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)

In an attempt to develop more effective chemotherapy regimens in advanced nonsmall cell lung cancer (NSCLC), we evaluated docetaxel-ifosfamide-cisplatin (DIP) based on our previous experience with paclitaxel-ifosfamide-cisplatin. Patients with advanced NSCLC (stages III-IV), WHO-PS< or =2, no prior chemotherapy and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered in successive dose levels (DLs) and included docetaxel (80-100 mg/m2 day 1), ifosfamide (4-5 g/m2) and cisplatin (80-100 mg/m2), both divided over days 1 and 2 every 21 days. G-CSF (lenograstin) was administered from days 4-13. Fifty-five patients were accrued (phase I: 15; phase II: 40) and all are evaluable for response and toxicity: median age = 58 (40-72); PS = 1 (0-2); gender = 48 males, 7 females; stages IIIA = 8, IIIB = 19, IV = 28; and histologies were adenocarcinoma (29), squamous (20), large cell (6). Metastatic sites at diagnosis included lymph nodes (33), bone (8), liver (6), brain (6), lung nodules (9), adrenals (7) and soft tissue (1). The dose-limiting toxicity (DLT) was reached at DL4 (Docetaxel: 100 mg/m2-Ifosfamide: 5 g/m2-Cisplatin: 100 mg/m2) consisting of 2 cases of febrile neutropenia (FN), and DL3 (Docetaxel: 100 mg/m2-Ifosfamide: 5 g/m2-Cisplatin: 80 mg/m2) was considered as the maximum tolerated dose (MTD) and recommended for further phase II testing. Among evaluable patients in phase II, 31/46 (67%; CI = 54-81%) responded; 4 were complete responses, 27 partial responses, 12 with stable disease and 3 with progressive disease. The median response duration was 7 months (2-21+), median time to progression (TTP) 8 months (1-23+) and median overall survival (OS) 13 months (2-23+). The 1-year survival was 57%. Grade (Gr) 3/4 toxicities included neutropenia 39/46 with 27 developing Gr4 (< or =7 days) and 20% FN managed successfully with broad-spectrum antibiotics, thrombocytopenia Gr3 3/46-Gr4 1/46, no Gr3 neuropathy, Gr1-2 CNS toxicity in 12, no renal toxicity, 15 Gr2 myalgias, 17 Gr2 diarrhea and 10 Gr3 vomiting. In the present phase I-II study, DIP appears highly active and tolerable in advanced NSCLC in the outpatient setting. Randomized comparisons to current standard 2-drug regimens will be warranted.
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PMID:A phase I-II study of docetaxel-ifosfamide-cisplatin (DIP) combination chemotherapy regimen in advanced nonsmall cell lung cancer. 1185 98

Before and after launch of 5-HT3, antagonist, necessary dose and duration of chemotherapy were compared between the patients who were confirmed to have undergone chemotherapy before the launch of 5-HT3 antagonist (retrospective group) and the ones currently using ondansetron (OND) for chemotherapy-induced emesis (prospective group). Clinical usefulness of OND was evaluated through survey on quality of life (QOL) to patients and questionnaires to physicians, nurses & patients. Necessary dose of chemotherapy was evaluated by investigating actual dose of cisplatin (CDDP). As the result, necessary dose of CDDP was confirmed to be different between retrospective and prospective groups. The influence on the actual CDDP dose was observed with or without use of G-CSF or by recommended dose of CDDP, while no influence by 5-HT3 antagonist was observed. For necessary duration of chemotherapy, significant difference was not observed between retrospective or prospective groups. On the other hand, actual CDDP dose or necessary duration of chemotherapy were confirmed to be greatly affected by chemotherapy-induced adverse events such as blood disorder (e.g. bone marrow suppression) or renal disorder, rather than chemotherapy-induced emesis. As the result of QOL survey to patients and other questionnaires to medical staff & patients, the fact of chemotherapy-induced emesis to lower the patient's QOL as well as the importance of emetic control was confirmed. It was also confirmed that the workload of nurses or other medical staff has lessened since the launch of 5-HT3 antagonists.
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PMID:[Clinical usefulness of ondansetron injection in patients receiving cancer chemotherapy]. 1186 33

