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)

During a 4-year period a 28-year-old female had 4 episodes of eosinophilia of over 10,000/mu 1; these episodes were associated with nausea, vomiting, diarrhea, and abdominal pain. On one occasion, she had ascites and pleural effusion which contained numerous mature eosinophils. On each occasion, these attacks disappeared within several weeks without any specific treatment. A diagnosis of eosinophilic gastroenteritis was made. A plasma sample obtained during the eosinophilia generated in vitro eosinophilic colonies when added to granulocyte/macrophage-progenitor (CFU-GM) cultures without exogenous growth factors. Colony formation was inhibited by anti-interleukin-5 (IL-5) antibody but not by antibodies toward IL-3, granulocyte colony-stimulating factor (G-CSF) or GM-CSF. A high plasma interleukin-5 (IL-5) level was noted when measured by enzyme-linked immunosorbent assay, while IL-3, G-CSF, and GM-CSF were undetectable. During remission the plasma gave negative results both for colony formation and IL-5 level. These results indicate that the eosinophilia of this disease is mediated by IL-5.
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PMID:Interleukin-5 in eosinophilic gastroenteritis. 138 Feb 4

Patients may be intolerant of zidovudine for several reasons, the most prominent being hematologic toxicity. In vitro studies demonstrate that zidovudine is toxic to the myeloid and erythroid precursors in the bone marrow; at concentrations of zidovudine near those associated with the optimal antiviral effect in vitro, the proliferative capability of these progenitor cells is reduced 50%-70%. The clinical manifestations of anemia and leukopenia generally are time- and dose-dependent. Strategies for alleviating the hematologic toxicity of zidovudine include the use of hematopoietic growth factors, such as erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor. Myopathy, a recently recognized toxic effect of zidovudine, also appears to be time-dependent. Patients often complain of muscle weakness and discomfort and exhibit an associated elevation in creatine phosphokinase level; dose reduction or discontinuation of therapy generally is required. Some patients have experienced high fever, nausea, and vomiting; however, these effects are unusual and of unclear etiology. The substantial proportion of patients with AIDS or AIDS-related complex receiving zidovudine who experience hematologic or muscular toxicity may benefit from treatment with new antiviral agents, such as dideoxyinosine, with toxicity profiles different from that of zidovudine.
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PMID:Zidovudine intolerance. 220 Oct 71

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 24-hour infusion, and carboplatin have activity in advanced non-small cell lung cancer (NSCLC) and ovarian cancer. Two dose-finding studies were initiated to identify the optimal doses for the paclitaxel/carboplatin combination when paclitaxel is given in a 3-hour infusion. The fact that the pharmacologic interaction between paclitaxel and cisplatin increases the toxicity of paclitaxel when cisplatin is given before it also prompted an investigation of the influence of drug sequence on toxicity and pharmacokinetics in the NSCLC trial. Thirty-three patients with advanced NSCLC and 11 with advanced ovarian cancer previously untreated by chemotherapy have been enrolled to date. In the NSCLC trial escalating doses of paclitaxel were given in combination with a fixed carboplatin dose of 300 mg/m2, while both drugs were escalated in the ovarian cancer study. In both studies paclitaxel was infused over 3 hours and carboplatin over 30 minutes, and cycles were repeated every 4 weeks. The most frequent side effect has been neutropenia, although this did not result in any infectious episodes. Alopecia and mild emesis also have been frequently encountered. Mild skin reactions have been reported in a few patients. Bone pain and myalgia occur more frequently at the highest paclitaxel doses. No difference in toxicity has been observed thus far between the two drug sequences in the NSCLC study. Both studies are still accruing patients as the maximum tolerated doses of paclitaxel in combination with carboplatin have not yet been reached (carboplatin 300 mg/m2 with paclitaxel 175 mg/m2 in the NSCLC study; carboplatin 400 mg/m2 with paclitaxel 150 mg/m2 in the ovarian cancer study). An investigation of maximum tolerated doses with granulocyte colony-stimulating factor support is planned thereafter.
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PMID:Preliminary results of two dose-finding studies of paclitaxel (Taxol) and carboplatin in non-small cell lung and ovarian cancers: a European Cancer Centre effort. 793 61

