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)

Biological response modifiers (BRMs) have greatly modified the immunotherapy of tumors. Interleukin-2 (IL-2) has brought about metastasis regression in some cases of malignant tumors, however, when given systemically, it results in high toxicity. More recently, the subcutaneous administration of IL-2 (combined with alpha-interferon, alpha-IFN) seems to be capable of offering the same chances of therapeutic response, but this time with a lower level of toxicity. The Authors report an evaluation of toxicity in 22 patients treated with a combination of IL-2 + alpha-IFN i.m. with or without chemotherapy. The side-effects present in the majority of cases were: fever, diarrhea and asthenia. Approximately 50% of the patients had nausea/vomiting, mucositis, skin rashes, and slight leukopenia. The following side-effects were noted to a much lesser degree, thrombocytopenia, alterations in hepatic and dizziness and cystitis. Only one patient reached 4th degree toxicity, with mucositis, asthenia and skin rash. All the other patients received the treatment without suspensions for toxicity. Biological evaluations will enable us to determine in the future, the cases which can benefit from therapeutic intensification and thus it would seem opportune at this time to use therapy with acceptable toxicity.
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PMID:Evaluation of toxicity in 22 patients treated with subcutaneous interleukin-2, alpha-interferon with and without chemotherapy. 128 42

Eleven patients with hairy cell leukemia (HCL) were treated with YK-176 (2'-deoxycoformycin) at a dose of 5 mg/m2 by intravenous injection every week or every other week. Patients received a median of eight (range 4-19) injections of YK-176. Five patients had previously been untreated, four of whom had massive splenomegaly. Six patients had previously been treated, four with interferon-alpha (IFN-alpha) or IFN-alpha and chemotherapy and two with prednisolone. Two patients had had splenectomies. Five patients achieved complete remission (CR) and six, partial remission (PR) according to WHO criteria (remission rate 100%, 95% confidence interval (CI) 74-100%). All six neutropenic patients recovered > 1,500/microliters neutrophils, six of seven anemic patients recovered > 12.0 g/dl hemoglobin and five of nine thrombocytopenic patients recovered > 100,000/microliters platelets following the treatment. According to the response criteria for HLC, five patients achieved CR, two PR and four minor response. The overall remission (CR + PR) rate was 64% (95% CI 35-85%). The CR and PR have lasted from > 30 to > 718 days (median, > 281 days) so far with no relapses. Of four patients previously treated with IFN-alpha, two achieved CR and one, PR. All patients were alive with a median survival time of > 290 days from treatment (range > 50- > 763 days). The treatment was generally well tolerated. Mild to moderate nausea, vomiting, appetite loss and general fatigue were experienced in two patients, skin rash in one and a transient fever in three. YK-176 was a highly active agent in the treatment of HCL.
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PMID:Treatment of hairy cell leukemia with deoxycoformycin (YK-176). The Deoxycoformycin (YK-176) Study Group. 129 57

Thirty-four patients with previously untreated advanced non-small-cell lung cancer were treated with a combination of polychemotherapy and recombinant interferon. Chemotherapy consisted of cyclophosphamide, 400 mg/m2, epidoxorubicin, 50 mg/m2, and cisplatin, 40 mg/m2 (CAP) i.v. on day 4; recombinant alpha 2b interferon (r alpha 2b IFN) was given i.m. daily at the dose of 3-5 MU from days 1 to 7. The treatment was repeated every 4 weeks. In the 32 eligible patients the overall response rate was 19.3% (95% C.L. 7.4-37.4%). Non-hematologic toxicity consisted formerly in flulike symptoms and fatigue complained of by 37.5% and 31.2% of patients, respectively, and vomiting reported in 68.7% of patients; grade III-IV myelotoxicity was observed in 12.5% of cases. In no case was the toxicity life threatening. The median overall actuarial survival and progression-free survival were 37 and 20 weeks, respectively. This study indicates that the combination of CAP chemotherapy and r alpha IFN is feasible and active in the treatment of advanced non-small-cell lung cancer.
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PMID:Combination chemotherapy and interferon alpha 2b in the treatment of advanced non-small-cell lung cancer. The Italian Lung Cancer Task Force (FONICAP). 185 86

