Options in the treatment of chemotherapy-induced emesis

PURPOSE: The incidence and duration of chemotherapy-induced emesis, pathophysiology of the emetic response, and antiemetic treatment of options are reviewed. OVERVIEW: Nausea and vomiting are among the most common and debilitating side effects of cancer chemotherapy. If not controlled, these side effects may interfere with the delivery of potentially life-saving treatment. Acute, delayed, and anticipatory nausea and vomiting may be prevented by appropriate antiemetic therapy. Drug selection is based on the emetogenicity of the patient's cancer treatment and potency of the antiemetic agent. Efficacy and safety of the antiemetic regimen are often improved by combining agents with different mechanisms of action. CLINICAL IMPLICATIONS: By preventing and controlling chemotherapy-induced emesis, clinicians may improve cancer patients' functional status and quality of life significantly. Improved tolerability may lead to greater patient acceptance of chemotherapy and prevent premature withdrawal from or cessation of treatment. Controlling chemotherapy-induced emesis also helps to decrease the direct and indirect costs of managing cancer.     

Clinical studies of oral antiemetic drugs on delayed emesis induced by cancer chemotherapy]

BACKGROUND AND PURPOSE: Our purpose was to develop a classification scheme and method of presentation of in vivo single-voxel proton spectroscopic data from astrocytomas that most closely match the classification scheme determined from biopsy specimens. Since in vivo proton spectroscopy is noninvasive, it may be an attractive alternative to intracranial biopsy. METHODS: Single-voxel spectra were acquired using the point-resolved spectroscopic pulse sequence as part of the Probe spectroscopy package on a G.E. 1.5-T Signa scanner. Subjects consisted of 27 patients with biopsy-confirmed brain tumors (13 with glioblastoma multiforme, six with anaplastic astrocytoma, and eight with low-grade astrocytoma). The patients were divided into groups based on the histologic subtype of their tumor for different treatment protocols. RESULTS: Metabolic peak areas were normalized for each metabolite (choline, creatine, N-acetylaspartate, lactate) to the area of the unsuppressed water peak and to the area of the creatine peak. Kruskal-Wallis nonparametric analysis of variance (ANOVA) tests showed statistically significant differences among the tumor groups for all the area ratios. The lactate/water ratio could be used to distinguished all three tumor groups, whereas the choline/water ratio distinguished low-grade astrocytomas from the two high-grade groups. Both the choline and lactate ratios could be used to separate the high-grade from the low-grade tumors. CONCLUSION: Specific relative metabolic peak area ratios acquired from regions of contrast-enhancing brain tumor can be used to classify astrocytomas as to histopathologic grade.     

Behavioral treatment of chemotherapy-induced nausea and vomiting

Nausea and vomiting associated with chemotherapy most commonly occur after administration of the drug regimen, but a substantial proportion of patients also develop these symptoms in anticipation of treatment, after one or more courses of chemotherapy have been given. Currently available pharmacologic agents are unable to provide complete protection from either anticipatory or post-treatment nausea and emesis associated with cancer chemotherapy. Since anticipatory nausea and vomiting are believed to become conditioned responses through the learning process of classical conditioning, behavioral treatments may be particularly appropriate. Progressive muscle relaxation training is effective in preventing as well as decreasing the frequency of postchemotherapy nausea and vomiting, whereas systematic desensitization has been found to be more effective against anticipatory nausea and emesis. Hypnosis and cognitive distraction have been used mainly in children and adolescents.     

Tropisetron in the prevention of acute and delayed nausea and vomiting over six courses of emetogenic chemotherapy

Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).     

Randomised double-blind study comparing tropisetron alone and in combination with dexamethasone in the prevention of acute and delayed cisplatin-induced emesis

In order to determine whether infection with Schistosoma japonicum is related to a higher rate of infection with hepatitis B virus and/or to a higher probability of HBsAg chronic carriage, a population based survey was carried out in China in which HBV markers were studied in 112 subjects with long-lasting S. japonicum infection, and 93 subjects with no S. japonicum infection 37.5% of the cases and 40.9% of controls showed no markers of HBV infection. The prevalence rate of HBsAg was 12.5% in the cases and 12.9% in the controls. For anti-HBc and anti-HBs the figures were 59.8% and 59.8%, and 27.9% and 35.0%, respectively. These data do not support the hypothesis of an interaction between infection with hepatitis B virus and S. japonicum.     

