Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A combined therapy using miconazole (MCZ) and G-CSF was evaluated in clinical patients who developed deep-seated mycoses and fever of unknown etiology following chemotherapy for malignant gyneco-obstetrical tumors. 1. Combined administration of 100 to 250 micrograms/day of G-CSF, 400 to 800 mg/day of MCZ, and various antibiotics (Group I) was evaluated in 7 patients with mycoses (fungemia and fungal infections of the digestive and respiratory systems). The efficacy of the treatment was found to be 3/3. When 200 to 1,200 mg/day of MCZ was combined with various antibiotics (Group III), the therapy was found to be slightly effective (2/4). The rate of fungal eradication was 3/5. 2. The efficacy of combined administration of 400 to 800 mg/day of MCZ, 100 to 250 micrograms/day of G-CSF, and various antibiotics (Group II) in patients with fever of unknown etiology (n = 8) was 4/4. The efficacy of combined administration of 400 to 800 mg/day of MCZ and various antibiotics (Group III) was 3/4. 3. Leukocyte counts were recorded in the 7 patients who had received G-CSF (Groups I and II). The counts rose from < 1,000/microliters before the chemotherapy to > 5,000/microliters in 6 patients (6/7) in 5 to 8 days following drug administration. The favorable clinical efficacy was recorded in all who received MCZ and antibiotics. 4. The objective or subjective adverse effects of this therapeutic modality were limited to mild nausea in a single case. No deviations from norm were noted in clinical or other tests.
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PMID:[Clinical evaluation of combined use of miconazole and G-CSF on deep-seated mycoses in patients with gynecological cancers]. 751 53

One hundred patients with advanced carcinoma undergoing highly cytotoxic chemotherapy were enrolled in a prospective randomized trial comparing subcutaneous G-CSF, thymopentin, a combination of the two, and placebo as preventive treatment of febrile leukopenia. Data from this study show that G-CSF was very active in reducing the incidence of chemotherapy-related fever and leukopenia as compared to placebo (22% versus 64%). This difference was statistically highly significant (P < 0.001). Thymopentin was associated with a reduction in febrile episodes as compared to placebo (52% versus 64%), but this difference did not reach statistical significance. Moreover, the addition of thymopentin to G-CSF did not result in a statistically significant improvement of results obtained with G-CSF alone. Similar results were achieved for fungal infections. Tolerance to thymopentin was excellent, while less than 9% of patients on G-CSF treatment complained of mild nausea and generalized bone pain.
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PMID:A prospective randomized trial of thymopentin versus granulocyte--colony stimulating factor with or without thymopentin in the prevention of febrile episodes in cancer patients undergoing highly cytotoxic chemotherapy. 751 41

We conducted a multicenter Phase II study of BMS-181339 in patients with ovarian cancer. The facilities participating were 23 in number. The total number of cases registered for the study were 62; 57 of them entered for evaluation in drug efficacy, and 58 cases were evaluable in drug safety. All the cases were previously treated with chemotherapy including platinum-based drugs. The clinical responses of BMS-181339 were as follows: CR, 1 case; PR, 13 cases; MR, 3 cases; NC, 13 cases and PD, 27 cases. The response rate was 24.6% (95% CI: 14.1-37.8%). Histologically, the drug showed its efficacy on serous adenocarcinoma 28.2% (11/39), mucinous adenocarcinoma 20.0% (1/5) and clear cell adenocarcinoma 20.0% (1/5). In regional evaluation, the drug demonstrated its efficacy not only on endopelvic lesions 19.0% (4/21) and abdominal lesions 14.3% (2/14), but also on remote metastatic lesions such as hepatic metastasis 30.8% (4/13) and lung/pleura 33.3% (2/6). The drug also showed its efficacy on the cases 22.9% (8/35) refractory to the platinum-based drugs. Major adverse reactions were fever 63.8% (37/58), alopecia 59.3% (32/54), peripheral nerve disorders 28.1% (16/57) such as numbness of the extremities, nausea/vomiting 24.1% (14/58), arthralgia 20.7% (12/58) and diarrhea 20.7% (12/58) etc.. Abnormal alterations in laboratory test values were an incidence rates of 100% for both leukopenia and neutropenia. However, these symptoms were clinically manageable by transient withdrawal of medication, dose reduction and administration of antibiotics and G-CSF. In addition, decrease in hemoglobin 93.1% (54/58), decrease in platelet counts 31.0% (18/58), elevation in GOT 27.6% (16/58), in GPT 31.0% (18/58) and in LDH 20.7% (12/58) were seen, but no serious organopathy was observed. Thus, we confirmed that BMS-181339 was a clinically useful chemotherapeutic agent in patients with ovarian cancer.
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PMID:[A phase II study of BMS-181339 in patients with ovarian cancer. BMS-181339 Ovarian Cancer Study Group]. 794 92

