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)

We report on an 66-year old female in whom we diagnosed uterine carcinosarcoma and concurrent breast cancer. As first-line treatment the patient received ifosfamide 4.8 mg/m2 body surface. During her second course of chemotherapy she developed sequentially life-threatening toxicities; severe emesis followed by nephrotoxicity, neurotoxicity and myelosuppression. Early prophylactic administration of rhG-CSF (Filgrastim) helped to overcome severe, potentially fatal myelosuppression. The course of severe toxicities following high doses of ifosfamide might reflect a dependent sequence, where one organ failure causes a subsequent organ failure. Prophylactic treatment of anticipated toxicity should be considered for the management of severe ifosfamide-induced toxicity. Such treatment may consist of sufficient antiemesis, sufficient hydration, as well as a therapy with methylene blue in case of severe neurotoxicity.
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PMID:[Sequential course and prospective management of ifosfamide-induced multi-organ toxicity]. 903 65

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels </=150 mg/m2; all patients had pretreatment endomyocardial biopsy scores less than 1. One patient treated at the highest dose level of doxorubicin (175 mg/m2) developed symptoms of mild congestive heart failure following two cycles of chemotherapy. Pre- and posttreatment radionuclide ejection fractions were 65 and 45%, respectively; this patient had a posttreatment endomyocardial biopsy score of 1 (damage to <5% of myocytes). One additional patient at this dose level had an asymptomatic biopsy score of 1, with a decrease in ejection fraction from 62 to 43%; this recovered to 58% 5 months after completion of chemotherapy. Six additional patients treated at lower dose levels had abnormal posttreatment endomyocardial biopsies without abnormal posttreatment ejection fractions. Nine patients received only one cycle of chemotherapy: five patients due to decreased cardiac ejection fraction following cycle 1 (two of these patients had normal endomyocardial biopsies, and two patients had biopsy scores of 1); one patient secondary to tumor progression following cycle one; one patient due to persistently detectable Clostridium difficile toxin in the stool; one patient refused cycle two; and one patient died following cycle one of complications related to sepsis. A single patient experienced a grand mal seizure associated with orthostatic hypotension, which was considered the dose-limiting toxicity. The median duration (over two cycles) of granulocytopenia (absolute granulocyte count <500/microliter) at the maximally tolerated dose level of 150 mg/m2 was 8.5 days (range, 5-13 days), and the median duration of thrombocytopenia (platelets <20,000/microliter) was 2.5 days (range, 0-9 days). The median duration of hospitalization including chemotherapy administration was 23 days (range, 19-36 days). Other toxicities included stomatitis, fever, diarrhea, and emesis. One patient developed acute leukemia 54 months posttreatment. We conclude that two courses of high-dose cyclophosphamide and doxorubicin using granulocyte colony-stimulating factor are feasible and safe with tolerable myocardial toxicity as evidenced by serial endomyocardial biopsies. The dose-limiting toxicity encountered was a grand mal seizure. The recommended Phase II dose is doxorubicin 150 mg/m2 administered as a 96-h infusion on days 1-4, with cyclophosphamide 4. 2 g/m2 on day 5 and G-CSF 5 microgram/kg/day started on day 6 and administered until the total WBC is above 10,000/microliter for three consecutive days.
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PMID:High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support. 981 32

Phase II studies have suggested an improved response rate and acceptable toxicity profile associated with gemcitabine combinations compared to gemcitabine alone for treatment of metastatic adenocarcinoma of the pancreas. The GFP regimen (gemcitabine, 5-fluorouracil, leucovorin, and cisplatin) is based on laboratory evidence of disease-specific chemotherapy interaction. This retrospective analysis examined the outcome of 49 consecutive patients with histologically confirmed metastatic pancreatic adenocarcinoma treated between July 1998 and September 2000. Day 1 treatment consisted of gemcitabine 500 mg/m2 over 30 minutes and then leucovorin 300 mg bolus, 5-fluorouracil (5-FU) 400 mg/m2 bolus, followed by infusional 5-FU 600 mg/m2 over 8 hours. Day 2 consisted of leucovorin 300 mg bolus, 5-FU 400 mg/m2 bolus, followed by cisplatin 50-75 mg/m2 over 30 minutes and then infusional 5-FU 600 mg/m2 over 8 hours. Treatment was administered every 2 weeks. Median patient age was 61.5 years, 74% were men, and 20 patients had refractory disease (11 patients had disease progression upon gemcitabine-based therapy). Grade 3-4 toxic effects (% patients) consisted of neutropenia (30%), thrombocytopenia (14%), anemia (8%), and neutropenic fever (2%). Grade 3-4 nonhematological toxicities (% patients) consisted of neuropathy (14%), ototoxicity (8%), nephrotoxicity (6%), nausea/vomiting (14%), and mucositis (10%). The majority of dose reductions were made for neuropathy or cytopenias. Filgrastim and erythropoietin were given as needed to promote dose intensity. Eight patients attained a partial response (PR) by RECIST criteria. Fourteen had stable disease (SD). Two patients attaining PR and two attaining SD had progressive disease with prior gemcitabine-based therapy. The median time to disease progression (TTP) from GFP start was 9 weeks. For all 49 patients, the median overall survival (OS) from GFP start was 10.6 months, 12-month survival was 46%, and 24-month survival was 30%. Notably, upon disease progression, 31 patients continued to receive the GFP regimen with irinotecan 80 mg/m2 inserted on day 1 following gemcitabine, the G-FLIP regimen (gemcitabine, 5-fluorouracil, leucovorin, irinotecan, and cisplatin). Measured from G-FLIP initiation, the TTP for the 31 patients treated sequentially was 10 weeks, and for the 14 patients attaining SD or PR the TTP was 25 weeks. The median overall survival measured from GFP initiation was 11.8 months. The response rate, non-cross resistance, TTP, OS, and tolerability warrant prospective development of this novel combination. This experience also demonstrates that adding a single new drug such as irinotecan to the same first-line chemotherapy combination upon disease progression may be an important alternative for the treatment of relapsed/resistant cancer.
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PMID:Biweekly low-dose sequential gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (GFP): a highly active novel therapy for metastatic adenocarcinoma of the exocrine pancreas. 1453 37

