ondansetron provided good anti-emetic control with 81% of patients in the 8 mg p.o. b.d. group and 73% of patients in the 16 mg ondansetron suppository o.d. group experiencing complete or major control of emesis (< or = 2 emetic episodes) on the worst day of days 1-3. The 90% confidence interval for the difference between the two treatments for complete or major control (1.4, 15.0%) showed that the treatments could be regarded as equivalent. A difference in favour of oral ondansetron treatment was noted for the complete control (0 emetic episodes) rates over days 1-3, but no differences were found on day 1. There were no significant differences in the distribution of nausea grades between the treatment groups on the worst day of days 1-3 or on day 1. The incidence of adverse events was similar for the two treatment groups, the most frequently reported events were headache and constipation. There were no significant laboratory findings in either treatment group. In conclusion this study showed that the ondansetron treatments could be regarded as equivalent for the primary efficacy endpoint and that ondansetron suppository was well tolerated and effective in the prevention of cyclophosphamide-induced emesis.     

Gliomatosis cerebri: findings with computed tomography and magnetic resonance imaging

OBJECTIVES: In an effort to critically examine the antitumor activity of altretamine (hexamethylmelamine) as salvage therapy of platinum-refractory ovarian cancer, the Gynecologic Oncology Group initiated a Phase II trial of the agent administered in this clinical setting. METHODS: Altretamine was administered at a dose of 260 mg/m2 orally for 14 days in a 28-day course. Treatment was continued until disease progression or unacceptable side effects prevented further therapy. A total of 36 patients (median age: 56.5) were treated on this trial, of whom 33 were evaluable for toxicity and 30 for response. All patients had previously received either cisplatin or carboplatin and paclitaxel. RESULTS: The major side effect was emesis (grade 3-4, 7/33, 21%). The objective response rate was 10% (one complete response, two partial responses). CONCLUSION: We conclude that altretamine has limited activity in platinum-refractory ovarian cancer.     

Psychometric evaluation of the Multidimensional Assessment of Fatigue Scale for use with pregnant and postpartum women.

Although fatigue is a common experience for pregnant women and new mothers, few measures of fatigue have been validated for use with this population. To address this gap, the authors assessed psychometric properties of the Multidimensional Assessment of Fatigue (MAF) scale, which was used in 2 independent samples of pregnant women. Results indicated that the psychometric properties of the scale were very similar across samples and time points. The scale possesses a high level of internal consistency, has good convergent validity with measures of sleep quality and depression, and discriminates well from a measure of social support. Contrary to previous evaluations of the MAF, data strongly suggest that the scale represents a unidimensional construct best represented by a single factor. Results indicate that the MAF is a useful measure of fatigue among pregnant and postpartum women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of oral and intravenous ondansetron in patients treated with cisplatin

Ondansetron, a selective 5-HT3 antagonist, has been shown to be effective in preventing chemotherapy-induced nausea and vomiting. From July and August 1991, 25 patients were accrued in a phase II study to assess the efficacy of ondansetron in patients receiving cisplatin-containing chemotherapy. Patients received intravenous cisplatin 100 mg/m2, given either as a 24-hour infusion on day 1 or in divided doses as eight-hour infusions daily on days 1 to 3. Each patient received 24 mg of ondansetron per day for six days. Intravenous dexamethasone 24 mg was given daily on the days of cisplatin infusion. The emetic episodes and degree of nausea were evaluated daily. "Good" control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) ranged from 64-100% and 88-100% respectively. Failure in emesis control occurred most frequently on days 3 and 4. Ondansetron was generally well tolerated with only minimal side-effects. One patient developed unexplained encephalopathy which resolved completely. Our results suggest that ondansetron is an effective anti-emetic agent with minimal toxicities. Randomised studies comparing ondansetron against "standard" anti-emetics should be conducted.     

The development and psychometric validation of a brain cancer quality-of-life questionnaire for use in combination with general cancer-specific questionnaires