Despite 20 years of chemotherapy trials in advanced NSCLC, optimal regimens leading to complete remissions have not been identified. The decision to treat a patient who has inoperable advanced NSCLC must take into account the toxicity of the chemotherapy. The toxicities most often reported are myelosuppression and emesis; however, these trials were performed before the use of colony-stimulating factors (ie, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor) and serotonin antagonists (ie, ondansetron). Granulocyte colony-stimulating factor has been shown to shorten the duration of neutropenia and thus decrease the incidence of confirmed infections. Colony-stimulating factors also may allow significant escalation of the dose of chemotherapy. Ondansetron has been shown to ameliorate cisplatin-induced emesis better than other antiemetics. The performance status of a patient has been noted to be a predictor for survival, as well as response to therapy, and this should also be taken into consideration when deciding to treat a patient with advanced inoperable NSCLC. Ideally, patients with stage IV NSCLC should be placed on investigational therapy protocols to identify optimally active combinations of agents. One approach to the patient with inoperable NSCLC who is ineligible for a trial, or who does not wish to participate in a trial, is to offer chemotherapy soon after diagnosis, as patients in this category are likely to be less symptomatic and have optimal performance status. A platinum-containing regimen would seem to be the most reasonable regimen in such a patient. It is hoped that ongoing trials in suitable candidates will lead to the identification of more consistently active agents to deal with this devastating disease.
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PMID:Chemotherapy outcomes in advanced non-small-cell lung carcinoma. 839 89

A phase II trial was performed to evaluate the efficacy and tolerance of vinorelbine (VNB), mitomycin C (MMC), and recombinant human granulocyte colony-stimulating factor (G-CSF) in advanced breast cancer. Between October 1992 and July 1994, 55 patients entered this trial. Nine patients had locally advanced disease and 46 had distant metastases, including 14 who had received previous palliative chemotherapy with (n = 9) or without anthracyclines (n = 5). Therapy consisted of VNB 40-50 mg m(-2) diluted in 250 ml saline infused over 30 min every 3 weeks, and MMC 15 mg m(-2) administered by intravenous bolus injection every 6 weeks. G-CSF was given at 5 microg kg(-1) day(-1) subcutaneously from days 2 to 7 following each cytotoxic drug administration. Treatment was continued in case of response or stable disease for a total of six courses. The overall response rate was 73% for all 55 patients (95% confidence interval, 59-84%), including 12 (22%) complete response (CR) and 28 (51%) partial response (PR); 13 patients (24%) had stable disease (SD), and only two (4%) progressed. All nine patients with locally advanced disease were rated responsive (two pCR, seven PR) and underwent surgery with curative intent. Eight out of nine remain disease free after a median observation period of 18 months (range, 13.5-28 months). Among the 32 previously untreated patients with metastatic disease, nine (28%) achieved CR, 15 PR (47%), seven SD (22%) and one PD (3%). Second-line chemotherapy with this regimen resulted in 7/14 (50%) objective remissions (one CR, six PR), six had SD and one PD. The median time to progression was 12 months (range, 2-24+ months) in previously untreated patients with disseminated disease, and 6.0 months (range, 2-22 months) in those who had failed prior chemotherapy. After a median follow-up time of 20 months, 24 patients with distant metastases are still alive with disease; median survival has not been reached yet. The dose-limiting toxicity was myelosuppression: six (11%) and ten patients (18%) had World Health Organization grade 3, and eight (14%) and nine patients (16%) had grade 4 leucopenia and granulocytopenia respectively. Severe (WHO grade 3) non-haematological toxicities included nausea/vomiting in 7%, constipation in 9%, peripheral neuropathy in 5%, infectious episodes in 7%, phlebitis due to drug extravasation in 5%, alopecia in 9%, and acute reversible pulmonary toxicity in 11%. Our data suggest that vinorelbine, mitomycin C plus G-CSF has an excellent anti-tumour activity in advanced breast cancer, probably superior to most other available combination chemotherapy regimens. This combination does not seem to present significant cross-resistance with previous CMF or anthracycline regimens. Apart from reversible, acute pulmonary toxicity, a rare adverse reaction that had previously been described for VNB, as well as the combination of natural vinca alkaloids with mitomycin C, and few episodes of grade 3 neurotoxicity (all of which occurred at the initial 50 mg m(-2) VNB dose level), the tolerance of this regimen seems acceptable and justifies further evaluation in front-line and salvage therapy of advanced breast cancer.
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PMID:Effective treatment of advanced breast cancer with vinorelbine, mitomycin C plus human granulocyte colony-stimulating factor. 893 53

