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 a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies.
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PMID:Treatment results of the thioether lipid ilmofosine in patients with malignant tumours. 132 33

A 46-year-old woman presented with abdominal pain, nausea vomiting and abdominal distention. Small bowel x-rays and CT scan of the abdomen revealed small bowel obstruction due to malignant melanoma. The diagnosis of cutaneous melanoma was performed 8 years prior to admission on one lesion in the back. Patient received surgical treatment. Completed resection of an involved jejunal [correction of ileal] segment was performed. Three tumor masses were found at laparotomy. Metastasis from malignant melanoma at the gastrointestinal tract occurs frequently though rarely are these intestinal lesions symptomatic. The efficacy of surgical treatment for symptomatic metastatic melanoma is justified to relief symptoms and prolonged survival.
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PMID:[Symptomatic malignant melanoma of the small intestine]. 134 Nov 16

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.
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PMID:Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. 139 37

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-gamma (rIFN-gamma) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-gamma (0.1 or 0.25 mg/m2/day) was administered by intramuscular injection, days 1-7 and rIL-2 (12, 18, or 24 x 10(6) IU/m2/day) was administered by a 15-min intravenous bolus, days 8-12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-gamma, 0.25 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity. It is unlikely that higher doses of either agent would be tolerated, and for further study using this schedule, we recommend the doses: rIFN-gamma, 0.1 mg/m2/day, and rIL-2, 24 x 10(6) IU/m2/day.
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PMID:A Southwest Oncology Group Phase I study of the sequential combination of recombinant interferon-gamma and recombinant interleukin-2 in patients with cancer. 151 22

Spiroplatin was investigated in a multicenter phase II study, during which the drug was given over 4 h. 64 Patients with nine different solid tumors received 141 cycles of spiroplatin at a dose of 30 mg/m2 every 3 weeks. Most important side effects included nausea, vomiting, myelosuppression, and renal toxicity. Four of 11 evaluable patients with prior cisplatin developed increases in serum creatinine (3 transient, 1 died of renal failure). Of 51 patients without prior cisplatin 2 had a transient increase in serum creatinine levels, and 2 showed persistent changes, in 1 of them leading to hemodialysis. Pre- and posthydration did not reduce drug-induced nephrotoxicity. Only 3 patients showed a response; 1 with renal cell carcinoma, 1 with ovarian carcinoma, and 1 with malignant melanoma. Based on the absence of striking antitumor activity and on the presence of severe unpredictable renal toxicity, the study was stopped prematurely.
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PMID:Multicenter phase II study of spiroplatin. 157 59

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.
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PMID:Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. 159 14

In this retrospective study, 81 patients operated by craniotomy for a brain metastasis are reviewed. Mean age is 56.3 years and most of the patients are male (71.6%). Clinically, 79% of the patients present a focal semiology, most frequently with neuropsychologic disturbances (43%); epilepsy is found in 31% of the cases. Symptoms related to intracranial hypertension (vomiting and headache) are present in 43% of the patients. On C.T.-scan, there is a solitary metastasis in 89% and the most common intracranial location is the frontal lobe (33.3%). The most frequent primary neoplasms are: bronchial adenocarcinoma in 19%, squamous carcinoma of the lung in 11%, melanoma in 12% and unknown origin in 18%. The surgical removal (as judged by the surgeon) is total in 70%, subtotal in 19% and partial in 11%. Standard operative mortality (30 days after craniotomy) is 7.4%. The postoperative course (till the patients leave our department) is excellent in 58% (complete neurologic recovery), steady in 20% (stability of symptoms and neurologic examination) and bad in 22%, with worsening of the neurological deficits. Most of the patients (84% of the patients who survive more than 30 days after the craniotomy) had postoperative whole brain radiotherapy with a hypofractionned schedule (total doses of 15 to 40 Gy with fractions of 200 to 650 cGy). Ten patients had surgery alone. Mean survival is 10.2 months with a follow-up of 12 months to 10 years. Ten patients survived over 18 months and one is still alive almost 4 years after his craniotomy. In this study, the survival is not modified by the primary lesion's histology.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cerebral metastases. A study of a surgical series of 81 cases]. 160 35

