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)

On the basis of results obtained with oral idarubicin administration in breast cancer, which have shown an established antitumor activity in approximately 28% of cases, this compound was combined with cyclophosphamide (also given orally) in postmenopausal patients with an unknown or negative steroid receptor status. The study comprised 45 untreated patients out of which 44 were evaluable for response and toxicity. The mean age was 62.5 years (range 51-75). The majority of patients had soft tissue (24) and visceral organ (17) metastases. Idarubicin was administered in one oral daily dose of 45 mg/m2 on day 1; the oral cyclophosphamide dose was 200 mg/m2 daily on days 3, 4, 5 and 6. An objective response to treatment was observed in 41% of patients (18/44, 95% confidence interval 28-56%). Complete remission (lung) was observed in 2 patients (5%), while 16 patients achieved a partial response. Eleven patients showed no change, while 15 patients progressed. A particularly good response was obtained in soft tissue metastases (54%, 13/24) while in visceral organs a response was achieved in 31% of patients (5/16). The remissions lasted 2-14 months (median 7 months), and median survival was 14+ months. Toxicity was mild and the treatment well tolerated. Grade I/II leukopenia was observed in 24% of patients (median WBC nadir 3,100); there were no signs of cardiotoxicity. Grade I and II alopecia was observed in 75% of patients: nausea/vomiting were present in 73% of cases. The results of this study indicate that oral administration of idarubicin and cyclophosphamide produces a valuable antitumorigenic effect in postmenopausal breast cancer patients, particularly in soft tissue metastases. Further randomized studies will be needed to evaluate this treatment approach.
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PMID:Combination of idarubicin and cyclophosphamide administered orally in untreated postmenopausal breast cancer patients. A phase II study. 199 44

A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 months (range, 1-15 months) and median survival amounted to 13 months (range, 2-20 months). Leucopenia (grade 2 or 3) was seen in 14 patients on day 21 of the cycle. A subset of nine patients underwent blood counts on day 10, when all had marked neutropenia (less than 1 x 10(9)/l). Other toxicity was frequent and included nausea/vomiting (80%), alopecia (95%) and stomatitis (35%). Five patients showed a significant fall in cardiac output, but this reverted to normal after treatment. Epirubicin should have a role in the development of high-dose regimens for the treatment of advanced breast cancer.
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PMID:High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study. 199

Due to the favourable results previously obtained with cisplatin in breast cancer (54% response rate), we studied a second-generation platinum analogue, carboplatin, in patients with previously untreated breast cancer. A total of 20 patients were entered in the study and all were evaluable. The median age was 57 years and all patients were in menopause. Karnofsky scores of 80-100 and 40-70 were registered in 14 and 6 cases, respectively. The predominant metastatic site was soft tissue in 12 subjects, visceral organs in 5 and bone in 3; 14 patients had greater than 2 metastatic sites. Carboplatin was given i.v. at a dose of 400 mg/m2 on day 1, with a 3-week rest period. In 13 patients who did not respond or whose disease recurred after carboplatin treatment, the CMFVP, CAP or FAC regimen was given as second line treatment. Carboplatin activity was observed in 4 patients [2 complete remissions (CRs) and 2 partial responses (PRs)], for a response rate of 20% (4/20); the 2 PRs were observed in soft tissue and bone and the 2 CRs, in lung, liver and bone. Remission lasted 2-10 months (mean, 4 months). CMFVP given as second-line chemotherapy to 13 patients produced 7 PRs (7/13, 54%). Toxicity was moderate, producing no drug-related deaths. Anemia (grade I-II) was recorded in seven patients; grade I-II leukopenia, in six; and grade III-IV leukopenia in two (median leukocyte nadir, 1,600/mm3). Thrombocytopenia was observed in three cases (grades I, II and III; median platelet nadir, 47,800/mm3). Unpleasant nausea/vomiting was pronounced (12 cases of grade III-IV) in 19 subjects. There were no cases of neuro- or nephrotoxicity. Due to permanent myelosuppression, no more than five cycles could be given. Our study showed that, unlike cisplatin, carboplatin given at a dose of 400 mg/m2 has low antitumorigenic activity in breast cancer patients and produces pronounced myelotoxicity. Additional first-line chemotherapy studies using carboplatin are needed to define the antitumorigenic activity of this platinum analogue.
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PMID:Carboplatin activity in untreated metastatic breast cancer patients--results of a phase II study. 199 4

Forty-six women with breast cancer treated with adjuvant FAC (fluorouracil, doxorubicin and cyclophosphamide) entered a multicenter, randomized, double-blind, cross-over trial in which thiethylperazine (T) (6.5 mg p.o every 8 h x 3 days) plus methylprednisolone (MP) (250 mg i.v. x 2 doses) was compared with thiethylperazine plus placebo. Forty-four patients were evaluable for efficacy. T + MP was significantly better in reducing vomiting (p less than 0.01) and nausea (p less than 0.02). The complete protection rate against vomiting was 36% for T + MP compared to 18% for T + placebo, and the percentage of nausea grades 0 + 1 (none or slight) was 59% and 27% respectively. The patient preference after cross-over was strikingly in favor of T + MP (70% versus 13%) (p less than 0.001). The most important side-effects of T + MP were facial flushing (22%) and euphoria (27%). Other side-effects, such as dryness of the mouth and sedation, were common after both treatments. In conclusion, the study suggested that T + MP is superior to T alone in protecting from nausea and vomiting induced by FAC.
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PMID:The antiemetic efficacy of thiethylperazine and methylprednisolone versus thiethylperazine and placebo in breast cancer patients treated with adjuvant chemotherapy (fluorouracil, doxorubicin and cyclophosphamide). A randomized, double-blind, cross-over trial. 203 44

