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)

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

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

A phase I trial of Roussel-Uclaf recombinant human interleukin 2 (IL 2) was performed on 31 cancer bearing patients of the Institut Gustave-Roussy, Villejuif, and the Institut Curie, Paris. This study allowed to define a schedule for administration of IL 2 in continuous infusion over 5 day cycles. This schedule is manageable in patients without major visceral failure. It is reproducibly feasible in conventional medical oncology units, without specialized intensive care facilities. Toxicities, although numerous, are acceptable for IL 2 doses below 24,000,000 IU/m2/day. There is a close relationship between secondary effect severity and IL 2 doses received. Main toxicities were: fever with chills, fatigue and general discomfort in 23 patients, nauseas and vomiting in 12, diarrhea in 10 and cutaneous rashes with erythema and dermal vascularitis in 13. One peculiar feature of this study was the minimal occurrence of manifestation related to leaky capillary syndrome prominant in other studies. Oliguria, functional renal failure and edema were observed in only 4 patients with functionally unique kidney. Five patients had severe anemia, 2 grade III thrombocytopenia, 1 grade IV hepatic cytolysis, 4 severe confusion episodes and 2 hypothyroidism with anti-thyroid microsome auto-antibodies. All these toxicities were reversible after withdrawal of IL 2 treatment. During this phase I trial, 3 therapeutic objective responses were observed, all 3 occurring in patients with metastatic melanoma treated with IL 2 doses equal to, or above 16,000,00 IU/m2/d. Recombinant IL 2 Roussel-Uclaf thus can be administered through a simple, manageable and efficient regimen.
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PMID:[Phase I trial of a recombinant human interleukin 2. Results in patients with disseminated solid tumors]. 182 63

Twenty-nine patients with biopsy-confirmed metastatic melanoma (17) or metastatic renal cell carcinoma (12) were treated with escalating doses or recombinant human interleukin-2 (IL-2) administered as weekly 24-h intravenous infusions. Patients received from 3 to 12 x 10(6) C.U./m2 (18-72 x 10(6) I.U./m2) weekly over a treatment period of 1 to 16 weeks, with a median of eight weekly cycles administered. Patients in all treatment groups experienced non-life-threatening systemic side effects consisting of fever, nausea, vomiting, fluid retention, and diarrhea. Grade III hypotension was seen in four of six patients (67%) at 12 x 10(6) C.U./m2, and represented the dose-limiting toxicity. Grade IV hypotension occurred in 1 of 14 patients at 6 x 10(6) C.U./m2; no other grade IV toxicities were observed. Grade III fever occurred in 3 of 11 patients (27%) treated at 3 x 10(6) C.U./m2, 3 of 14 patients (21%) at 6 x 10(6) C.U./m2, and 3 of 6 patients (50%) at 9 x 10(6) C.U./m2. An objective response was observed in 3 of 28 evaluable patients (10%): 1 complete response and 1 partial response in renal cell cancer, and 1 partial response in a melanoma patient. We conclude that for future studies, the recommended dose of IL-2 given as a weekly 24-h infusion is 9 x 10(6) C.U./m2 and that a low rate of objective tumor response can be obtained in patients with melanoma and renal cell carcinoma using this regimen.
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PMID:Weekly 24-hour continuous infusion interleukin-2 for metastatic melanoma and renal cell carcinoma: a phase I study. 201 99

Sixteen patients with metastatic melanoma were treated with N-methylformamide (NMF), a polar-planar compound with in vitro cytotoxic and differentiating properties. Sixteen patients were evaluable for toxicity and 14 for response. The initial four patients received an intravenous bolus of NMF 800 mg/m2 daily for 5 consecutive days every 28 days. Because of excessive gastrointestinal toxicity, the dose was reduced to 700 mg/m2/day for the subsequent 12 patients. Two patients had immediate adverse effects from NMF; one had a grand mal seizure and the other developed severe abdominal pain. Nausea, vomiting and abdominal pain were dose-limiting. Transient elevation of liver function tests occurred in all patients. Myelosuppression was not observed. There were no objective responses among 14 evaluable patients (95% confidence limits 0-20%). One patient with pulmonary metastases had a minor response lasting 13 months. Median time to progression of disease was one month. NMF in these doses and schedule lacks clinical efficacy in the treatment of metastatic melanoma.
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PMID:Phase II trial of N-methylformamide in patients with metastatic melanoma. 202 91