A phase II trial was performed to determine the antitumour efficacy and tolerance of combined paclitaxel and cisplatin with or without hematopoetic growth factor support in patients with advanced gastric cancer. Forty-five patients with histologically confirmed metastatic gastric cancer were entered in this trial. Treatment consisted of 2-weekly courses of paclitaxel 160 mg per m2 and cisplatin 60 mg per m2 both given on day 1. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1000-2000 per microl), a 5-day course of human granulocyte colony-stimulating factor 5 microg x kg(-1) per day was given subcutaneously; in addition, if haemoglobin was <12.0 mg dl(-1), erythropoietin 10 000 IU was administered subcutaneously three times per week. The confirmed overall response rate (intent-to-treat) was 44%, including five complete (11%) and 15 partial remissions (33%). Twelve patients had stable disease (27%), 11 (24%) progressed while on chemotherapy, and two patients were not evaluable. The median time to response was 3 months, the median time to progression 7.0 months, and the median survival time was 11.2 months with 12 patients currently alive. Haematologic toxicity was common, though WHO grade 4 neutropenia occurred in only five patients (11%). Apart from total alopecia in 16 patients (36%), severe non-haematologic adverse reactions included grade 3 peripheral neuropathy in six (13%) and anaphylaxis in two patients. In addition, there was one patient each who experienced grade 3 emesis, diarrhea, and infection, respectively. Our data suggest that the combination of paclitaxel and cisplatin with or without G-CSF and/or erythropoietin has promising therapeutic activity in patients with advanced gastric cancer.
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PMID:Effective combination chemotherapy with paclitaxel and cisplatin with or without human granulocyte colony-stimulating factor and/or erythropoietin in patients with advanced gastric cancer. 1208 76

We conducted a study of docetaxel-carboplatin combination therapy to confirm the efficacy and toxicity in chemotherapy-naive patients with ovarian cancer. Docetaxel 70 mg/m2 and carboplatin (area under the concentration-vs.-time curve of 5) were administered consecutively on day 1 of a 21-day cycle for five planned cycles in chemo-naive patients with the International Federation of Gynecology and Obstetrics stage IC to IV ovarian cancer with or without successful cytoreductive surgery at staging laparotomy. Twenty-six patients (median age, 53 years; range, 34-76 years) were enrolled into this trial at Niigata University Hospital. The major toxicity with this regimen was neutropenia. The incidence of grade 3 and 4 neutropenia were 27% (7/26) and 69% (18/26), respectively. However, the neutropenia was brief and reversible with G-CSF support. Nausea/emesis, fatigue, arthralgia/myalgias, and alopecia were the most common nonhematologic toxicities, in which no grade 3 or 4 toxicity was observed. Neurotoxicity was infrequently observed. Nine of 11 assessable patients responded to the regimen. We conclude that the combination of carboplatin and docetaxel seems to be highly active in ovarian cancer with the major toxicity of neutropenia, and the extremely low incidence of clinically significant neurotoxicity. Randomized controlled clinical trials should be conducted to define a role for this regimen in ovarian cancer.
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PMID:Docetaxel in combination with carboplatin for chemo-naive patients with epithelial ovarian cancer. 1244 46

