Wait times for diagnosis and treatment of lung cancer: a single-centre experience.

BACKGROUND: Multiple clinical practice guidelines recommend rapid evaluation of patients with suspected lung cancer. It is uncertain whether delays in diagnosis and management have a negative effect on outcomes. METHODS: This retrospective study included 551 patients diagnosed with lung cancer through the diagnostic assessment program at the Institut universitaire de cardiologie et de pneumologie de Québec between September 2013 and March 2015. Median wait times between initial referral, diagnosis, and first treatment were calculated and compared with recommended targets. Analyses were performed to evaluate for specific factors associated with longer wait times and for the effect of delays on the outcomes of progression-free survival (pfs), relapse-free survival (rfs) after primary surgical resection, and overall survival (os). RESULTS: Most patients were investigated and treated within recommended targets. Of the entire cohort, 379 patients were treated at our institution. Of those 379 patients, 311 (82%) were treated within recommended targets. In comparing patients within and outside target times, the only statistically significant difference was found in the distribution of treatment modalities: patients meeting targets were more likely to be treated with surgery or chemotherapy rather than with radiation. The pfs on first treatment modality was influenced by clinical stage, but not by time to therapy [hazard ratio (hr): 1.10; p = 0.65]. The os for the entire cohort was also influenced by stage, but not by delays (hr: 1.04; p = 0.87). For the 209 patients treated by surgery with curative intent, a significant reduction in rfs was associated with male sex and TNM stage, but not with delays (hr: 1.11; p = 0.83). The os after primary surgical resection was also associated with TNM stage, but not with delays (hr: 1.82; p = 0.43). CONCLUSIONS: Recommended targets for wait times in the investigation and treatment of lung cancer can be achieved within a diagnostic assessment program. Compared with radiation treatment, treatment with surgery or chemotherapy is more likely to be completed within targets. Delays in investigation and treatment do not appear to negatively affect the clinical outcomes of os, rfs, and pfs. Prospective studies are needed to evaluate whether efficient work-up and treatment influence other important variables, such as quality of life, cost of care, and access to therapies while performance status is adequate.

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29.

INTRODUCTION: This randomised double-blind placebo-controlled study evaluated the addition of cediranib, an inhibitor of vascular endothelial growth factor receptors 1-3, to standard carboplatin/paclitaxel chemotherapy in advanced non-small cell lung cancer. METHODS: Eligible patients received paclitaxel (200mg/m(2)) and carboplatin (area under the concentration time curve 6) intravenously every 3 weeks. Daily oral cediranib/placebo 20mg was commenced day 1 of cycle 1 and continued as monotherapy after completion of 4-6 cycles of chemotherapy. The primary end-point of the study was overall survival (OS). The trial would continue to full accrual if an interim analysis (IA) for progression-free survival (PFS), performed after 170 events of progression or death in the first 260 randomised patients, revealed a hazard ratio (HR) for PFS of ⩽ 0.70. RESULTS: The trial was halted for futility at the IA (HR for PFS 0.89, 95% confidence interval [CI] 0.66-1.20, p = 0.45). A final analysis was performed on all 306 enrolled patients. The addition of cediranib increased response rate ([RR] 52% versus 34%, p = 0.001) but did not significantly improve PFS (HR 0.91, 95% CI 0.71-1.18, p = 0.49) or OS (HR 0.94, 95% CI 0.69-1.30, p=0.72). Cediranib patients had more grade 3 hypertension, diarrhoea and anorexia. CONCLUSIONS: The addition of cediranib 20mg daily to carboplatin/paclitaxel chemotherapy increased RR and toxicity, but not survival.

Responses of Eastern red-backed salamanders (Plethodon cinereus) to chemical cues of prey presented in soluble and volatile forms.