Sixty-two patients with biopsy-proven, measurable disseminated malignant melanoma received either the combination IFN-alpha 2A with BCNU (30 patients) or the combination cimetidine with BCNU (32 patients) in parallel noncomparative Phase II trials. From patients receiving IFN-alpha 2A plus BCNU, we observed a 7% response rate: 1 complete response (CR) and 1 partial response (PR) (soft tissue disease with durations of 6.9 and 11.5+ months, respectively). Median time to progression (MTP) was 1.8 months and median survival time (MST) was 3.8 months. Myelosuppression and a flu-type illness were the most common toxicities. From patients receiving cimetidine plus BCNU, the response rate was 16%: 4 PRs (soft tissue disease, 3.8 months; visceral, 2.1, 4.0+, and 9.7 months) and 1 CR (soft tissue, 14.3+ months). MTP and MST were 1.9 and 5.5 months, respectively. Myelosuppression and nausea/vomiting were the most common side effects. Although each of these regimens had great conceptual allure, neither offered any durable impact on the natural history of disseminated malignant melanoma. Nevertheless, alternative combinations of biological response modifiers (BRMs) and BRMs with biochemical modulators or cytotoxic agents may provide some useful alternatives for further clinical investigations.
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PMID:Phase II trial of recombinant leukocyte A interferon (IFN-alpha 2A) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the combination cimetidine with BCNU in patients with disseminated malignant melanoma. 202 22

Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are cytokines with profound immunobiological effects on T-cell and natural killer (NK) cell activity; IL-2 also induces lymphokine-activated killer (LAK) cell cytotoxicity in humans. Both lymphokines induce antineoplastic activity against several refractory tumors. This Phase I study of 50 patients assessed the toxicities, maximally tolerated dose (MTD), effects on certain immune effector cells, pharmacokinetics of IL-2, and development of antibodies to the combination of subcutaneously administered IL-2 and intravenously administered beta-IFN. Fever was common. Indomethacin reduced the incidence and severity of fever and was necessary to prevent it from becoming dose-limiting. Hypotension occurred but never required pressors or produced complications. Constitutional symptoms, local skin toxicity at the site of IL-2 injection, generalized desquamation, eosinophilia, nausea, and vomiting were also observed. One patient had reversible renal dysfunction. Two patients experienced drug-related dyspnea without evidence of capillary leak syndrome; neither required intubation. Fluid retention and cardiotoxicity were not observed. The MTD was 5 x 10(6) U/m2 s.c. of IL-2 and 2 x 10(6) U/m2 i.v. of beta-IFN when given in combination. Enhancement of in vivo NK cell cytotoxicity and proliferation of T4+, T8+, and NK cells occurred. In vivo induction of LAK cell cytotoxicity was observed in three patients. Four patients developed nonneutralizing anti-IL-2 IgG antibodies, but none developed antibodies to beta-IFN. Peak IL-2 serum levels typically occurred 4 h following drug administration. Serum levels were within a factor of 3 of the peak level in the period studied, 1-6 h postinjection. No complete responses occurred. One patient with rectal cancer and one with transitional cell carcinoma each had a partial response, and 13 other patients (5 with renal cell, 4 with colorectal, and 4 other cancers) had stable disease. Induction of NK cell cytotoxicity was seen more commonly in patients with stable disease than in those with progressive disease. Combined administration of these agents is feasible with acceptable toxicity, and Phase II trials are warranted.
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PMID:Phase I trial of recombinant interleukin-2 and recombinant beta-interferon in refractory neoplastic diseases. 278 53

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

Staphylococcal enterotoxin A (SEA), the most common cause of food poisoning, is capable of stimulating human T lymphocyte proliferation at concentrations as low as 10(-13) to 10(-16) M. SEA also induces the lymphokines interleukin 2 (IL 2) and interferon gamma (IFN gamma) at similarly low concentrations. HPL cultures were stimulated with SEA in the presence of antibodies to IL2 to determine the possible role of this lymphokine in its potent mitogenic effects. Polyclonal and monoclonal antibodies to human IL 2 blocked SEA-induced mitogenesis. Treatment of cultures with higher concentrations of SEA overcame the anti-IL 2 blockage, corresponding to induction of higher concentrations of IL 2. Blockage of HPL mitogenesis by anti-IL 2 antibodies also resulted in inhibition of IFN gamma production, which is dependent on IL 2. Neutralizing monoclonal antibody to IFN gamma failed to block SEA-induced proliferation. The data indicate that the induction of IL 2, but not IFN gamma, is a requirement for SEA induced lymphocyte proliferation. SEA food poisoning and IL 2 therapy for cancer result in similar toxic symptoms, characterized by malaise, fever, nausea or vomiting, and diarrhea. The similarity between SEA and IL2 toxic effects, the fact that SEA is a potent inducer of lymphokines such as IL 2, and the fact that IL 2 induction is a prerequisite for the mitogenic effects of SEA raises the intriguing question of the role of lymphokines such as IL 2 in SEA-induced food poisoning.
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PMID:Potent mitogenic activity of staphylococcal enterotoxin A requires induction of interleukin 2. 313 70