The purpose of this work was to determine the maximum tolerated (phase II) dose of melphalan and etoposide that can be given in conjunction with autologous BM re-infusion in patients who have refractory or relapsed solid tumors. Twenty-six patients with refractory or relapsed breast cancer (n = 15), small cell lung cancer (n = 1), ovarian cancer (n = 3), colorectal cancer (n = 3) or malignant melanoma (n = 4) were enrolled and treated in this phase I study. Patients ranged in age from 31 to 60 years (median 44.5 years). Melphalan 180 mg/m2 (60 mg/m2/day for 3 consecutive days i.v. over 30 min) and etoposide 1200-3600 mg/m2 (400-1200 mg/m2/day for 3 consecutive days i.v. over 4 h) were given followed by autologous BM infusion 60-72 h after completion of chemotherapy. Ten patients received GM-CSF or G-CSF therapy after marrow re-infusion. Regimen-related toxicities included fever, pancytopenia, mucositis, nausea, vomiting, diarrhea, esophagitis, hepatic dysfunction and infection. Neutrophils recovered to > 500 x 10(6)/l and platelets recovered to > 20 x 10(9)/l (without transfusions) a median of 17 days and 20.5 days after marrow infusion, respectively. Dose-limiting toxicity occurred at an etoposide dose of 3600 mg/m2, since 4 of 6 patients treated at this dose level experienced grade 4 NCI Common Toxicity Criteria (mucositis (n = 3) and infection (n = 1)). Complete responses were noted in 7 patients (breast cancer (n = 5), colorectal cancer (n = 1) and melanoma (n = 1)); partial responses were observed in 5 patients. Melphalan 180 mg/m2 and etoposide 3000 mg/m2 is a potent high-dose chemotherapy regimen with significant antineoplastic activity, particularly for breast cancer, and has acceptable toxicity when administered in conjunction with autologous BM re-infusion.
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PMID:Phase I trial of high-dose melphalan, high-dose etoposide and autologous bone marrow re-infusion in solid tumors: an Eastern Cooperative Oncology Group (ECOG) study. 799 70

