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 6 dogs with multicentric lymphosarcoma, salmonellosis developed shortly after the start of anticancer chemotherapy. Three of the dogs died. Signs of illness in those that died were vomiting, diarrhea, neutropenia, anorexia, and fever, usually within 3 days of the start of chemotherapy.
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PMID:Salmonellosis in dogs with lymphosarcoma. 689 47

A phase II study of mitoxantrone, an anthraquinone derivative with structural similarities to adriamycin, has been carried out in 34 patients with advanced breast carcinoma and other malignancies. The first 20 patients were treated with a starting dose of 12 mg/m2 by IV infusion repeated every 3 weeks; this was escalated to 14 mg/m2 in the subsequent 14 patients. Of the 29 patients with advanced breast carcinoma, 8 achieved a partial response and two further patients achieved a mixed response. There were no complete responses. Of the eight responding patients, five had received no prior chemotherapy. Response duration ranged from 3 1/2 months to 10+ months. No responses were seen in the other five patients, three whom had small cell carcinoma of the lung, and one colonic carcinoma. Neutropenia was the most frequently seen toxicity but was usually mild and transient; WBC fell to less than 2,000/mm3 in eight patients and to less than 1,000/mm3 in only two. Otherwise, the drug was well tolerated; nausea occurred in 35% of patients and vomiting in 21%; severe alopecia requiring a wig was never seen. Mitoxantrone appears to be a well-tolerated and clinically active agent against advanced breast carcinoma.
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PMID:Mitoxantrone: a phase II study in the treatment of patients with advanced breast carcinoma and other solid tumours. 710 82

Topoisomerase I inhibitors are a new therapeutic class whose clinical evaluation began a few years ago; Irinotecan (CPT-11) gave interesting results in colon cancer; side effects were neutropenia, diarrhea, vomiting and a cholinergic syndrome. Topotecan was useful in lung and ovarian cancer; side effects were mostly hematologic. Undergoing studies concern dose optimization, mode of administration and therapeutic associations.
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PMID:[Topoisomerase I inhibitors. Review of phase II trials with irinotecan (CPT-11) and topotecan]. 749 18

Intraperitoneal (IP) administration of fluorinated pyrimidines has been evaluated for ovarian and gastrointestinal malignancies in phase I, II, and III trials. The tolerance and pharmacokinetic profile of IP 5-fluoro-2'-deoxyuridine(FUDR) alone and with (R,S)-leucovorin ((R,S)-LV) have each been evaluated in previous phase I studies. FUDR doses of 3 g per day with and without (R,S)-LV doses up to 640 mg per day given IP are well tolerated. The current phase I study was designed to determine the pharmacokinetic profiles and clinical tolerance of escalating doses of the pure biologically active S-isomer of leucovorin ((S)-LV) given IP with the same dosing schedule of FUDR. A group of 16 patients with disease confined to the abdominal cavity were treated in this study. Pharmacokinetic studies of blood and peritoneal fluid, toxicity profiles, and clinical response for the first three cycles are reported here. The toxicity profile did not significantly differ from the prior two studies. All non-hematologic toxicities, such as fatigue, nausea, vomiting, diarrhea, and abdominal discomfort were less than grade 4, and most were less than grade 3. Neutropenia and thrombocytopenia were uncommon and observed only in patients with compromised bone marrow reserve. The pharmacokinetic profiles were also congruent with the previous studies and indicate a three-log advantage for FUDR. The (S)-LV profiles in the peritoneal cavity paralleled those of FUDR. Antitumor effects or absence of progression until after cessation of therapy were documented in 11 patients. At a median follow-up of 18 months 44% of patients were alive. IP administration of 3-g of FUDR and up to 640 mg (S)-LV daily for three days was well tolerated. The tolerance and antitumor effects observed during IP FUDR and LV in these studies encourage further exploration of this regimen against ovarian and gastrointestinal malignancies. The actual role and optimal dose of LV as an enhancer of the antitumor actions of FUDR administered by this route remain unknown.
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PMID:Intraperitoneal 5-fluoro-2'-deoxyuridine (FUDR) and (S)-leucovorin for disease predominantly confined to the peritoneal cavity: a pharmacokinetic and toxicity study. 749 94

A total of 18 patients received 6-week ambulatory infusions of carboplatin in groups at dose levels of 14, 28, 35 and 42 mg/m2 per day. The dose-limiting toxicity was myelosuppression. At 42 mg/m2, three of four patients had WHO grade 4 and one of four had grade 3 neutropenia, whereas two patients had grade 3 thrombocytopenia. At 35 mg/m2, two of five patients had grade 3 neutropenia, whereas one had grade 4 and two had grade 3 thrombocytopenia. Non-hematological toxicities were predominantly gastrointestinal, with 3 of 18 patients experiencing grade 3 emesis. Total and ultrafiltrable platinum (UFPt) were assayed by flameless atomic absorption spectrometry in weekly and post-infusion plasma and urine samples. In plasma, levels of total platinum increased throughout the infusion, and the protein binding slowly increased from 60% platinum bound at week 1 to 90% bound by week 4. Although the UFPt level reached a steady state within 1 week, the concentration did not increase with the dose level, remaining at a mean value of 0.58 +/- 0.24 microM. Renal excretion of platinum accounted for 70 +/- 12% of the dose at steady state. There was a high inter-patient variability in both total body clearance of UFPt (range, 83-603 ml/min) and renal clearance (range, 67-390 ml/min). A terminal elimination half-life of 13-27 h was noted for post-infusion UFPt. Neutropenia was linearly related to the total daily carboplatin dose, but neither neutropenia nor thrombocytopenia could be related to steady-state UFPt or the UFPt area under the concentration-time curve (AUC). The recommended dose for phase II studies is 28 mg/m2 per day.
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PMID:A phase I and pharmacokinetics study of prolonged ambulatory-infusion carboplatin. 749 1