Terrestrial salamanders are able to detect prey items using chemical cues, but the nature of the cues involved is uncertain. This study aimed to tease apart the roles of the soluble and volatile components of prey cues detected by Eastern red-backed salamanders (Plethodon cinereus), assuming the likelihood that these different components are respectively detected by the vomeronasal (accessory) and main olfactory organs. Wild-caught salamanders were exposed to control or soluble and volatile cricket cues in two different behavioural assays conducted in the laboratory. The first series of assays focused on localized presentation of soluble cues on the substrate, and the second on point sources of volatile cues delivered through plastic tubes. Room temperature was varied across experiments. Salamanders increased chemoinvestigation of the substrate via nosetapping when soluble prey cues were distributed non-uniformly on the substrate. In the warmer of two temperatures tested, salamanders additionally showed a spatial preference for location of soluble cue deposition. Attraction to a point source of volatile cues was not evident when examining the responses of salamanders grouped together; however, investigation of the volatile point source was significantly correlated with side preference only when both soluble cues and a volatile point source were present. The latter suggests that a subset of salamanders were attracted to the point source of volatile cues in the presence of soluble cues on the substrate. This study indicates that soluble prey cues alone are sufficient to trigger salamander foraging behaviour, and that temperature influences this foraging response. It supports the notion that the vomeronasal system plays an important role in prey detection, but suggests that volatile cues are also investigated by some salamanders when soluble prey cues have been detected.

High convergence of olfactory and vomeronasal influence in the telencephalon of the terrestrial salamander Plethodon shermani.

Previous work suggested that the telencephalic pathways of the main olfactory and vomeronasal systems of vertebrates are mostly isolated from each other, with the possible exception of convergence of the two systems into a small part of the olfactory amygdala. We tested the hypothesis of convergence between the main olfactory and vomeronasal systems by investigating the physiology of telencephalic olfactory responses in an in vitro brain preparation of the salamander Plethodon shermani. This animal was chosen because its olfactory and vomeronasal nerves can be separated and stimulated independently. The nerves were stimulated by short current pulses delivered through suction electrodes. Evoked field potentials and intracellular responses were systematically recorded in the telencephalon. The results showed an abundant overlap of olfactory and vomeronasal nerve-evoked field potentials in the ipsilateral lateral telencephalon and the amygdala. Single neurons receiving bimodal main olfactory and vomeronasal input were found in the dorsolateral telencephalon and amygdala. A classification of response latencies suggested that a subset of these neurons received direct input from both the main and accessory olfactory bulbs. Unimodal excitatory main olfactory responses were mostly found in neurons of the caudal telencephalic pole, but were also present in the striato-pallial transition area/lateral pallium region and striatum. Unimodal excitatory vomeronasal responses were found in neurons of the striato-pallial transition area, vomeronasal amygdala, and caudal amygdala. We conclude that the main olfactory and vomeronasal systems are extensively integrated within the salamander telencephalon and probably act in concert to modulate behavior.

Treatment-emergent hypertension and outcomes in patients with advanced non-small-cell lung cancer receiving chemotherapy with or without the vascular endothelial growth factor receptor inhibitor cediranib: NCIC Clinical Trials Group Study BR24.

BACKGROUND: Hypertension (HTN), a recognized adverse effect of angiogenesis inhibitors, may be a potential biomarker of activity of these agents. We conducted a retrospective analysis to examine the incidence and predictors of the development of on-treatment HTN with the vascular endothelial growth factor receptor tyrosine kinase inhibitor cediranib, and the relationship of this adverse event with treatment outcomes. PATIENTS AND METHODS: BR24 was a double-blind placebo-controlled phase II trial of carboplatin/paclitaxel chemotherapy with either daily oral cediranib or placebo in patients (n = 296) with advanced non-small-cell lung cancer (NSCLC). Exploratory analyses characterized relationships between HTN, baseline variables, and efficacy outcomes. RESULTS: New onset or worsening of preexisting HTN (treatment-emergent HTN) was more frequent in patients receiving cediranib (68 versus 45%, P < 0.0001). Factors associated with HTN in all randomized patients were good performance status and treatment with cediranib. In both arms, treatment-emergent HTN was associated with improved efficacy outcomes, but there was no evidence of a differential treatment effect, with nonsignificant interaction P values. CONCLUSIONS: In advanced NSCLC, HTN is frequent in patients receiving chemotherapy, with or without cediranib. The development of HTN was favorably prognostic in these patients, but not predictive of a differential outcome with cediranib.

Courtship pheromone-induced c-Fos-like immunolabeling in the female salamander brain.