Recently, a randomized study conducted by the Gynecologic Oncology Group (GOG 111) demonstrated that, given by a 24-hour infusion, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is superior to combination cisplatin/cyclophosphamide in previously untreated patients with advanced ovarian cancer. This combination, however, necessitates hospitalization. Combination paclitaxel/carboplatin would be expected to induce fewer nonhematologic side effects but may be more myelotoxic. Thus, we started a phase I dose-escalation study to determine the maximal tolerated dose of paclitaxel given as a 3-hour infusion in combination with carboplatin, both drugs administered every 21 days. The paclitaxel dose was escalated by increments of 25 mg/m2, starting at 135 mg/m2 (level 1), 160 mg/m2 (level 2), 185 mg/m2 (level 3), and 210 mg/m2 (level 4). Carboplatin was administered to achieve an area under the concentration-time curve of 5, using the Calvert formula For study levels 5 and 6, the carboplatin dose was targeted at area under the concentration-time curves of 6 and 7.5, respectively, and was combined with a fixed paclitaxel dose of 185 mg/m2. Thirty previously untreated patients with stage IIC to IV ovarian cancer were enrolled. Nonhematologic toxicity, including nausea/vomiting and arthralgia/myalgia, was mild. Across all dose levels, a total of 16 patients developed peripheral neurotoxicity (World Health Organization grades 1 and 2). At dose level 5, one patient experienced reversible grade 4 neurotoxicity. Neutropenia was the principal dose-limiting hematologic toxicity. During 33 (31%) of 106 courses, World Health Organization grade 4 neutropenia was observed. Granulocyte colony-stimulating factor was required in only 7.6% of courses. Thrombocytopenia was less than that expected when carboplatin is given alone. Clinical responses were observed in eight of 14 patients, for an overall response rate of 57%. The combination of carboplatin plus paclitaxel was found to be an active regimen. This trial demonstrates that carboplatin dosed by the Calvert equation and 3-hour paclitaxel can be combined safely at full therapeutic doses for six or more courses in patients with advanced epithelial ovarian cancer.
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PMID:Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer: a phase I trial. 904 30

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be one of the most active drugs in the treatment of advanced head and neck cancer. The maximum tolerated dose of paclitaxel in combination with carboplatin is currently being evaluated in phase I/II studies. We designed a phase II study to evaluate the activity and acute and cumulative toxicity of this combination in patients with recurrent or metastatic cancer of the head and neck. Chemotherapy consisted of paclitaxel 200 mg/m2, given as a 3-hour infusion, and carboplatin dosed to an area under the concentration-time curve of 7 mg x min/mL, administered every 28 days. Granulocyte colony-stimulating factor (5 microg/kg) also was given on days 2 to 12 of each cycle. At the time of this report, 41 patients had entered this study. Primary sites included the nasopharynx (10 patients), larynx (18), oral cavity (three), oropharynx (six), hypopharynx (three), and unknown (one). Among 25 evaluable patients with non-nasopharyngeal cancer, there were two complete responses and three partial responses, for an overall response rate of 20% (95% confidence interval, 4% to 36%). Among eight evaluable patients with nasopharyngeal cancer, four achieved a complete response and two a partial response. Grade 3 to 4 toxicities included anemia (2.5%), leukopenia (7.5%), thrombocytopenia (5%), vomiting (5%), stomatitis (2.5%), and infection (5%). These preliminary data indicate that the combination of paclitaxel and carboplatin is active against advanced head and neck cancer, particularly when used in the treatment of nasopharyngeal cancer.
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PMID:Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. 904 40

We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF) priming, and CD34+ enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of cisplatin 250 mg/m2, etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (> or = 7.5 x 10(8) nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34+ enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day -2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 micrograms/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 micrograms/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 x higher numbers of CD34+ cells in the PBSC product than the same total dose given once a day (P = .002). Reinfusion of 25% of unselected PBSC on day -2 (median, 2.26 x 10(8)/kg nucleated cells [range, 1.7 to 3.3 x 10(8)/kg]) with the remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to > or = 500/microL when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P = .0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P = not significant). Split schedule reinfusion of CD34(+)-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34(+)-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P < or = .005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of approximately 2.26 x 10(8)/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34+ cell population. Sustained hematopoietic recovery can also be achieved with CD34(+)-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34+ cell yield in the leukapheresis product. Whether even earlier "sacrificial" reinfusion of approximately 2 x 10(8)/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation.
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PMID:Effect of CD34+ selection and various schedules of stem cell reinfusion and granulocyte colony-stimulating factor priming on hematopoietic recovery after high-dose chemotherapy for breast cancer. 905 32