Imipenem/cilastatin sodium (IPM/CS) which is a broad-spectrum agent against both Gram-positive and -negative bacteria was used in combination with fosfomycin (FOM) as a second-line chemotherapy for severe infections associated with hematologic disorders. FOM was partnered with IPM because FOM may enhance the bacteriocidal effects of IPM when given as pretreatment to IPM/CS therapy. Fifty two patients were treated with IPM/CS plus FOM. Of them, 41 were evaluated for effectiveness. Eleven patients were not evaluated: 4 were treated with a combination of other regimens such as cefixime, gamma-globulin, G-CSF and a large dose of methyl prednisolone; 2 were given IPM/CS plus FOM as a first choice; 3 were observed to have gastrointestinal side effects such as nausea which led to the discontinuation of the combination therapy; and 2 were thought to be suffering from not infectious but tumor fever. An excellent response was observed in 15 (36.6%) patients and a good response in 10 (24.4%), for a overall efficacy rate of 61.0%. Efficacies was 71.4% (5/7) in patients with sepsis, and 60.0% (9/15) in patients whose peripheral granulocyte count was below 100/microliters before chemotherapy. The elimination rates of Gram-positive and -negative bacteria were 57.1% (4/7) and 75.0% (6/8), respectively. In particular, 75.0% (3/4) of Pseudomonas aeruginosa identified were eliminated. Two patients who suffered from tumor fever, 2 who did not receive chemotherapy before the combination chemotherapy and 3 who did not receive a full course of the combination chemotherapy because of side effects, were included in the final evaluation of safety. Side effects were observed in 18 of 48 patients (37.5%). In 1 patient, skin eruption occurred 3 days after the initiation of the combination chemotherapy. In 17 patients, gastrointestinal symptoms such as nausea and vomiting were identified after a few days of IPM/CS plus FOM administration. Degree's of the symptoms were mild, however. Therefore, the treatment was not withdrawn. No abnormal laboratory results such as eosinophilia, liver disfunction or renal disfunction were observed. These results show that IPM/CS plus FOM is effective as a second-line combination chemotherapy for the treatment of severe infections in patients with hematologic disorders.
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PMID:[Clinical evaluation of imipenem/cilastatin sodium and fosfomycin as second-line combination chemotherapy in severe infections associated with hematologic disorders]. 833 78

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1

While the use of 5-HT3 receptor antagonists is clearly justified in patients receiving cisplatin, their role with less emetic drugs is still not defined. The aim of our randomized study was to verify the efficacy of the single standard dose of three 5-HT3-receptor-antagonists in moderately emetic chemotherapies. Sixty chemotherapy-naive breast cancer patients of 30 to 71 years in age, P.S. = 0-1, receiving 5-fluorouracil-epirubicin-cyclophosphamide (FEC 75) q 21 days or cyclophosphamide-methotrexate-5-fluorouracil (CMF) or 120 mg/m2 epirubicin or high dose mitomycin-methotrexate-mitoxantrone (MMM) q 14 days (+ G-CSF) or 100 mg/m2 epirubicin (+ G-CSF) were randomized to receive, 15 min before chemotherapy, 8 mg i.v. bolus of ondansetron or 3 mg i.v. granisetron or 5 mg i.v. tropisetron and no further antiemetic therapy in the following days. 180 cycles were evaluable. Complete protection, (the absence of vomiting episodes,) was respectively 75%, 70% and 70% in the acute and 70%, 82%, 72% in the delayed phases, and an absence of nausea was 56%, 37% and 20% in the acute phase and 50%, 35% and 27% in the delayed, respectively. Complete response, (absence of vomiting and absence or mild nausea,) was 74%, 58.6% and 50.8% in the acute and 64%, 63.7%, 47.3% in the delayed phases, respectively. At the statistical analysis no significant differences between the three drugs were found regarding acute vomiting while ondansetron was superior to granisetron and tropisetron in acute (p = 0.018; p < 0.05) and delayed nausea (P = 0.104; p < 0.01). This activity is practically the same as that we reported (Ann Oncol 1994; 6, suppl 8: 204) with a loading dose on day 1 and maintenance for the following 2-5 days, but with a significantly favorable cost-benefit ratio.
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PMID:Prevention of delayed emesis by a single intravenous bolus dose of 5-HT3-receptor-antagonist in moderately emetogenic chemotherapy. 880 24