Plethodontid salamanders display intricate courtship behaviors. Proteinaceous courtship pheromones were recently discovered in the submandibular (mental) gland of the male Plethodon shermani, the red-legged salamander. Behavioral studies showed that these male pheromones are delivered by direct contact to the female snout and modulate her receptivity during courtship. Previous reports demonstrated that experimental application of courtship pheromones activates vomeronasal sensory neurons in P. shermani. The present study investigated the CNS response to courtship pheromones in that species using immunocytochemical detection of the immediate-early gene product c-Fos. The results show that application of a male gland extract to females activated Fos-like immunolabeling in the extended vomeronasal amygdala of the accessory olfactory system, as well as in the preoptic area and ventromedial hypothalamus; regions of the brain known to mediate reproductive responses in vertebrates. The gland extract additionally activated Fos-like labeling in the raphe median, possibly indicating a serotonergic activation. Application of individual purified courtship pheromone proteins resulted in increases in Fos-like labeling in some of the regions activated by the complete submandibular gland extract, but the pattern of labeling was not as clear as that of the complete extract. Unlike other known vertebrate reproductive pheromones, courtship pheromones in P. shermani were effective only at a high concentration. This could result from the particular mode of pheromone transfer in that species, which involves sustained direct contact between male and female. It is concluded that salamander courtship pheromones exert their influence on behavior through the vomeronasal pathway and its direct projections to the preoptic and hypothalamic regions.

Docetaxel and Gemcitabine administered on days 1 and 8 for metastatic non-small cell lung carcinoma (NSCLC): a phase II multicenter trial.

Docetaxel and Gemcitabine are active agents in non-small cell lung carcinoma (NSCLC). They have different mechanism of action, minimal overlapping toxicity, and are easily administered on an outpatient basis. This phase II study evaluated Docetaxel administered with Gemcitabine on days 1 and 8 in a 3-week cycle, to determine its efficacy, while attempting to lower the regimen's toxicity, especially myelosuppression which can occur when Docetaxel is administered at full dose on day 1 only. Forty-three chemonaive patients, 40 evaluable, were entered in this trial between May 2001 and March 2002. Thirty-seven patients had stage IV and three patients had stage III B NSCLC, median age 58 (ages 32-78), median performance status (PS) 1 (range 0-2). They were treated with Docetaxel 36mg/m(2) and Gemcitabine 1000mg/m(2) intravenously on days 1 and 8 in a 3-week cycle. No growth factors were administered. Of 40 evaluable patients, 4 achieved partial response (10%), 25 stable disease (62.5%) and 11 progressive disease (27.5%). Median time-to-disease progression was 15 weeks. Median survival was 7.75 months. One year survival was 32.5% (13 patients). Hematologic toxicity was minimal, non-hematologic toxicity was easily treatable. Docetaxel, when given with Gemcitabine on days 1 and 8 every 3 weeks, is less myelotoxic, yet still an effective treatment for metastatic NSCLC.

Non-oscillatory discharges of an F-prostaglandin responsive neuron population in the olfactory bulb-telencephalon transition area in lake whitefish.

Our previous studies on olfactory bulbar responses in salmonid fishes suggest that pheromone signals might be processed by a mechanism distinct from that of other odorants. Using in vivo single-unit and electroencephalographic recordings, we investigated response characteristics of olfactory neurons in lake whitefish, Coregonus clupeaformis, a species characterized by high electrophysiological and behavioral sensitivities to the reproductive pheromone candidates F-prostaglandins. We found a neuron population responsive to F-prostaglandins in the ventromedial brain tissue strip connecting the olfactory bulb to the telencephalon. Of the 64 neurons examined in this area, 33% showed excitatory and 11% inhibitory responses to F-prostaglandins, while 52% were non-responsive to all the stimuli tested. Both phasic and tonic F-prostaglandin neuron response patterns were observed during the 10-s stimulus period; some responses were delayed from the onset of stimulation, and some persisted for a long time following stimulus cessation. This neuron population did not induce synchronized oscillatory waves upon stimulation with F-prostaglandins, despite massive discharges. We demonstrate for the first time that the olfactory bulb-telencephalon area of the brain is a distinct neural structure through which putative reproductive pheromone signals are integrated. Amino acid and F-prostaglandin neuron population discharges have different temporal characteristics, suggesting different processing mechanisms exist for odorant and pheromone signals. The observed sustained neuron discharges may play a role in amplifying pheromone signals required for triggering stereotyped neuroendocrine and/or behavior changes.

Neurobiology of fish olfaction: a review.