Preliminary results of this ongoing phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus epirubicin administered as first-line treatment to women with metastatic breast cancer indicate encouraging response rates and no severe toxicity. Among the 57 patients admitted to this study, 52% had received prior adjuvant chemotherapy (85% with cyclophosphamide/methotrexate/5-fluorouracil), 46% had received radiotherapy, and 30% had received both forms of therapy; 63% of patients were postmenopausal, mainly with poorly differentiated tumors, and 80% presented with > or = 2 metastatic sites. Epirubicin 60 mg/m2 was administered intravenously as a 1-hour infusion followed by paclitaxel 175 mg/m2 infused over 3 hours. Standard premedication was given. Granulocyte colony-stimulating factor support was not used. Neutropenia was evident in 72% of cycles but was not severe. Instances of anemia and thrombocytopenia were rare. Alopecia was universal. All nonhematologic toxicity observed was mild or moderate (peripheral neuropathy, myalgia, nausea, vomiting World Health Organization toxicity grade < 2). At this time, 41 patients are currently evaluable for response, complete and partial remission are evident in seven and 21 patients, respectively. The overall response rate so far is 68%. An additional 12 patients show evidence of stable disease, and one has shown disease progression. Paclitaxel is considered a promising new drug in the adjuvant treatment of patients with metastatic breast cancer. Combining it with epirubicin allows safe administration with no evidence of severe cardiotoxicity. The incidence of adverse cardiac events was much lower than that observed with combinations of paclitaxel and doxorubicin.
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PMID:Preliminary results of a phase II study of epirubicin and paclitaxel as first-line treatment in patients with metastatic breast cancer. 907 34

This phase I study was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with standard doses of cisplatin and etoposide for patients with untreated, extensive-stage small cell lung cancer. Secondary objectives were to determine the toxicities, response rate, response duration, and overall survival in this cohort. Twenty-four patients were enrolled into four dose levels. All patients received a fixed dose of cisplatin at 80 mg/m2 intravenously (IV) on day 1. The first group received etoposide 50 mg/m2 IV on day 1 and 100 mg orally on days 2 and 3, while all subsequent groups received etoposide 80 mg/m2 IV on day 1 and 160 mg/m2 orally on days 2 and 3. The paclitaxel starting dose was 135 mg/m2 IV over 3 hours and escalated to 175 mg/m2 and 200 mg/m2. Cycles were repeated every 21 days for a maximum of six cycles. Granulocyte colony-stimulating factor was not given prophylactically, but was allowed in subsequent cycles according to American Society of Clinical Oncology guidelines. Nineteen patients were evaluable for toxicity and 18 patients were evaluable for response. Myelosuppression was the major toxicity, with grade 4 neutropenia occurring in 18 of 19 patients (95%), but febrile neutropenia was uncommon and developed in four of 19 patients (21%). Dose-limiting peripheral neuropathy was observed at a paclitaxel dose of 200 mg/m2. Grade 4 nausea/vomiting and diarrhea were also noted at this dose level. Four patients had complete responses (22%) and 13 patients had partial responses (72%). The overall response rate was 94%, with a median survival of 11 months and a 2-year survival rate of 19%. This three-drug combination of paclitaxel with cisplatin and etoposide is highly active with acceptable toxicity. Neurotoxicity was dose limiting at 200 mg/m2 paclitaxel. Neutropenia was frequent but was not associated with significant morbidity. The recommended doses for future clinical trials are paclitaxel 175 mg/m2 IV over 3 hours on day 1 with cisplatin 80 mg/m2 IV on day 1 and etoposide 80/160 mg/m2 IV on day 1 and orally on days 2 and 3. Growth factor support should be used according to American Society of Clinical Oncology guidelines.
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PMID:A phase I study of cisplatin, etoposide, and paclitaxel in small cell lung cancer. 933 Nov 40


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