Antiemetic efficacy of granisetron in pediatric cancer treatment--(2). Comparison of granisetron and granisetron plus methylprednisolone as antiemetic prophylaxis

A crossover clinical trial was carried out to compare the effectiveness and safety of granisetron alone (40 micrograms/kg) with that from a combination of granisetron plus methylprednisolone (MPL, 10 mg/kg) for control of emesis and vomiting induced by anticancer drugs in children with cancer. Complete control of emesis and vomiting were achieved in 95% (19/20 cases) of patients receiving the combination compared to 85% (17/20 cases) of patients receiving granisetron alone. There were no clinical toxicities or side effects in either treatment group. These data indicated that the combination of granisetron plus MPL was superior for control of emesis and vomiting in children receiving cytostatic anticancer drugs.     

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.     

Sustained release metoclopramide for prophylaxis of post-operative nausea and vomiting

BACKGROUND: Eclampsia remains a serious complication of pregnancy and childbirth and factors related to morbidity require continued evaluation. DESIGN: Retrospective case-control study on the incidence and outcome of eclampsia. SETTING: A defined total island population over 20 years. METHODS: All centrally collected birth registration returns in Iceland for the years 1972-1991 were reviewed to identify women with the diagnosis of eclampsia, selecting women delivering immediately before and after the eclamptic case as controls. Information from all places where women had delivered was obtained to ensure that no case was missed. Maternity records were reviewed to verify the diagnosis and obtain maternal and neonatal data. RESULTS: Forty women had eclampsia (0.046% of deliveries). The incidence diminished between the decades 1972-81 and 1982-91 (p < 0.05), as did the incidence of eclamptic convulsions before delivery. Eclamptic women were more often primiparous, younger and delivered earlier than controls. Preterm delivery and a low ponderal index were more common among offspring of the eclamptic mothers and the male/female ratio was lower. CONCLUSION: The incidence of eclampsia in the population is falling. Common features related to the condition were confirmed. Severe maternal illness is rare, but the babies often appear growth-retarded and are delivered preterm.     

Effects of granisetron and its combination with dexamethasone on cisplatin-induced delayed emesis in the ferret

1. Granisetron and its combination with dexamethasone for the treatment of delayed emesis following cisplatin (CDDP) administration were investigated using ferrets. 2. CDDP-induced emesis was significantly inhibited in both the granisetron group and the combined granisetron and dexamethasone group during the acute and delayed phase in terms of total emesis, latency to first emesis and duration of emesis. 3. Food and water consumption in the combined group of ferrets was significantly increased as compared with the CDDP control group. 4. 5-Hydroxytryptamine (5-HT) level was increased in the ileum and the 5-hydroxyindole acetic acid (5-HIAA) level was increased in the area postrema of ferrets after 3 days of CDDP administration. It is suggested that the antiemetic activity of granisetron and/or dexamethasone is not related to 5-HT levels in delayed emesis. 5. Both granisetron and its combination with dexamethasone are effective in CDDP-induced emesis, but combination treatment is more effective than granisetron alone for the duration of emesis in the delayed phase.     

A randomized trial of tropisetron in the prophylaxis of nausea and vomiting induced by chemotherapy

Thirty patients receiving cisplation or non-cisplatin (containing cyclophosphamide and adriamycin) chemotherapy were enrolled in a randomized, crossover study comparing the efficacy of single dose of Navoban (tropisetron, 5 mg) and Kytril (granisetron, 3 mg). The effective control of acute vomiting induced by cisplatin was achieved in 95.2% (20/21) of patients receiving Navoban and 90.5% (19/21) in those receiving Kytril. Complele control rate was 71.4% (15/21) in Navoban arm, and 81.0% (17/21) in Kytril arm. Total control of delayed vomiting (day 2-5) was 71.4%-90.4% in Navoban arm, while it was 66.7%-4% in Kytril arm. The effective control of vomiting induced by non-cisplatin drugs was achieved in 9/9 in both arms. It is concluded that both agents are effective in the control of vomiting induced by chemotherapy. They have identical adverse effects and are well tolerated by the patients.     

Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus

BACKGROUND: The Pediatric AIDS Clinical Trials Group Protocol 076 reported a reduction in the rate of perinatal transmission of the human immunodeficiency virus (HIV) from 25.5 percent to 8.3 percent with a three-part regimen of zidovudine given ante partum, intra partum, and to the newborn. We examined the effects of abbreviated zidovudine regimens on perinatal HIV transmission using data from the HIV polymerase-chain-reaction (PCR) testing service of the New York State Department of Health. Pregnant women who received abbreviated regimens rather than the recommended regimens did so because of limited prenatal care or by choice. METHODS: The requisition form used by the PCR testing service included information on the demographic characteristics of the infants and the timing of any perinatal treatment with zidovudine. We also analyzed data on the timing of zidovudine prophylaxis collected by chart review in a subgroup of 454 infants as a means of validating the results in the entire cohort. RESULTS: From August 1, 1995, through January 31, 1997, specimens from 939 HIV-exposed infants who were 180 days of age or younger were submitted for PCR testing. The rates of perinatal HIV transmission varied depending on when zidovudine prophylaxis was begun. When treatment was begun in the prenatal period, the rate of HIV transmission was 6.1 percent (95 percent confidence interval, 4.1 to 8.9 percent); when begun intra partum, the rate was 10.0 percent (3.3 to 21.8 percent); when begun within the first 48 hours of life, the rate was 9.3 percent (4.1 to 17.5 percent); and when begun on day 3 of life or later, the rate was 18.4 percent (7.7 to 34.3 percent). In the absence of zidovudine prophylaxis, the rate of HIV transmission was 26.6 percent (21.1 to 32.7 percent). CONCLUSIONS: These results confirm the efficacy of zidovudine prophylaxis and suggest that there are reductions in the rates of perinatal transmission of HIV even with the use of abbreviated regimens that are begun intra partum or in the first 48 hours of life.     

Levonantradol, a new antiemetic with a high rate of side-effects for the prevention of nausea and vomiting in patients receiving cancer chemotherapy

Levonantradol, a new antiemetic compound pharmacologically related to the cannabinoids, was given to 17 patients who had experienced severe and protracted nausea and vomiting during previous courses of cancer chemotherapy, and to six patients receiving a first course of strongly emetic cytostatic treatment. Eight patients were partially protected from acute gastrointestinal disturbances. Of the 23 patients, 21 exhibited some toxicity, with six patients exhibiting major affective side-effects and 13 patients complaining of pain at the injection site. Levonantradol is an active antiemetic compound. Due to the rate of side-effects observed in our study however, we would not recommend use of this agent as an antiemetic drug.     

An in vitro comparison of three fluoride regimens on enamel remineralization

PURPOSE: Chorioretinal toxoplasmosis can threaten visual function when located in the posterior pole. The aim of this study was to compare the advantages and disadvantage of combination of malocid-sulfadiazine and clindamycin subconjunctivally. METHODS: Two groups of patients affected by unilateral chorioretinal toxoplasmosis were studied. The diagnosis was performed in 77% of cases on acqueous humor analysis. The first group of twenty-six patients was treated with a combination of malocid-sulfadiazine while the second group (seventeen patients) was treated with clindamycin subconjunctivally. Local and general corticosteroids were associated in all cases. Mean follow-up was 19 months in the first group and 16.5 months in the second. RESULTS: Visual acuity was increased in 88.5% of cases in the first group and in 94% of cases in the second group. Cicatrization obtained in both groups was comparably delayed 1.68 months for the first and 1.26 months for the second. Recurrences were rarely observed in the two groups: respectively 8% and 6% of cases. No local and general complication was noted. CONCLUSION: These findings suggest the advantages of subconjunctival clindamycin treatment due to the absence of general hematological toxicity.     

Comparing the effectiveness of behavioral treatment for chemotherapy-induced nausea and vomiting when administered by oncologists, oncology nurses, and clinical psychologists.

72 cancer patients with anticipatory nausea and vomiting (ANV) were randomly assigned to no-treatment control or to systematic desensitization (SD) from 5 behaviorally trained clinical psychologists, 6 clinical oncologists, or 10 oncology nurses. The treatment was effective in reducing ANV and posttreatment nausea and vomiting compared to control patients, with no significant differences in effectiveness found between clinical psychologists and oncology staff. Although medical personnel should not engage patients in psychotherapy or other interventions that cannot be completed successfully, they can treat patients effectively with SD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of ceftibuten once daily and amoxicillin-clavulanate three times daily in the treatment of acute exacerbations of chronic bronchitis