Untreated and minimally pretreated solid tumor patients received alternating sequences of taxol and cisplatin. Sequential dose escalation of each agent using taxol doses of 110 or 135 mg/m2 and cisplatin doses of 50 or 75 mg/m2 resulted in four dosage permutations that induced grades 3 and 4 neutropenia in 72% to 84% and 50% to 53% of courses, respectively. Neutropenia was brief, and hospitalization for neutropenia and fever was required in 13% to 24% of courses. However, further escalation of taxol to 170 or 200 mg/m2 induced grade 4 neutropenia in 79% to 82% of courses. At the highest taxol-cisplatin dose level (200 mg/m2 to 75 mg/m2), the mean neutrophil count nadir was 98/microL, and hospitalization for neutropenia and fever was required in 64% of courses. The sequence of cisplatin before taxol, which has less antitumor activity in vitro, induced more profound neutropenia than the alternate sequence. Pharmacologic studies indicated that this difference was probably due to 25% lower taxol clearance rates when cisplatin preceded taxol. Although neurotoxicity was initially thought to be a potentially serious effect of the combination, mild to modest neurotoxicity occurred in only 27% of patients. Adverse effects also included myalgias, alopecia, vomiting, diarrhea, bradycardia, and asymptomatic ventricular tachycardia. Objective responses were noted in melanoma, as well as non-small-cell lung, ovarian, breast, head and neck, colon, and pancreatic carcinomas. Based on these results, the sequence of taxol before cisplatin at doses of 135 and 75 mg/m2, respectively, is recommended for phase II/III trials, with escalation of taxol to 170 mg/m2 if treatment is well tolerated.
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PMID:Sequences of taxol and cisplatin: a phase I and pharmacologic study. 167 80

To date, dacarbazine (DTIC) has been the most effective drug in the treatment of advanced metastatic melanoma, achieving response rates of up to 28% (mean, 21%). Multidrug responses were generally no better than those obtained using monotherapy. A quite promising clinical trial was conducted using the new nitrosourea fotemustine. A total of 19 patients presenting with advanced malignant melanoma (clinical stage IV according to the 1987 UICC classification system) underwent treatment involving a more rapid infusion of the drug and a reduction in the rest period from 5 to 3 weeks. This monotherapy with fotemustine yielded two complete responses and seven partial responses; in addition, four patients showed no change and six cases progressed after the induction cycle (median duration of response to date, 7.6 months, including four cases that have not relapsed). Fotemustine was well tolerated by the patients, with the only mild side effects being thrombocytopenia, leukocytopenia and easily controlled nausea/vomiting. Preclinical studies performed previously indicated that fotemustine inhibits enzymes involved in the ribonucleotide reduction pathway (i.e. DNA synthesis), whereby responding patients (n = 3) appeared to favor the thioredoxin reductase/thioredoxin electron transfer to ribonucleotide reductase, whereas non-responders (n = 4) expressed the alternate glutathione reductase/glutaredoxin mechanism. The 47% response rate obtained in these studies vs the 24% reported previously for fotemustine may reflect variations in enzymes in the ribonucleotide reduction pathway in different patients. However, the efficacy of fotemustine against advanced melanoma warrants more extensive trials of this drug, especially since the quality of life of the patients during and after chemotherapy was not severely affected.
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PMID:Positive phase II study in the treatment of advanced malignant melanoma with fotemustine. 174 55

Patients (n = 15) with metastatic malignant melanoma, hypernephroma, and colon carcinoma received a three-phase adoptive immunotherapy protocol: phase 1, 10(5) units (high-dose) interleukin-2 (IL-2) iv every 8 h or 1 mg/m2 continuous intravenous infusion; phase 2, 6.5 d rest + leukapheresis; phase 3, 4 d of high-dose IL-2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities of treatment included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Patients entering the trial were not malnourished, and mean plasma ascorbic acid concentrations before therapy were normal (36.3 +/- 14.2 mumol/L). Mean concentrations dropped by 80% after the first phase of treatment with high-dose IL-2 alone (to 7.4 +/- 4.5 mumol/L). Mean plasma ascorbic acid concentrations remained severely depleted (between 4.5 and 7.4 mumol/L) throughout the remainder of the 15-d treatment. Ascorbic acid concentrations became undetectable (less than 2.8 mumol/L) in 12/15 patients during this time. Blood pantothenate and plasma vitamin E concentrations remained within normal limits in all patients tested throughout the phases of therapy.
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PMID:Hypovitaminosis C in patients treated with high-dose interleukin 2 and lymphokine-activated killer cells. 196 85


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