Both interferon-alpha (IFN-alpha) and alpha-difluoromethylornithine (DFMO) have shown modest activity as single-agent therapy in the treatment of malignant melanoma. Several investigators have demonstrated true synergism in vitro of the combination of DFMO and IFN-alpha against human tumor cells, including melanoma. We have investigated this combination in 17 patients with malignant melanoma in a Phase I trial. Patients were treated with 4 or 6 g/m2/day of oral DFMO in 3 divided doses for 11 days, followed by a 3-day rest period. Concomitant administration of 1.5, 3.0, 6.0 or 9.0 x 10(6) U/m2 IFN-alpha intramuscularly was given. The maximum tolerated dose was 4 g/m2/day of DFMO plus 6 x 10(6) U/m2/day of IFN-alpha. Dose-limiting toxicity occurred in 3 of 3 patients receiving 9 x 10(6) U/m2 IFN-alpha and consisted of leukopenia, fatigue, and weight loss. Other toxicities were mild and included reversible hearing loss, diarrhea, nausea, and vomiting. Three responses were seen, including one partial response (PR) of soft tissue metastases, one PR of lung and liver, and one complete response of liver metastases without clearance of carcinomatous meningitis. A Phase II trial has been initiated based on these encouraging results.
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PMID:A phase I trial of recombinant interferon-alpha and alpha-difluoromethylornithine in metastatic melanoma. 313 43

Twelve children ages 3-15 years with relapsed acute lymphocyte leukemia (ALL) were treated over 25 days by intravenous or intramuscular administration of interferon-alpha n1 (IFN-alpha n1). Single doses ranged from 2.5 to 15 MU/m2, total doses from 60 to 200 MU/m2. Serum pharmacokinetics were determined following administration of two different doses. Calculation of area under serum concentration curve (AUC) values showed increased AUC with increased dose. Mean AUC (h x U/ml) ranged from 735 to 3986 at doses of 2.5 and 15 MU/m2, respectively, when given intramuscularly. AUC for i.v. and i.m. administration were similar. Side effects reported most commonly were fever and chills in 11 of 12 patients, nausea/vomiting in 7, mild lethargy in 3, and injection site pain in 4 of 9 treated i.m. Reversible hepatotoxicity occurred in the 3 patients receiving the highest doses, 10 then 15 MU/m2. Three patients had clinically significant bleeding associated with mildly increased coagulation studies and an additional three patients had increased coagulation parameters without bleeding. Four patients were considered to have stable disease; one treated at the highest dose level had clearance of peripheral blasts but remained in bone marrow relapse. IFN-alpha n1 as used in this study produced detectable blood levels with associated side effects. A Phase II intramuscular trial is recommended.
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PMID:Interferon-alpha n1 in children with recurrent acute lymphocytic leukemia: a phase I study of pharmacokinetics and tolerance. 316 26

A phase I study with human lymphoblastoid alpha-interferon (IFN-alpha) was conducted in 31 patients with malignant tumors. IFN-alpha was administered by intravenous drip infusion, intramuscular injection or local injection. In each patient, the dose was increased in 6 steps from 3 X 10(6) IU/body up to 54 X 10(6) IU/body for the purpose of investigating the safety, optimal regimen, pharmacokinetics and antitumor effect. The following findings were obtained: 1) Fever as a side effect was most frequently (in about 80%) found. However, the temperature did not exceed 40 degrees C in most cases and, on the next day, spontaneously fell to normal. 2) The dose-limiting factors (DLF) may include the subjective symptoms of anorexia, general fatigue and nausea/vomiting and the objective symptom of pancytopenia. 3) The maximum tolerated dose (MTD) was estimated to be between 36 X 10(6) and 54 X 10(6) IU/body per dose. 4) As for the route of administration, the intramuscular one was considered most suitable on the basis of the plasma concentration profile of INF-alpha. It was therefore concluded that the drug may be further submitted to a phase II study which is to be conducted with due consideration of its safety.
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PMID:[Phase I study of human lymphoblastoid alpha-interferon on malignant tumor]. 396 61


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