Since the terrorist attack of September 11, 2001, preparation by the health care system for an act of terrorism has been mandated by leaders of governments. Scenarios for terrorist acts involving radioactive material have been identified, and approaches to management (based on past experience from atomic weapons detonations and radiation accidents) have been developed. Because of their experience in managing patients with profound cytopenia and/or marrow aplasia, hematologists will be asked to play a significant role in evaluating and treating victims of mass accidental or deliberate exposure to radiation. This review provides a framework for understanding how radiation levels are quantified, how radiation alters the function of hematopoietic (and nonhematopoietic) cells and tissues, and how victims receiving a significant radiation dose can be identified and managed. In Section I, Dr. Nicholas Dainiak reviews four components of the Acute Radiation Syndrome: the hematopoietic, neurovascular, gastrointestinal and cutaneous subsyndromes. Clinical signs and symptoms are discussed for exposed individuals at the time of initial presentation (the prodromal phase) and during their course of disease (the manifest illness). In Section II, he presents clinical and laboratory methods to assess radiation doses, including time to onset and severity of vomiting, rate of decline in absolute blood lymphocyte count and the appearance of chromosome aberrations such as dicentrics and ring forms. Potential scenarios of a radiation terrorist event are reviewed, and methods for initial clinical assessment, triage, and early management of the acute radiation syndrome and its component subsyndromes are summarized. In Section III, Dr. Jamie Waselenko reviews the hematopoietic syndrome, and presents guidelines for the use of cytokine therapy, antibiotics, and supportive care that have been developed by the Strategic National Pharmaceutical Stockpile Working Group. Results of preclinical and clinical growth factor therapy studies with G-CSF, GM-CSF, pegylated G-CSF, SCF, and IL-3 are summarized. When and how potassium iodide should be used after exposure to radioiodines is also reviewed. In Section IV, Dr. James Armitage describes a narrow "window" of 7 to 10 Gy where therapy with stem cell transplantation may be appropriate. Victims who are candidates for allotransplantation should not have major trauma or significant injury to other (nonhematopoietic) tissues. Rarely, victims may have an identical sibling or autologous stored marrow or blood stem cells, in which case the threshold for transplantation is 4 Gy. In Section V, Dr. Thomas MacVittie describes new directions for therapy, using cytokines such as IL-7, keratinocyte growth factor, and FLT-3. The potential for combinations of cytokines to enhance hematopoietic recovery is also reviewed.
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PMID:The hematologist and radiation casualties. 1463 95

We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/microL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.
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PMID:IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. 1698 32

Currently, randomized phase III trials have demonstrated that docetaxel is an effective strategy in the adjuvant treatment of breast cancer. However, previous attempts to incorporate docetaxel with an anthracycline in a dose-dense regimen have been unsuccessful. Therefore, new schedules containing both drugs should be explored. Forty-four patients with high-risk operable breast cancer entered this feasibility study. They were treated with three cycles of epirubicin 110 mg/m2 every 2 wk with G-CSF followed by three cycles of "intensified" CMF (840 mg/m2 cyclophosphamide; 57 mg/m2 methotrexate; 840 mg/m2 fluorouracil) every 2 wk with G-CSF followed 3 wk later by nine weekly cycles of 35 mg/m2 docetaxel (E-CMF-doc). Totally, 39 patients (89%) received all cycles of chemotherapy. The vast majority (92%) of cycles were administered at full dose. Therefore, dose intensity was sufficiently maintained for all drugs. Toxicity was generally mild to moderate. Most frequently recorded side effects apart from alopecia were neutropenia (54%) and nausea/vomiting (89%). Infection developed in nine patients. Two cases of febrile neutropenia were reported. The E-CMF-doc regimen, as used in this study, is feasible and well tolerated. Its impact on survival should be evaluated in phase III trials.
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PMID:Adjuvant dose-dense sequential chemotherapy with epirubicin, CMF, and weekly docetaxel is feasible and safe in patients with operable breast cancer. 1730 6

Purpose. To define the maximally tolerated dose (MTD) of ifosfamide when given with G-CSF on an every other week schedule, and to define the MTD of edatrexate that can be given every two weeks with an intense schedule of ifosfamide.Patients and Methods. Forty-one patients with metastatic or unresectable, locally advanced sarcoma participated in this 2-step phase I trial.The starting dose of ifosfamide was 10 gm/m(2) given by continuous intravenous infusion over 4 days every 2 weeks.When the MTD was defined, edatrexate, beginning at a dose of 40 mg/m(2) intravenously every 2 weeks was added in subsequent cohorts of patients.Results. Myelosuppression was the most prominent toxicity. Fatigue, nausea, and vomiting were observed in the majority of patients. Ifosfamide 12 gm/m(2) given every 2 weeks approached or exceeded the MTD. Edatrexate 100 mg/m(2) could be given safety as an intravenous bolus with ifosfamide 10 gm/m(2) every 2 weeks. Therapeutic responses were observed in patients with measurable disease.Conclusions. This study demonstrates the feasibility of administering a dose-intense schedule of ifosfamide alone or ifosfamide with edatrexate that might be applied in the adjuvant or neo-adjuvant setting.
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PMID:Evaluation of dose-intense Ifosfamide, with and without edatrexate, in adults with sarcoma. 1852 Dec 74