Filgrastim, a recombinant G-CSF, is the standard drug used to mobilise haematopoietic stem cells for collection prior to autologous transplantation in patients with lymphoma and myeloma. Plerixafor, a CXCR4 receptor antagonist, is now authorised in the European Union for use in combination with G-CSF when stem cell mobilisation with G-CSF alone is unsuccessful. Clinical evaluation is based on two comparative trials with similar designs. In a trial in 302 myeloma patients, the G-CSF-plerixafor combination was associated with a statistically significantly higher rate of successful mobilisation, defined as collection of at least 6 x 10(6) CD34+ cells after one or two apheresis sessions, than a combination of G-CSF and placebo (71.6% versus 34.4%). The same effect was observed in a trial involving 298 lymphoma patients, in which the CD34+ cell target number was at least 5 x 10(6) after a maximum of 4 apheresis sessions (59% versus 20%). In these trials, the addition of plerixafor to G-CSF increased the frequency of injection site reactions (55% versus 36%) and was associated with twice as many gastrointestinal disorders (diarrhoea and nausea or vomiting). There was no difference between the combined treatments in terms of disease-related mortality at one year (about 8%). However, longer follow-up is needed to ensure that plerixafor does not lead to disease aggravation by mobilising malignant cells. Given the long-term uncertainties, plerixafor should be reserved for patients in whom G-CSF alone fails to yield a sufficient number of stem cells required for transplantation.
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PMID:Plerixafor. Only for certain patients when G-CSF stem cell mobilisation fails. 2093 42

Cisplatin and carboplatin are both active in ovarian cancer with different toxicity profiles; thus, dose intensification may be possible by combining them. The aim of the present study was to determine the maximum tolerated dose of carboplatin combined with fixed doses of cisplatin and cyclophosphamide without and with support of lenograstim. Cisplatin (60 mg/m(2)), cyclophosphamide (600 mg/m(2)) and carboplatin (starting dose 200 mg/m(2)) were given on day 1 every 3 weeks for 4 cycles. Escalated dose levels for carboplatin were planned by increments of 50 mg/m(2) per level. Lenograstim (L) (150 mu g/m(2)/day subcutaneously) was given in case of grade 4 leukopenia (levels without support) or from day 5 up to leukocyte >10,000/mm(3) after nadir (levels with support). Four levels were studied (200, 250, 250 + lenograstim, 300 + lenograstim) with 7, 7, 8, and 7 patients enrolled, respectively. Unacceptable toxicity was induced in 1 patient at the level I (grade 4 thrombocytopenia), in 4 patients at the level 2 (2 prolonged grade 2 leukopenia, 1 grade 4 leukopenia with concomitant grade 4 thrombocytopenia and 1 grade 4 thrombocytopenia), in 1 patient at the level 2 + L (grade 4 thrombocytopenia) and in 3 patients at the level 3 + L (3 grade 4 thrombocytopenia). Thus, 200 mg/m(2) and 250 mg/m(2) were defined as carboplatin MTDs without and with lenograstim support, respectively. Median total platinum (cisplatin + 1/4 carboplatin) delivered dose-intensities were 33, 32, 38 and 44 mg/m(2)/week at the four levels, respectively. Hematological toxicity was overall mild. In no case was febrile neutropenia recorded. Grade 4 thrombocytopenia was always transient and never symptomatic. Grade 3 vomiting was the only severe non-hematological toxicity reported in 5 patients. Out of 16 patients with measurable disease, 11 objective responses were obtained (5 complete and 6 partial) for an overall response rate of 69% (95% exact CL 41-89%). Recommended dose of carboplatin is 200 mg/m(2) without and 250 mg/m(2) with support of lenograstim when combined with cisplatin 60 mg/m(2) and cyclophosphamide 600 mg/m(2). Dose limiting toxicity is persistent leukopenia without and grade 4 thrombocytopenia with support of lenograstim.
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PMID:Phase I study of carboplatin, cisplatin, and cyclophosphamide without and with lenograstim for the treatment of ovarian cancer. 2152 98