The last decade saw important advances in our understanding of the olfactory system function. In some animals, we now have the basic knowledge necessary to investigate coding mechanisms employed in olfaction. So far, studies of the fish olfactory system have focused on odor detection and the early processing of olfactory information in the olfactory bulb. How this information is integrated in the forebrain is unknown. Here, we first describe the anatomy of the fish olfactory system. The problems faced when describing the anatomy of the terminal nerve complex and nucleus olfactoretinalis are highlighted. Olfactory sensory neurons are randomly distributed over the entire olfactory epithelium, a unique feature of the olfactory sense. These primary olfactory neurons converge upon their second-order targets in segregated areas of the olfactory bulb. Exchange of information occurs in the glomeruli and glomerular plexus, where primary neurons synapse on mitral cell dendrites. The spatial distribution of glomerular activity induced by odorants of different classes shows that distinct neuron populations of the olfactory bulb encode information related to different odorant groups. In most cases, these neuron populations synchronize their alternating sequences of firing and silence when stimulated by primary input. Synchronized oscillations of these second-order neurons could contain important coding information, or represent a mechanism by which learning is facilitated. Alternatively, oscillations could be solely used to shape the olfactory bulb response. The nature of the olfactory information that reaches the forebrain and decoding of this information by the central nervous system are discussed.

Comparative efficacy and safety of controlled-release morphine suppositories and tablets in cancer pain.

Although the oral route is the preferred method of opioid therapy in patients with cancer pain, many patients will require an alternate route of analgesic administration at some point during the trajectory of their illness. This study compared the efficacy and safety of a novel, controlled-release suppository of morphine (MSC-R) and controlled-release morphine tablets (MSC-T) in patients with cancer pain. In a double-blind crossover study, 27 patients with cancer pain were randomized to receive MSC-R or MSC-T every 12 hours for 7 days each, using a 1:1 analgesic equivalence ratio. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed with a VAS. Pharmacodynamic assessments were made by the patient at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM and rescue morphine use recorded in a daily diary. There were no significant differences between MSC-R and MSC-T in overall scores for pain intensity VAS, ordinal pain intensity, and sedation. There was a small but significant difference in overall nausea VAS score in favor of MSC-R. Mean daily rescue analgesic use did not differ significantly during between treatment with MSC-R and MSC-T. MSC-R provides pain control comparable to that provided by MSC-T when given every 12 hours at a 1:1 dose ratio, and represents a reliable alternative method of pain control for patients unable to take oral opioid agents.

Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.

Fever in goldfish is induced by pyrogens but not by handling.

Six goldfish, Carassius auratus, weighing 2.5 to 4 g were placed individually in an aquarium with two communicating chambers. One chamber was thermostatted at 34 degrees C, the other at 37 degrees C. In control Session a, without external intervention, fish selected the cooler chamber most of the time and stayed only 4.8 +/- 1.1 min/2 h at 37 degrees C. In Session b, infectious fever was assayed: pyrogen (Salmonella typhosa LPS, or human interleukin-2) was injected intracranially and fish stayed 44.7 +/- 15.3 min/2 h at 37 degrees C. In Session c, behavioral stress was achieved by chasing the fish with a net, catching it, handling it out of water, and injecting 10 microL of saline intracranially. Fish stayed 2.7 +/- 1.0 min/2 h at 37 degrees C. Analysis of variance showed that stay at 37 degrees C was significantly longer in Session b than a and c, and that Sessions a and c were not significantly different from one another. This result confirms the existence of behavioral fever, but does not support the hypothesis of fever in fish after handling.

Phase II trial of docetaxel with dexamethasone premedication in patients with advanced non-small cell lung cancer: the Canadian experience.

We performed a Phase II trial to evaluate the activity and tolerability of docetaxel as a single agent in the treatment of advanced non-small cell lung cancer (NSCLC). Forty-four patients with metastatic and/or locally advanced NSCLC received i.v. docetaxel 100 mg/m2 every 3 weeks for a median of 4 (range 1-11) cycles. All patients received premedication with oral dexamethasone 8 mg twice daily for 5 days starting the day before chemotherapy. Seven partial responses were observed among 35 evaluable patients, and the overall response rate was 20% (95% CI 8-37). The median response duration was 5 months, median survival time was 10 months and the estimated 1-year survival rate was 42%. Treatment was generally well tolerated. Febrile neutropenia occurred in 10 patients (23%); neutropenic infection occurred in 4 patients, and led to 2 toxic deaths (both patients had borderline exclusion criteria). The corticosteroid premedication effectively reduced the overall incidence (34%) and severity (4% severe) of fluid retention, and delayed the median time to onset from cycle 4 to cycle 7. This study shows the promising efficacy of docetaxel as monotherapy in advanced NSCLC, and combination chemotherapy regimens incorporating docetaxel are now being evaluated in this clinical setting.