Fifty-three breast cancer patients receiving adjuvant chemotherapy entered a double-blind randomized trial of lorazepam 2.5 mg orally prior to chemotherapy and repeated after 12 hours (Arm A) versus placebo (Arm B) with methylprednisolone (MPN) 375 mg in 3 equal doses: 125 mg i.v. prior to chemotherapy and repeated i.m. 6 and 12 hours later. Adjuvant therapy with 5-fluorouracil 600 mg/m2, 4'-epi-doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 (FEC) day 1 was alternated every 21 days with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2 (CMF) day 1 for a total of 12 courses. The majority of patients experienced greater than or equal to 5 emetic episodes with FEC therapy (Arm A = 52%; Arm B = 55%). Mild and moderate nausea were reported by 60% and 68% of patients in Arms A and B, respectively. With CMF therapy complete control of emesis was observed in 33% (Arm A) and 35% (Arm B) of patients. The addition of lorazepam did not improve results either with FEC or CMF. Sedation was experienced by 86 to 92% of patients treated with lorazepam and amnesia was observed in 48-50% of cases. FEC therapy must be considered a highly emetic regimen and antiemetic therapy planned accordingly.
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PMID:Double-blind randomized trial of lorazepam versus placebo with methylprednisolone for control of emesis due to non-cisplatin containing chemotherapy. 209 Jul 73

Cytostatics, besides having a desired therapeutic effect on the tumor, also cause side effects which are sometimes a limiting factor in their application. We have observed the type and intensity of side effects of cytostatic therapy suffered by patients with breast cancer during postoperative period (after radical mastectomy) 28 patients have been treated by CMF protocol (cyclophosphamide, methotrexate, 5-fluorouracil) 29 patients by FAC protocol (5-fluorouracil, adriamycin cyclophosphamide) 31 patients by Cooper protocol (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednizon). The patients have been under observation during a six-months period, while they have been submitted to the adjuvant chemotherapy. On the basis of the results obtained, it can be concluded that CMF protocol turned to be best tolerated. Protocol CMF was to a much lesser extent cause to alopecia, paresthesia, vomiting, urogenital disorders as componed to FAC and Cooper protocols. For that reason the adjuvant chemotherapy for patients with breast cancer should start with the CMF protocol, while FAC and Cooper protocols should be saved for the second line of treatment in case of unfavourable reaction to the CMF protocol.
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PMID:[The most frequent side effects of adjuvant chemotherapy in patients with breast carcinoma]. 209 70

One hundred and sixty-six patients with advanced breast cancer previously not treated with chemotherapy for metastatic disease were randomly allocated to 20 mg Adriamycin i.v. weekly (Awkly) as bolus injection or 50 mg 4-epidoxorubicin biweekly over a 3-h infusion time (EPIbiwkly). Of the 149 patients evaluable for response, the response rate was 36% for Awkly vs. 22% for EPIbiwkly (P = 0.10). There was no difference in response duration or survival. The main difference between the two regimens was in toxicity. Seventy per cent of Awkly patients virtually had no side-effects vs. 15% in the EPIbiwkly group. Significant differences in favour of Awkly were observed both for nausea/vomiting and alopecia.
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PMID:Weekly Adriamycin vs. 4-epidoxorubicin every second week in advanced breast cancer. A randomized trial. The Norwegian Breast Cancer Group. 213 77

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.
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PMID:A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy. 214 Aug 54

The control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem. In this randomized, double-blind, placebo-controlled study, we evaluated the effect of serotonin S3 receptor blockade with ondansetron (GR 38032F) on the prevention of nausea and vomiting induced by cyclophosphamide-containing chemotherapy. Cyclophosphamide was given in doses of 500 to 600 mg/m2 and ondansetron as three intravenous (IV) doses of 0.15 mg/kg. Most patients had breast cancer. Cyclophosphamide was given in combination with doxorubicin (65% of patients) or with fluorouracil (85% of patients: 50% with Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] and 35% with methotrexate). All placebo-treated patients experienced vomiting, whereas 70% of patients treated with ondansetron did not vomit (P = .008). Median nausea scores were 8 mm on ondansetron and 65 mm on placebo (P less than .001). Seventy percent of patients treated with ondansetron retained their normal appetite, compared with 10% of placebo patients. Adverse events occurred in six placebo patients and one ondansetron patient. Diarrhea and headache were the most common events, both occurring more frequently in the placebo group. There were no extrapyramidal reactions, and the only significant biochemical change occurred in a placebo-treated patient. These results suggest that serotonin S3 receptor antagonists represent a novel, effective, and safe mode of therapy for nausea and emesis induced by cyclophosphamide-containing chemotherapies. In addition, our observations are compatible with the view that serotonin, acting on S3 receptors, mediates the nausea and emesis occurring after cyclophosphamide chemotherapy.
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PMID:Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens. 182 40

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses greater than or equal to 40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBG rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses greater than or equal to 60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations greater than 24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.
Breast Cancer Res Treat 1990 Aug
PMID:Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. 214 80


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