Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cisplatin has played a major role in the treatment of germ cell tumors. However, it causes renal damage, severe nausea and vomiting. It is also neurotoxic and ototoxic. Carboplatin is an analog of cisplatin which, does not cause renal damage at therapeutic doses. It is not neurotoxic or ototoxic and it produces less gastrointestinal toxicity than cisplatin. We used carboplatin alone as an initial chemotherapy in a 36-year-old man with stage IIB seminoma. Following left radical orchiectomy the patient received 4 courses of carboplatin chemotherapy. After the first course of chemotherapy, tumor markers (LDH, beta-HCG) returned to the normal range. After 4 courses, the size of the retroperitoneal metastases was significantly reduced. The toxicity of 4 courses of carboplatin chemotherapy was generally milder than that of cisplatin-based combination chemotherapies such as PVB or VAB-6. There were no episodes of septicemia, thrombocytopenic bleeding or renal deterioration. The patient did not suffer from alopecia, neuropathy, symptomatic hearing loss, severe nausea or vomiting. Nine months after the completion of carboplatin chemotherapy, the patient remains well and free from disease progression. This case strongly suggests that single agent carboplatin therapy could be an effective and less-toxic treatment for advanced seminoma.
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PMID:[A case of advanced seminoma treated effectively with single agent carboplatin therapy]. 156 62

60 patients with advanced carcinomas of the oropharynx and hypopharynx underwent chemotherapy, either with 5-FU/Cisplatin (n = 30) or with 5-FU/Carboplatin (n = 30). The remission-rates (complete and partial remissions) were comparable in both groups. The rate of complete remissions, however, was statistically significant higher in the cisplatinum group (6 patients) than in the carboplatinum group (1 patient). 2 patients of the 5-FU/Cis-group and 4 patients of the 5-FU/Carbo-group developed a progressive disease during chemotherapy. Statistically significant differences were found in the nephrotoxic and myelotoxic side effects between both therapy groups: nephrotoxic side effects were more frequent in the 5-FU/Cis-group, whereas myelotoxic side effects occurred mainly in the 5-FU/Carbo-group. The chemotherapy with 5-FU/Carboplatin was better tolerated by the patients than in the 5-FU/Cisplatinum-group. In the 5-FU/Carbo-group especially a lower rate and severity of loss in weight, nausea, vomiting, alopecia and mucositis/stomatitis was observed. No statistically significant differences were found in ototoxic side effects between both groups.
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PMID:[Antineoplastic effectiveness and unwanted side effects of polychemotherapy of extensive oro- and hypopharyngeal cancers--results of a prospective therapy study with 5-FU/cisplatin versus 5-FU/carboplatin]. 161 47

We have monitored the expression of c-fos protein in the medulla oblongata of the ferret, using immunocytochemistry, to identify the brainstem pathways involved in the mediation of nausea and vomiting caused by the antineoplastic drug cisplatin. Cisplatin administration resulted in c-fos-like immunoreactivity (FLI) in the area postrema, the nucleus of the solitary tract, and in scattered cells within the ependymal lining of the fourth ventricle. Unilateral cervical vagotomy greatly reduced FLI in the ipsilateral nucleus of the solitary tract but did not significantly affect reactivity in the contralateral solitary tract nucleus or in the area postrema. Pretreatment of the animals with the 5-HT3 antagonist granisetron (BRL 43694) abolished the retching and vomiting caused by cisplatin and markedly reduced the cisplatin-evoked FLI in the nucleus of the solitary tract; treatment with this drug had no significant effect on cisplatin-evoked FLI in the area postrema. The results suggest that cisplatin induces c-fos gene expression in the nucleus of the solitary tract by an action involving vagal afferent pathways and also by a vagally independent, direct action on the area postrema. The anti-emetic 5-HT3 antagonist drug granisetron mimicked the effect of vagotomy on c-fos protein induction suggesting that it may act via 5-HT3 receptors known to be associated with vagal afferent terminals. The FLI seen in the area postrema was neither vagally dependent nor was it abolished by granisectron.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cisplatin-evoked induction of c-fos protein in the brainstem of the ferret: the effect of cervical vagotomy and the anti-emetic 5-HT3 receptor antagonist granisetron (BRL 43694). 166 10

