Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to evaluate the feasibility of 5-fluorouracil (FU) treatment modulated by (R,S)-leucovorin (LV) and interferon alpha (IFN alpha) in patients with advanced colorectal cancer, we conducted a phase I trial with increasing doses of subcutaneous IFN alpha (3 x 1 x 10(6) U, 3 x 3 x 10(6) U, 3 x 3 x 10(6) U, 3 x 5 x 10(6) U and 3 x 10 x 10(6) U/week) and 500 mg/m2 LV i.v. as a 2-h infusion with 600 mg/m2 FU i.v. as a midpoint injection. Unacceptable side-effects occurred in all 3 patients at the highest dose level of IFN alpha, while toxicity was tolerable at 3 x 5 x 5 x 10(6) U IFN alpha/week. Thus, this dose was defined as the maximal tolerable dose for IFN alpha in combination with FU and LV. In a subsequent phase II study a total of 83 treatment courses (median: 2.8, range: 2-10) were administered to 30 evaluable patients. Side-effects were acceptable with no WHO grade IV toxicities. Grade III toxicities consisted in thrombopenia (2/30), stomatitis (2/30), diarrhoea (3/30) and nausea/vomiting (4/30). After a median observation time of 17 months (range: 8-22 months), no complete remission was observed and 9 patients experienced a partial response lasting for a median of 6.6 months (range: 3-13+ months), for an overall response rate of 30% (95% confidence interval: 15%-49%). These results show that the described regiment of FU doubly modulated by LV and IFN alpha is active in colorectal cancer and can be safely administered in an out patient setting with acceptable toxicity. Thus, this regimen is suitable to be used for further evaluation in clinical trials.
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PMID:Double modulation of 5-fluorouracil by high-dose leucovorin and interferon alpha 2b in advanced colorectal cancer: a phase I and a phase II study of weekly administration. 812 62

Interferon-alpha (IFN-alpha) exhibits a clear platelet reductive effect in patients with essential thrombocythemia as well as in other chronic myeloproliferative disorders with thrombocytosis. In a total of 51 patients with chronic myeloproliferative disorders with thrombocytosis we analyzed the effect of IFN-alpha in respect to platelet reduction, remission rates, induction- and maintenance dosage, long term tolerance and side effects. According to our classification CML 6, chronic mega-karyocytic granulocytic myelosis 5, essential thrombocythemia 26 and polycythemia vera 15 patients were treated. Treatment consisted of induction with 3 or 5 MU IFN-alpha daily followed by a maintenance therapy with 3 or 5 MU thrice weekly. Platelet reduction was found in all patients, CR (platelets < 450 G/l) in 78%. Within 2 months of induction therapy, CR in patients treated with 5 MU IFN daily was found in 75% compared to 52% in patients treated with 3 MU IFN daily. Dosage reduction in maintenance periode caused an increase of platelets to more than 450 G/l in 39% of patients. Out of 40 Philadelphia-negative chronic myeloproliferative disorders treated for more than 3 months in 10 patients treatment was disrupted after 5 to 18 months because of the following side effects: nausea, fatigue, vertigo, fever, headache, diarrhea, anorexia, heartburn, hairloss, myalgia, and thrombocytopenia. Due to the mutagenic effect of alkylating cytostatics and Radiophosphorus, IFN-alpha treatment represents a first line strategy for chronic myeloproliferative disorders with thrombocytosis especially in younger patients who are symptomatic and in those who suffered from episodes of bleeding or thrombosis.
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PMID:[Interferon therapy in essential thrombocythemia]. 827 65

In the present study, we have updated our results with chemotherapy, alpha-interferon, octreotide and combinations of treatment modalities in patients with malignant endocrine pancreatic tumor (EPT). In our patient material of 134 EPT, 92 subjects had malignant tumors as evidenced by the presence of metastases or growth into adjacent organs. Seventy-eight patients had liver metastases. Streptozotocin plus 5-fluorouracil produced objective responses in 17/31 (54%) patients with a median duration of response of 23 months. The use of 5-HT3-antagonists as antiemetics has dramatically improved the quality of life during treatment by reducing the frequency of nausea to only 12.5%. The objective response rate to alpha-interferon (alpha-IFN) treatment, given as first-line treatment in 29 patients and after chemotherapy in 28 patients, was 51% (29/57) with a median duration of response of 20 months. Octreotide, which is still used as third-line treatment in most patients, produced significant biochemical responses in 6/19 (31%) patients with a median duration of 16 months. Combinations of alpha-IFN plus chemotherapy and a alpha-IFN plus octreotide in a small number of patients might indicate additive or synergistic effects. The median survival from start of treatment in the 92 malignant cases was 56.5 months, and for those with liver metastases (n = 78) at start of treatment 50 months. In conclusion, there are at least three effective therapies for malignant EPT and by combining them simultaneously or consecutively, a median survival of more than four years can be obtained.
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PMID:An update of the medical treatment of malignant endocrine pancreatic tumors. 839 32