A self-report questionnaire module consisting of 24 items, comprising 5 scales and 7 single items, has been developed for measuring health-related quality of life in patients with brain cancer. Module development proceeded through several stages, including a listing of patient, family and health care professional concerns, the writing of items, field testing in 105 patients with brain cancer and subsequent item reduction and scale construction after multitrait scaling analysis and assessment of internal consistency (Cronbach's coefficient alpha). The final version of the module exhibits reasonable test-retest stability over a period of one week. Differences in the responses between patients with recently-diagnosed and recurrent cancer and between patients with a Karnofsky Performance Score (KPS) of 50-70 and 80-100 were in the expected direction, indicating that the module of questions is responsive to differing conditions. Patients with either mental confusion, motor deficit or dysphasia indicated problems in several domains and single items as compared to patients without these neurological deficits. Thus, differences in the responses to the items in the brain cancer module appear to reflect differences in neurological status. In addition, deteriorating neurological status was accompanied by a marked increase in emotional distress, future uncertainty and motor dysfunction. A comparison of the responses in the module with the KPS and with a modified Barthel Activities of Daily Living Index (BADLI) shows moderate correlations, primarily with scales and items that pertain to motor dysfunction, while other scales (such as emotional distress, visual disorder and communication deficit) and most single items are not associated with the KPS or BADLI. Since the emotional distress scale of the module was found to be highly correlated with the emotional function scale of the EORTC QLQ-C30, it could be omitted when the module is used in combination with the QLQ-C30. This would reduce the module to a total of 20 items with four scales and seven single items. The intention is to combine this module of questions with other core or general quality-of-life questionnaires when studying patients with brain cancer in clinical trials.     

In utero transplantation of human fetal haemopoietic cells in NOD/SCID mice

BACKGROUND: Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease. METHODS: The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (> 70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days. RESULTS: All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days. CONCLUSIONS: After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.     

What is core? Guidelines for the core curriculum in paediatrics

This multicentre, randomised, double-blind, double-dummy, parallel group study was investigated in order to compare on 3 days the efficacy and the safety of the 16 mg once a day (od) ondansetron suppository (suppository group) with the recommended ondansetron treatment, i.e. 8 mg intravenous (i.v.) ondansetron on day 1 followed by 8 mg tablet (p.o.) twice daily (i.v. + p.o. group) on days 2 and 3 in patients receiving cisplatin (> or = 50 mg/m2) containing chemotherapy. In the 420 patients included in the intent-to-treat population, 209 received the 16 mg suppository and 211 the i.v. + p.o. treatment. The number of emetic episodes and the nausea score were recorded each day. Concerning the primary criterion, both treatments provided good anti-emetic control with 87% of all patients having a complete or major response (0-2 emetic episodes) on day 1 in the suppository group and 92% in the i.v. + p.o. group (P = 0.058). The 90% confidence interval for the difference between the two treatments for complete or major control was included in the interval (-15%, 15%) and showed that the treatment groups could be regarded as equivalent. Small differences in favour of the i.v. + p.o. group were observed concerning the secondary parameters. Both treatments were well tolerated. The results of this study show that both treatments are equivalent in the prevention of cisplatin-containing chemotherapy induced emesis for the primary efficacy criteria and that the ondansetron suppository is efficient and well tolerated and is a suitable alternative to the anti-emetic treatment combining the intravenous and oral routes.     

The treatment of inclusion body myositis: a retrospective review and a randomized, prospective trial of immunosuppressive therapy

We have sought to examine the response to immunosuppressive therapeutic intervention in inclusion body myositis (IBM) in a retrospective review of prior responses to therapy and in an open, randomized crossover trial. We collected information on the response to prior therapy on 25 patients, and for prospective therapy on 11 of these patients. All met criteria for a definite idiopathic inflammatory myopathy and had biopsy-proven IBM. Clinical and laboratory results were assessed by interviews of patients and by chart review in the retrospective trial. Manual muscle strength was assessed by a single trained observer; the patients' activities of daily living were assessed by questionnaire; and serum tests of muscle-associated enzymes were measured in the prospective trial. In the retrospective review, prednisone appeared to have been of some, albeit modest, clinical benefit in 10 of 25 (40%) patients. Other therapies, primarily azathioprine and methotrexate, also appeared to have halted the progression of weakness in 8 of 35 trials (23%). In the prospective study, combination therapy of oral azathioprine and methotrexate and a biweekly infusion of high-dose intravenous methotrexate with leucovorin rescue were given for 3 to 6 months in an open, crossover design. Both the oral and the intravenous regimens were clinically effective in some patients. There was clinical improvement in 3 trials, stabilization in 11 trials, and worsening in 5 trials, out of a total of 19 completed (22 intended) trials. The presence of active inflammation at entry into the prospective therapeutic protocol, either directly observed on muscle biopsy or indirectly indicated by serum creatine kinase level, may have been associated with clinical improvement. A complete laboratory response with normalization of creatine kinase and other muscle-associated enzymes did not, however, significantly predict clinical responsiveness in the prospective trial. In this first report, to our knowledge, of a prospective trial of immunosuppressive therapy for this disease, stabilization and even slight improvement of strength and functional abilities appeared to be achieved in some patients. We believe that prednisone and other immunosuppressive therapies were of modest benefit in about half of patients with inclusion body myositis, especially those with some evidence of active inflammation. Stabilization of an otherwise inexorably deteriorating course appears, therefore, to be an attainable goal in some patients with IBM.