The efficiency of cis Platin (DDP) alone and in combination with Adriamycine (ADM) and Cyclophosphamid (CTX) were evaluated in a prospective randomized trial containing 173 pat. suffering from advanced ovarian cancer (FIGO III/IV). Therapeutic schedule and results: (table; see text) The most side effects concerned vomiting (WHO Grad 2) in 90%, nausea (WHO Grad 2) in 95% and alopecia in 50% out of all pat.
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PMID:[Effectiveness of cisplatin alone and in combination within the scope of primary therapy of ovarian cancer. Results of a prospective multicenter study]. 169 49

Many chemotherapeutic agents have been evaluated during the last 40 years and some have now an established place in the management of malignant disease. However these agents have a level of toxicity well above any other group of drugs. Chemotherapeutic agents do not discriminate between normal and neoplastic tissue. Chemotherapeutic regimens that are toxic to rapidly dividing malignant cells, are liable to be particularly harmful to lymphoid tissues, bone marrow and the epithelium of the gastrointestinal tract. The side effects due to chemotherapy are classified as immediate, early, delayed and late. Immediate side effects are those that may occur within the first 24 hours of treatment. The most common immediate side effect is nausea and vomiting, due to direct central effect on the vomiting center of the brain. Cisplatin and nitrogen mustard are particularly prone to this complication. The antiemetics usually used are metoclopramide, domperidone and steroid. The efficacies of these drugs are not so good for nausea and vomiting due to cisplatin administration, however several blockades against serotonin M-receptor recently developed are quite effective to nausea and vomiting of chemotherapeutic regimens including cisplatin. Early side effects commence within about one month of therapy. The most common is bone marrow toxicity and can occur after therapy with the vast majority of anticancer drugs. The relative importance of leukopenia and thrombocytopenia vary between the drugs and their route of administration. Recently, hematopoietic cytokines, such as granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSP) have been introduced to granulocytopenia developed by cancer chemotherapy. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy and marked efficacy on infection in granulocytopenic patients were observed. In addition to this, autologous bone marrow transplantation after chemotherapy has been described in patients with solid tumors.
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PMID:[Palliative therapy in cancer. 5. Side effects by anticancer drugs and their treatments]. 169 55

Cisplatin, bleomycin, and mitomycin-C were used to treat 25 patients with recurrent squamous cell carcinoma of the cervix. Six patients had a partial response, yielding a total response rate of 27%. Nine patients had stable disease. The median survival for the whole group was 30 weeks. The median survival for responders was 32 weeks. The median progression free interval for the whole group was 12 weeks and the median progression-free free interval for responders was 14 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cisplatin, bleomycin, and mitomycin-C has modest effectiveness in the treatment of recurrent squamous cell carcinoma of the cervix, but represents no improvement over single-agent chemotherapy.
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PMID:A phase II evaluation of cisplatin, bleomycin, and mitomycin-C in patients with recurrent squamous cell carcinoma of the cervix. 170 24

Cisplatin is an effective antineoplastic agent that causes severe vomiting due to unknown mechanism. The ferret, an animal model useful in the determination of emetic activity, was used to clarify the emesis-related biochemical and histopathological changes that were induced by cisplatin. Cisplatin (5 to 10 mg/kg) was administered intraperitoneally and a 7-10 mg/kg i.p. dose evoked dose-dependent emesis in the ferret. Almost all cisplatin-vomiting episodes occurred within a 6 hour observation period. All ferrets receiving cisplatin in this study died within 3-5 days. Significant increases in ileal mucosal levels of serotonin and norepinephrine were observed in cisplatin-treated ferrets. There were no significant changes in the levels of serotonin and dopamine in the gastric mucosa. Also, karyorrhexis was observed in the epithelial cells of the ileum and in the lymph follicles of the spleen of cisplatin-treated ferrets. These significant biochemical and pathological changes in the ileum may play an important role in cisplatin-induced emesis.
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PMID:Emesis-related biochemical and histopathological changes induced by cisplatin in the ferret. 170 1