A randomized, double-blind, placebo-controlled study of lorazepam as premedication for bronchoscopy.

To our knowledge, no study has clearly demonstrated the advantage of sedative premedication for bronchoscopy. In a double-blind study, we evaluated the efficacy of oral lorazepam as premedication for bronchoscopy. One hundred patients were randomly assigned to receive placebo (group A) or lorazepam (2 mg) (group B) approximately 1.5 h before bronchoscopy. Immediately after the procedure and the following day, a questionnaire addressing the patient's perception of the procedure was administered. Specifically, subjects were asked to grade the bronchoscopy as very easy, easy, difficult, or very difficult to tolerate and if they would agree to a second bronchoscopy if believed necessary. In addition, their recollection of the procedure was graded as clear, indistinct, or not at all. No difference was found between the two groups for age, duration of the bronchoscopy, and the answers to the questionnaire administered immediately after the procedure. Most patients from both groups found their level of sedation adequate. On the following day, however, group B reported with lower frequency that the technique was difficult or very difficult (38.0% vs 65.3% for group A; p < 0.005) and that they would be less reluctant to a repeated bronchoscopy (30.0% vs 57.1% for group A; p < 0.015). Moreover, their recollection of the procedure was now less precise than for those who had received the placebo (p < 0.005). This suggests that the difference observed between the two groups at 24 h was related to the amnesic effect of lorazepam. We conclude that lorazepam, by improving patient's perception of the bronchoscopy, is a useful premedication and may facilitate patient's investigation when a second bronchoscopy becomes necessary.

Dexamethasone improves the efficacy of granisetron in the first 24 h following high-dose cisplatin chemotherapy.

The object of the study was to determine whether dexamethasone improved the efficacy of the serotonin receptor (5-HT3) antagonist granisetron in controlling acute (within 24 h) emesis in cancer patients receiving high-dose cisplatin chemotherapy and to ascertain whether continuation of granisetron after 24 h reduces the occurrence of delayed emesis. This randomised, double-blind, multicentre, three-arm study was conducted at 21 medical centres. A group of 292 nausea- and emesis-free patients with cancer, who had never had chemotherapy and were scheduled to receive at least 50 mg/m2 cisplatin, were given 3 mg granisetron i.v. in a 15-min infusion with or without 10 mg dexamethasone i.v. completed 5 min prior to high-dose cisplatin and 1 mg granisetron p.o. at +6 h and +12 h. Primary study end-points were control of emesis and nausea. Patients completed a self-report diary every 6 h for the first 24 h. At the end of the 24-h period, the patients who received dexamethasone had a significantly higher complete protection rate from emesis (64% compared to 39%) than those who received no steroid. Similarly, the dexamethasone-treated group had a significantly higher complete plus partial (0-2 emetic episodes) protection rate (84% compared to 64%). This study shows that dexamethasone markedly enhances the antiemetic efficacy of granisetron for acute-onset emesis in high-dose cisplatin chemotherapy.

Influence of lung volume on collateral resistance during methacholine-induced bronchospasm.

We tested the hypothesis that lung inflation in response to a bronchospasm could be beneficial by maintaining the lung collateral channels open. Six mild asthmatics were studied on 2 separate days. The first day we determined the methacholine dose response and measured collateral resistance (Rcoll) before and during the metacholine-induced bronchospasm and the effects of decreasing lung volumes on Rcoll. The lung volume changes were induced by applying progressively increasing positive extrathoracic pressures (PEP). The second day we measured the changes in end-expiratory lung volume (EELV) resulting from the inhaled methacholine and from the applied positive extrathoracic pressure. With the inhalation of methacholine, the FEV1 decrease ranged from 26-43% of the baseline values while Rcoll increased significantly in only three of the six subjects. EELV remained unchanged in one subject and increased by 1408, 990, 260, and 44 ml in four others. It was not measured in one subject. Decreasing EELV by PEP increased Rcoll in all subjects. By extrapolation of the lung volume-Rcoll relationship, we calculated that Rcoll would have increased by 18,227%, 6843%, 994%, 140%, and 128% if EELV had not increased in the five subjects in whom delta EELV was measured. We conclude that an increase in EELV in response to an induced bronchospasm helps maintain open and functional collateral pathways despite the bronchoconstriction.