Receptor activated tyrosine kinases such as c-kit, c-fms and PDGFR are known targets of inhibition by imatinib mesylate (Gleevec) and are expressed on AML blasts. Marrow stromal cells and monocytes express KIT ligand, M-CSF and PDGF and are therefore capable of activating survival pathways in these leukemic cells. Given the synergy in vitro between Ara-C and imatinib mesylate on AML cell growth inhibition, we initiated a Phase I study combining CLAG+imatinib mesylate in AML patients. Patients with relapsed, refractory AML or CML myeloid blast crisis were eligible to receive Cladribine 5mg/m(2) days 3-7, Cytarabine 2gm/m(2) days 3-7, G-CSF 300mcg days 2-7, and escalating doses of imatinib mesylate given on days 1-15. The level 1 Gleevec dose was 400mg, while level 2 was 600mg and the level 3 dose 800mg. A total of 16 patients were enrolled, 15 AML and 1 CML myeloid blast crisis. The dose escalation occurred as planned and there was no clear evidence of added toxicity due to imatinib mesylate. One patient with an extensive cardiac history died of cardiac causes on day 1 of therapy however no other deaths occurred within 30 days of starting therapy. One patient had a Grade 3 skin rash at dose level 2. The most common toxicities encountered during induction therapy were nausea, vomiting, rash and diarrhea that were transient and/or reversible. At the 800mg dose 1 patient developed a decline in cardiac ejection fraction on day 20 who later died of sepsis, so this was considered a dose limiting toxicity. Of 16 evaluable patients 11 achieved a hypocellular marrow after initial induction with 1 additional patient achieving a hypocellular marrow following a second course of the same regimen. Four patients (25%) achieved a complete morphologic response with normal cytogenetics, 2 patients (12.5%) achieved a complete morphologic response only and 1 patient had a complete response in the bone marrow but incomplete blood count recovery. The overall response rate was 43.8%. The median overall survival was 175 days (95% CI 16.24-333.76) and the median relapse free survival was 76 days. The addition of imatinib mesylate to CLAG was well tolerated with acceptable toxicities and response rates comparable to other salvage regimens. To assess the efficacy of imatinib mesylate in combination with CLAG, a larger phase II trial is now planned.
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PMID:Phase I study of cladribine, cytarabine (Ara-C), granulocyte colony stimulating factor (G-CSF) (CLAG Regimen) and simultaneous escalating doses of imatinib mesylate (Gleevec) in relapsed/refractory AML. 1857 21

A Phase I / II study of docetaxel (DOC) and cisplatin (CDDP) combination therapy was conducted. The respective recommended dose (RD) in a phase I study was DOC 60 mg/m(2) and CDDP 80 mg/m(2). We performed a multicenter phase II study to assess the antitumor activity and toxicity of this RD. Patients with recurrent or unresectable squamous cell carcinoma of the head and neck were eligible. For inclusion in this study, patients were required to be >or=20<70 years of age with a Performance Status of 0 to 2. Adequate bone marrow as well as adequate renal and liver function were required. We assessed 22 patients, 13 of whom were enrolled in the phase II study, and 9 patients in phase I were given the RD. Grade 3 or higher neutropenia occurred in 12 patients (55%). There was no episode of febrile neutropenia of more than 3 days or grade 4 neutropenia of more than 3 days receiving G-CSF. Nausea was the most frequent toxicity, but only one patient experienced vomiting of more than grade 3. Pneumonia (grade 3), thrombocytopenia (grade 4) and emphysema (grade 2) were observed. No one achieved a complete response (CR) and 5 achieved a partial response (PR), for an overall response rate of 22.7% (5/22). Stable disease (SD) was seen in 11 and progressive disease (PD) in 6. In 21 of 22 patients, a relapse occurred despite previous treatment. For this population, the response rate was 19.0% (4/21).
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PMID:[A Phase II study of docetaxel and cisplatin in patients with recurrent or unresectable squamous cell carcinoma of the head and neck]. 1969 66


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