The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily x5 schedule has been developed further with dose escalation using granulocyte-colony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous intravenous infusion to patients with refractory leukemia has had promising antileukemic responses. A separate series of in vitro studies indicates that a modest degree of resistance to the cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has defined an MTD of 240 mg/m2, with dose escalation being limited by several toxicities. These included an acute treatment-related syndrome of flushing, warmth, nausea, vomiting, and diarrhea; a subacute combination of nausea, diarrhea, anorexia, and weight loss; and/or neutropenia. Antitumor activity has been observed with topotecan and irinotecan in patients with a variety of solid tumors and refractory leukemia in our studies, which supports the widespread enthusiasm for this group of compounds.
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PMID:Camptothecin analogues: studies from the Johns Hopkins Oncology Center. 752 Aug 44

Several clinical trials have demonstrated that cisplatin-based chemotherapy for primary intracranial germ-cell tumors is effective as a neoadjuvant chemotherapy. In this report, we describe a 6-year-old boy, Down syndrome and Hirschsprung's disease with intracranial pure yolk sac tumor treated by combined chemotherapy with cisplatin, vinblastine, bleomycin and cyclophosphamide (modified VAB-6 regimen). He had been admitted to our hospital because of intractable vomiting, and left facial nerve palsy since 1 month before. An MRI revealed an enlarged mass, 4cm in diameter, in the left cerebello-pontine angle with uniformal enhancement by Gd-DTPA, and bilateral ventricular dilatation. He was found to have increased serum alpha-fetoprotein level (AFP 11, 786ng/ml), but not human chorionic gonadotropin beta-subunit. After a partial resection of the tumor, diagnosed as pure yolk sac tumor, and ventriculo-peritoneal shunt, three courses of combined chemotherapy with cisplatin, bleomycin, vinblastine and cyclophosphamide (modified VAB-6 therapy) were carried out. The serum AFP level returned to normal, and the tumor mass entirely disappeared (a complete response) on MRI after the second course of chemotherapy. However, cisplatin-induced vomiting and mild neutropenia and renal tubular injury developed after the third course of chemotherapy. Irrespective of administration of recombinant human G-CSF and broad spectrum antibiotics, he suffered from pneumonia and died of septic shock and multiple organ failure. Autopsy showed microscopic residual tumors. The combination chemotherapy with cisplatin, bleomycin, vinblastine and cyclophosphamide is effective for initial treatment of childhood intracranial yolk sac tumor. It is necessary, however, to reevaluate the cisplatin dosage and treatment schedule in order to reduce such side effects as bone marrow suppression and renal damage.
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PMID:[A case report of a 6-year-old boy with intracranial yolk sac tumor treated by VAB-6 regimen]. 753 Dec 96

A dose-finding study was set up to identify the optimal dose of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin for phase II studies in patients with advanced chemotherapy-naive non-small cell lung cancer (NSCLC). The influence of drug sequence on the toxicity and pharmacokinetics of both agents was also assessed. To develop an ambulatory regimen for palliation of advanced NSCLC, paclitaxel was infused over 3 hours with standard premedication and carboplatin over 30 minutes. Cycles were repeated every 4 weeks. At each dose level, at least six patients were randomized to receive either paclitaxel followed by carboplatin or the reverse sequence. In the second and following cycles the alternate sequence was administered. The pharmacokinetics of both paclitaxel and carboplatin were compared in the first two cycles in at least two patients per dose level. Sixty-two patients have been entered in this study. Paclitaxel was increased from 100 mg/m2 in 25 mg/m2 increments up to a maximum of 225 mg/m2 combined with a fixed carboplatin dose (300 mg/m2). Thereafter, the drug doses were increased to a maximum of 400 mg/m2 carboplatin and 250 mg/m2 paclitaxel. In 243 cycles, the most frequent side effects were neutropenia, alopecia, and mild emesis. Only one patient developed a major hypersensitivity reaction to paclitaxel. Bone pain, myalgia, and peripheral neurotoxicity occurred more frequently at paclitaxel doses above 200 mg/m2. No significant differences in toxicity or in the pharmacokinetics of either drug were observed between the two drug sequences. The pharmacokinetics of paclitaxel were nonlinear and consistent with saturation. At the highest paclitaxel dose (250 mg/m2 with carboplatin 350 mg/m2) a toxic death due to severe leukopenia, thrombocytopenia, and hemorrhage occurred. Safe doses for phase II trials in untreated NSCLC are 200 mg/m2 paclitaxel with 300 mg/m2 carboplatin. Of 50 evaluable patients, five of the six major responses were observed at paclitaxel doses of 175 mg/m2 and above, which suggests a dose-response relationship for paclitaxel in NSCLC.
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PMID:Dose-finding and sequencing study of paclitaxel and carboplatin in non-small cell lung cancer. 754 30

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer. 755 41

Dengue fever is a viral disease, transmitted to man via mosquito bites. It is endemic in tropical regions (10 million infected annually) and is characterized by high fever, headache, myalgia, lethargy, vomiting, rash and neutropenia. The upward trend in the number of young Israelis visiting tropical countries increases the number of those potentially exposed to this disease. We present 4 Israelis who returned with dengue fever from Thailand.
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PMID:[Dengue fever]. 755 5


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