Isolated segments of the guinea-pig small intestine were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Release of acetylcholine from isolated superfused intestinal segments was determined as outflow of [3H]radioactivity from preparations preincubated with [3H]choline. Cisplatin (3 microM) increased the outflow of 5-HT and 5-HIAA by about 90%. At 30 and 100 microM cisplatin decreased the outflow of 5-HT and its metabolite by 40%-50%. The stimulatory effect of cisplatin was consistently observed only when the bicarbonate-phosphate buffer of the Tyrode's solution was replaced by HEPES-buffer. The stimulatory effect of cisplatin was abolished in the absence of extracellular calcium or presence of tetrodotoxin (1 microM). The stimulatory effect of cisplatin was also prevented by hexamethonium (100 microM) or scopolamine (100 nM). The 5-HT3 receptor antagonists ondansetron and ICS 205-930 in concentrations as low as 1 pM also abolished the stimulatory effect of cisplatin. The 5-HT3 receptor antagonist MDL 72222 prevented the stimulatory effect of cisplatin only at a concentration of 1 microM. None of the 5-HT3 receptor antagonists alone significantly altered the outflow of 5-HT and 5-HIAA. Cisplatin (3 microM) enhanced the outflow of [3H]radioactivity from intestinal segments and caused longitudinal muscle contractions that were abolished by 100 nM scopolamine. In conclusion, cisplatin, at concentrations which occur during anti-cancer therapy in humans and induce emesis, increases the release of 5-HT from the enterochromaffin cells of the small intestine of the guinea-pig.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cisplatin increases the release of 5-hydroxytryptamine (5-HT) from the isolated vascularly perfused small intestine of the guinea-pig: involvement of 5-HT3 receptors. 171 32

A total of 248 analyzable patients with Stages III-IV ovarian epithelial cancer (114 with and 134 without prior chemotherapy) were randomized to one of four cisplatin (DDP)-hexamethylmelamine (HMM) regimens. In each, HMM, 200 mg/m2 was given orally daily on days 8-21 of each 21-day cycle. DDP was given i.v. on Day 1 at a dose of 37.5 mg/m2 (regimens A and B) or 75 mg/m2 (regimens C and D). In addition, since pyridoxine administration has been reported to reduce the neurotoxicity of HMM, that agent was given at a dose of 300 mg/m2 orally on Days 1-21 in regimens B and D. Randomization was stratified for performance status (0-1, 2-3) and largest tumor diameter at entry (greater than 2- less than or equal to 10 cm, greater than 10 cm) for previously untreated patients, and for performance status and time from initial diagnosis to entry on study (less than or equal to 1 year, greater than 1 year) for previously treated patients. The overall response rate (PR + CR) was 54%, with 25% of patients achieving a complete response. The 61% response rate with the higher dose DDP regimens was significantly greater than the 47% response rate with the lower dose regimens (p = 0.031). Multivariate analysis identified higher DDP dose, age less than 60 years, no prior chemotherapy, small tumor bulk and favorable tumor grade as significant prognosticators for response. The overall median response duration was 8.3 months (range 1-70 months). Prior chemotherapy, pyridoxine administration, recent diagnosis, and large tumor size were identified by multivariate analysis as factors adversely affecting response duration. Patients treated with the higher dose DDP regimens had more severe nausea, vomiting, and neurotoxicity. This study demonstrates that the combination of DDP + HMM is an effective regimen for advanced ovarian carcinoma that yields response rates comparable to other more complex regimens, and that there is a dose-response relationship for DDP in ovarian cancer. Although pyridoxine administration significantly reduced neurotoxicity, its adverse effect on response duration suggests that the agent should not be administered with DDP or HMM. The mechanism by which pyridoxine may unfavorably affect response duration deserves further investigation.
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PMID:Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. 173 9

Combination chemotherapy with Cyclophosphamide, Adriamycin and Cisplatin (CAP) is one of the most effective chemotherapies for ovarian cancer. Severe vomiting induced by this treatment may cause a disorder of the serum electrolytes. Severe hyponatremia was observed in one patient who complained of convulsions and unconsciousness. Accordingly we studied the disorder of serum electrolytes in 158 courses of CAP treatment (44 patients) during the five years from 1984 to 1988. The serum electrolytes were influenced by the amount of vomiting in this study. Consequently frequent examination of serum electrolytes is necessary during this treatment.
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PMID:[Disorder of serum electrolytes following CAP therapy]. 174 61


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