Fifty-one patients with metastatic melanoma were treated with cisplatin, vinblastine, and bleomycin. Of the 50 evaluable patients, 11 (22%) achieved an objective response, including three complete (6%) and eight partial (16%) responses. Four of the 11 responding patients had previously received dacarbazine; the remaining patients had received no prior chemotherapy. Responses were noted in cutaneous and lymph node sites as well as visceral metastases. However, with one exception, all responding patients with visceral involvement had lung metastases. Response durations were brief and toxicity was substantial. Nadir leukocyte counts less than 0.5 X 10(9)/L occurred in 28% of the patients. Debilitating neurotoxicity, primarily paralytic ileus, and severe nausea and emesis were experienced by 24% of the patients. The combination of cisplatin, vinblastine, and bleomycin is not sufficiently beneficial to warrant its use in metastatic melanoma.
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PMID:Cisplatin, vinblastine, and bleomycin in the treatment of metastatic melanoma: a phase II study of the Southeastern Cancer Study Group. 241 Jan 20

Twenty-two patients with metastatic melanoma were treated with a chemotherapy regimen consisting of two cycles of induction therapy with vinblastine, bleomycin, and cisplatin, followed by maintenance therapy with dacarbazine and dibromodulcitol. A 17% response rate was noted in this patient group, with a median survival of 40 weeks. Objective responses were limited to cutaneous, nodal, pulmonary, and one adrenal site of metastatic disease. Toxicity was acceptable and was limited to myelosuppression and nausea with emesis. Further study appears warranted to define the optimal treatment plan for metastatic melanoma.
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PMID:A phase II trial of vinblastine, bleomycin, and cisplatin induction followed by dacarbazine and dibromodulcitol maintenance in the treatment of metastatic melanoma. A follow-up study of twenty-two patients. 246 Oct 74

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and human leukocyte interferon (IFN-alpha) have synergistic anti-tumor activities in vivo in B 16 melanoma and in vitro against several human cancer cell lines. We have, therefore, carried out a phase I combination study with DFMO plus alpha interferon in the following manner: DFMO was maintained at a steady dose for the first four levels, 1.5 g/m2 every 6 hr. IFN-alpha was given in 100% increments ranging from 0.4 X 10(6)U/m2 to 3.2 X 10(6)U/m2 i.m. daily. At the fifth dose level both IFN-alpha and DFMO were raised by 100 and 50% respectively. From levels one through four the combination was well tolerated with no dose interruptions required because of G.I. toxicity or myelosuppression. However, at dose level 5, one-third of the patients required dose cessation and decrease due to nausea, vomiting and diarrhea. We conclude that for phase II studies the maximal tolerated dose is 3.2 million units of IFN-alpha/m2 and 1.5 g/m2 of DFMO every 6 hr. Of 12 patients with metastatic melanoma, 2 had partial remissions lasting 58+ and 36+ weeks. Two additional patients had minor responses lasting 29 and 32+ weeks. Minor responses were observed in a patient with colon carcinoma and a patient with renal carcinoma. The clinical activity of the combination is currently being pursued in a phase II study among patients with metastatic malignant melanoma.
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PMID:Difluoromethylornithine and leukocyte interferon: a phase I study in cancer patients. 309 71

Sixteen patients with metastatic melanoma or metastatic renal cell carcinoma were treated with six weekly 24-hour infusions of recombinant interleukin-2. At least three patients were treated at each dose, beginning at 3.0 mU/m2 for 24 hours each week for 6 weeks. Subsequent patients were treated at 4.5, 6.0, 8.0, and 10.0 mU/m2 for 24 hours. The incidence of diarrhea, rigors, rash, edema, and symptomatic hypotension was positively correlated with dose level. Symptomatic hypotension was dose limiting at the 10-mU/m2 level. Fever, nausea, and vomiting were seen at each dose level and could not be correlated with dose level. Lymphopenia and eosinophilia were observed at the completion of each 24-hour infusion, and an increase in peripheral blood absolute lymphocytes and eosinophils was observed over the 6-week treatment period. No thrombocytopenia was observed. No change in delayed-type hypersensitivity (type IV) as determined by skin testing could be demonstrated at any dose level. Natural killer cell cytotoxicity of peripheral blood lymphocytes increased over the treatment period, but the increase was unrelated to dose level in the range studied. One minor response was documented in a patient with renal cell carcinoma.
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PMID:Phase I study of weekly 24-hour infusions of recombinant human interleukin-2. 326 71

Seventy-nine patients with metastatic melanoma received chlorozotocin (150 mg/m2) every 6 weeks. Two complete and five partial responses were observed: 18% in patients who had not previously received chemotherapy and 6% in previously drug-resistant patients. Dose-limiting toxic effects were vomiting and myelosuppression.
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PMID:Phase II study of chlorozotocin in malignant melanoma: a Southeastern Cancer Study Group report. 621 Dec 34


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