The purpose of this study was to evaluate the safety and feasibility of front-line high-dose sequential (HDS) chemotherapy with peripheral blood stem cell (PBSC) transplantation in patients with newly diagnosed high-risk non-Hodgkin's lymphoma (NHL). Thirty-two patients with high-risk NHL (defined by the age-adjusted international index) underwent HDS chemotherapy followed by PBSC transplantation and consolidative radiotherapy. Twenty-eight patients (88%) had intermediate/high grade NHL and four patients (12%) had small noncleaved or lymphoblastic lymphoma. Twenty-four patients were classified as high-intermediate-risk (two risk factors) and eight patients were classified as high-risk (three risk factors). The five phases of HDS (see Fig. 1) consisted of Phase I (adriamycin, vincristine, and prednisone); Phase II (cyclophosphamide, filgrastim [G-CSF], and PBSC harvest); Phase III (methotrexate, leucovorin, vincristine; Phase IV (etoposide, filgrastim [G-CSF]); and Phase V (mitoxantrone, melphalan, autologous peripheral blood stem cell infusion, and filgrastim [G-CSF]). Radiation therapy was given to sites of previous bulk disease, 2400 cGy, (D + 30-100)]. Toxicity, engraftment, hospital utilization, overall survival, and relapse-free survival were evaluated. The high-dose sequential chemotherapeutic regimen was well tolerated. Treatment-related mortality was 6.25% with two deaths occurring secondary to sepsis and one death was caused by progressive disease. The major toxicity in Phase I-IV was grade 3 nausea/vomiting. The major toxicity in Phase V was grade 3 or 4 nausea/vomiting and mucositis. The median follow-up is 18.8 months (range 4-44 months). The overall survival (OS) and relapse-free survival (RFS) at 18 months for all patients were 78% (95% CI 37-90%) and 67% (95% CI 46-88%), respectively. The OS at 18 months for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 82% (95% CI 65-98%) vs. 30% (95% CI 0-86%) (p = 0.0059). One patient in this latter group remains alive at 6 months follow-up. The RFS for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 78% (95% CI 58-97%) vs. 0% (95% CI 0-0%) (p = 0.0004). High-dose sequential chemotherapy with initial PBSC transplantation is well tolerated and appears effective in high-risk NHL. Superior results were noted in patients with intermediate grade versus those with small noncleaved or lymphoblastic NHL.
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PMID:A phase II multicenter trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin's lymphoma. 936 Jul 83

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.
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PMID:A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group. 939 Feb 10

Deferiprone, also known as L1, is an orally active iron chelator that has been studied extensively in clinical trials. The sporadic occurrence of agranulocytosis in association with deferiprone and the highly variable frequency of other possible side effects such as arthralgia have created uncertainty about the true incidence of deferiprone-related complications. A multi-center, 1-year trial was initiated to determine the safety profile of deferiprone. Using the Apotex formulation of deferiprone, 187 patients with thalassemia who were unable or unwilling to use deferoxamine were enrolled in four centers; 162 patients completed one year of therapy. Agranulocytosis (ANC < 500/mm3) occurred in one patient after 15 weeks of treatment, was not accompanied by infection and resolved following treatment with G-CSF. Nine other subjects developed less severe neutropenia (ANC 500-1500/mm3) with the lowest absolute neutrophil count reaching 500-1250/mm3. The neutropenia in these patients developed after 1-50 weeks of therapy, frequently accompanied febrile illnesses, and occurred predominantly in non-splenectomized patients. Reasons other than neutropenia for discontinuing use of deferiprone included nausea (4), voluntary withdrawal (3), high ALT (2), platelet count < 100,000/mm3 (2), low but unconfirmed ANC (1), protocol violation (1) fatigue (1), and depression (1). Mean ALT levels rose within three months of therapy and stabilized thereafter. Arthralgia and nausea and/or vomiting occurred in 6% and 24% of subjects, respectively. In this multi-center trial with weekly monitoring of blood counts, the incidence of agranulocytosis was 0.58 per 100 patient-years, and the frequency of agranulocytosis after one year was 0.5%. These findings support the safety of this formulation of deferiprone, using the careful monitoring system employed in this trial.
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PMID:A multi-center safety trial of the oral iron chelator deferiprone. 966 43


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