In medical practice, antibiotics are generally given empirically for the treatment of acute exacerbations of chronic bronchitis (AECB). To be effective, antibiotic therapy should be broad in spectrum, and it should also cover the common beta-lactamase-producing pathogens. In this multicenter, randomized, investigator-masked study, 469 patients with AECB were randomized (in a ratio of 2:1) to receive 400-mg oral ceftibuten capsules once daily or 500-mg amoxicillin-clavulanate tablets three times daily for 5 to 15 days. Patients receiving ceftibuten were further divided into those who took the capsule with a meal (fed) and those who took the capsule 1 hour before a meal (fasted). Clinical and microbiologic responses were evaluated after treatment at 0 to 6 days (end of treatment) and 7 to 21 days (follow-up). Overall clinical success was determined by cure/improvement of signs and symptoms of AECB at the end of treatment and at follow-up. Overall microbiologic assessment was graded as eradication, persistence, relapse, reinfection, colonization, superinfection, or unassessable. Tolerability was evaluated by grading observed adverse events. The mean duration of treatment was 10.4 days for patients who received ceftibuten and 10.1 days for patients who received amoxicillin-clavulanate. A total of 252 patients receiving ceftibuten and 117 patients receiving amoxicillin-clavulanate were evaluable for clinical efficacy, and 55 patients were evaluable for microbiologic response. Both treatments improved the signs and symptoms of bronchitis, and overall clinical success rates were equivalent for patients treated with ceftibuten (211 of 252 [84%]) and amoxicillin-clavulanate (93 of 117 [79%]) (95% confidence interval [CI], -4.5% to 13.6%). Overall microbiologic eradication rates were also similar for patients treated with ceftibuten (36 of 37 [97%]) and amoxicillin-clavulanate (12 of 14 [86%]) (95% CI, -5.2% to 21.2%). The most frequently reported treatment-related adverse events were gastrointestinal disturbances, which occurred in 15% (47 of 316) and 24% (36 of 152) of patients treated with ceftibuten and amoxicillin-clavulanate, respectively. No significant difference was observed in the ceftibutenfed and ceftibuten-fasted groups in overall clinical assessments of the clinical efficacy population and safety population. In conclusion, 400 mg oral ceftibuten once daily has a similar clinical success rate to 500 mg amoxicillin-clavulanate three times daily, with a trend toward fewer gastrointestinal side effects, in the treatment of patients with AECB.     

Efficacy of ondansetron in prophylaxis of postoperative nausea and vomiting in patients following infratentorial surgery: a placebo-controlled prospective double-blind study

Competitive PCR was used to monitor the survival of a 520-bp DNA target sequence from a recombinant plasmid, pVACMC1, after admixture of the plasmid with freshly sampled human saliva. The fraction of the target remaining amplifiable ranged from 40 to 65% after 10 min of exposure to saliva samples from five subjects and from 6 to 25% after 60 min of exposure. pVACMC1 plasmid DNA that had been exposed to degradation by fresh saliva was capable of transforming naturally competent Streptococcus gordonii DL1 to erythromycin resistance, although transforming activity decreased rapidly, with a half-life of approximately 50 s. S. gordonii DL1 transformants were obtained in the presence of filter-sterilized saliva and a 1-microg/ml final concentration of pVACMC1 DNA. Addition of filter-sterilized saliva instead of heat-inactivated horse serum to S. gordonii DL1 cells induced competence, although with slightly lower efficiency. These findings indicate that DNA released from bacteria or food sources within the mouth has the potential to transform naturally competent oral bacteria. However, further investigations are needed to establish whether transformation of oral bacteria can occur at significant frequencies in vivo.     

Effect of immunosuppressive drug regimens on acute and chronic murine toxoplasmosis

This study was undertaken to quantify salivary gland parenchymal damage after radioiodine treatment with a standard protective regimen of ascorbic acid. Altogether, 106 patients underwent quantitative salivary gland scintigraphy with 99Tcm-pertechnetate prior to and 3 months after radioiodine therapy. Parenchymal function was quantified by calculating 99Tcm-pertechnetate uptake 13 min post-injection. Patients received 131I doses ranging from 400 MBq to 24 GBq (cumulative). Among the patients who received large doses of 131I, severe parenchymal destruction could be visually analysed as well as quantitatively evaluated. In contrast, after low-dose radioiodine treatment, mild parenchymal impairment was demonstrated by quantitative evaluation only. In conclusion, standardized quantitative salivary gland scintigraphy is essential for the reliable detection of mild parenchymal malfunction. Despite the standard protection regimen using ascorbic acid as a sialogogue, radioiodine therapy induces loss of salivary gland parenchymal function even with low doses of 131I.