Impact of chemotherapy-associated nausea and vomiting on patients' functional status and on costs: survey of five Canadian centres.

OBJECTIVE: To estimate the effect of chemotherapy-associated nausea and emesis on patients' functional status and on costs to the health care system, the patients and society before antagonists to the serotonin (5-hydroxytryptamine) receptor subtype 5-HT3 became available. DESIGN: A 5-day prospective survey between February and May 1991 of patients receiving chemotherapy for cancer. Data were obtained from questionnaires completed by nurses and patients. SETTING: Five Canadian cancer treatment centres in Ontario (three) and Quebec (two). PATIENTS: Outpatients and inpatients 18 years of age and older who were scheduled to receive chemotherapy with a moderate to high potential for emesis as defined by standardized criteria. Patients were excluded if they were scheduled to receive an investigational antiemetic or had received chemotherapy within the previous 7 days. Of the 128 who were eligible, 112 agreed to participate; 107 returned the completed questionnaire, but the data for 15 were excluded because the patients received multiple-day chemotherapy. MAIN OUTCOME MEASURES: The degree of nausea (on a seven-point scale) and the frequency of emesis (vomiting or retching) were recorded for each day of the survey. Functional status was assessed before and after chemotherapy by means of the Functional Living Index-Emesis (FLIE). The direct health care costs and the indirect costs (e.g., of time off work) associated with nausea and emesis were estimated from the survey responses and secondary data sources. RESULTS: On the day of chemotherapy 38 of the 92 patients (41%) experienced emesis with or without nausea, and over the 5 days of the survey 72 patients (78%) reported at least one episode of nausea or emesis. The absolute risk of either problem decreased over time, but the risk of nausea relative to emesis increased over time. The FLIE scores indicated significant worsening of functional status after chemotherapy. On the day after treatment the main impact was from emesis, particularly with regard to leisure activities, household tasks and hardship to the family. Nausea had a significantly greater impact than emesis on overall functioning. The additional direct health care cost for managing emesis was estimated to be $63 and the indirect cost $121. CONCLUSIONS: Despite prophylaxis with antiemetic drugs, nausea and emesis were significant problems in this population receiving chemotherapy. The management of emesis consumed relatively small amounts of health care resources, but there were costs outside the hospital for patients and others.

A randomised, double-blind comparison of granisetron with high-dose metoclopramide, dexamethasone and diphenhydramine for cisplatin-induced emesis. An NCI Canada Clinical Trials Group Phase III Trial.

151 patients (149 evaluable) receiving their first course of chemotherapy containing cisplatin in a dose of at least 50 mg/m2 were randomised to receive either a single dose of intravenous granisetron 80 micrograms/kg or intravenous metoclopramide 2 mg/kg every 2 h for five doses plus a single dose of dexamethasone 10 mg and diphenhydramine. After 24 h, there was no significant difference between groups with respect to nausea or vomiting: in the granisetron group 46% of patients had no emesis, versus 44% of the standard group. Granisetron is an antiemetic agent with efficacy similar to that of high-dose metoclopramide plus dexamethasone.

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-naïve 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)

Superiority of granisetron to dexamethasone plus prochlorperazine in the prevention of chemotherapy-induced emesis.

Trials of selective 5-hydroxytryptamine3 receptor antagonists have shown excellent antiemetic activity for chemotherapy containing cisplatin when compared with high-dose metoclopramide. There is little information about the efficacy of these new agents for chemotherapy other than for high-dose cisplatin. We performed a double-blind, randomized trial comparing a single dose of the 5-hydroxytryptamine3 receptor antagonist granisetron (BRL 43694A) as a single intravenous dose with dexamethasone plus prochlorperazine in 152 patients receiving their first course of moderately emetogenic chemotherapy (mainly doxorubicin- and cyclophosphamide-containing combinations). During the first 24 hours, there was a statistically significant advantage for the granisetron group in terms of the prevention of both nausea and emesis. There was no difference in the frequency of reported adverse events. We conclude that granisetron is more effective than dexamethasone plus prochlorperazine in patients who are receiving moderately emetogenic cytotoxic agents.