Immunotherapy with subcutaneous rIL-2 and alpha IFN was administered to stage D3 prostate cancer patients after failure of secondary treatment with oral estramustine phosphate. Of a total of 15 patients, 2 are in partial response, with estramustine maintained after 44+ and 36+ weeks, respectively. Response to estramustine was observed initially in 7 of 13 patients, with a median duration of 12 weeks (range 8-20). No response to estramustine was observed in the remaining 6 patients. After the failure of estramustine, 13 patients were treated with immunotherapy. After the first cycle, progression of disease no therapy was given to those patients. A reduction of PSA levels was observed during the first cycle in 2 patients (15.3%); levels subsequently increased during the second cycle of treatment. A partial response was observed in 4 patients (30.7%), with a reduction of PSA levels in 3. The duration of response was 28 and 32 weeks in 2 patients who survived after failure for 18 and 21 weeks, respectively. Two patients are still alive, with continued partial response at 62+ and 42+ weeks. Side effects were represented mainly by a flu-like syndrome, associated with fever and nausea in all patients. The serum concentration of IL-10 was measured in 8 patients under study and in 11 matched controls. Levels higher than mean + 2D of controls before, during, or after immunotherapy were correlated with treatment failure, whereas levels below 6 ng/ml were encountered among the patients who showed a clinical response and a reduction of PSA during treatment. Within the limitations of this pilot study, it appears difficult to distinguish between a spontaneously slowly progressing disease and a true response to therapy.
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PMID:Salvage immunotherapy with subcutaneous recombinant interleukin 2 (rIL-2) and alpha-interferon (A-IFN) for stage D3 prostate carcinoma failing second-line hormonal treatment. 861 53

The use of OKT3 as an immunosuppressive agent is accompanied by increased cytokine production and constellation of side effects collectively termed cytokine release syndrome (CRS). Pentoxifylline (PTF) inhibits synthesis of some cytokines, and has been shown to attenuate CRS when administered before OKT3. In this double-blinded, placebo-controlled study, 46 renal allograft recipients were randomized to receive either PTF (800 mg q 8 hr for at least 24 h) p.o. or placebo, along with methylprednisolone (7 mg/kg), diphenhydramine, and acetaminophen, prior to beginning OKT3 as therapy for acute rejection. Patients were observed, and symptoms scored semiquantitatively. Despite the presence of therapeutic PTF levels (721 +/- 726 ng/ml), the frequency and severity of side effects (fever, chills, headache, neurocortical symptoms, dyspnea, nausea, vomiting, diarrhea) did not differ between treatment groups. Likewise PTF did not affect renal function or immunologic response to OKT3, with similar graft and patient survival in both groups. Plasma levels of TNF alpha, IFN gamma, IL-6, and IL-8 increased as predicted following OKT3 administration, without significant differences between PTF and placebo groups. In this controlled, multicenter trial, pretreatment with oral PTF was ineffective in attenuating OKT3-related CRS in renal allograft recipients.
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PMID:Pentoxifylline does not prevent the cytokine-induced first dose reaction following OKT3--a randomized, double-blind placebo-controlled study. 861 Mar 83

A total of 29 patients with stage IV colorectal cancer were entered into a phase II trial of bolus interleukin-2 (IL-2) and interferon-alpha (IFN alpha) (3 x 10(6) U/m2 of each cytokine given i.v. q8h x 15 doses and repeated in 2 weeks). Immunologic parameters measured on isolated peripheral blood lymphocytes revealed increased activated T cells with upregulated natural killer and lymphokine-activated killer activity. Among 24 evaluable patients, there were 4 partial responses (17%) of short duration ( < or = 6 months). Three of the responding patients had been refractory to prior chemotherapy. Overall median survival in the 24 evaluable patients was 18.5 months. Therapy necessitated an inpatient setting, with the most common toxicities being hypotension, hepatic insufficiency, fever, hypocalcemia, nausea/vomiting, and renal insufficiency. There were two treatment-related deaths. Because neither IL-2 nor IFN alpha alone has significant activity against colorectal cancer, the responses observed in this study suggest a potential synergistic effect between the two cytokines. However, the toxicity and short duration of response without survival benefit do not support the routine use of this regimen as a therapeutic modality for this tumor histology.
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PMID:A phase II trial of interleukin-2 and interferon-alpha in the treatment of metastatic colorectal carcinoma. 868 Jun 53

Patients with advanced adenocarcinomas of the pancreas have an exceptionally poor prognosis. Modest activity has been demonstrated with single agents (response rates of 25% at best with 5-fluorouracil [5-FU] and mitomycin). Better results have not been obtained by combination chemotherapy. Improvements in the palliation have been achieved by treatment with 5-FU, folinic acid (FA), and interferon-alpha-2A (IFN-alpha) weekly in the context of a phase II trial. Of 57 evaluable patients, eight (14%) had a partial response (PR), eight (14%) a minor response (MR), and 28 (49%) had no change of disease (NC). The median survival time was 10 mo for patients with progressive disease. Twenty-two out of 36 patients with tumor-related pain whose tumors were affected in terms of PR, MR, and NC became free of pain during treatment. Fever (56%), nausea (37%), and diarrhea (33%) were common toxicities observed. Therefore, biochemical modulation of 5-FU with FA and IFN-alpha shows some positive effects in the treatment of pancreatic cancer with moderate toxicity.
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PMID:Chemotherapy in advanced pancreatic cancer. 912 72

A prospective phase II trial was carried out to define the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon alpha-2b (IFN-alpha) in combination with intravenous administration of vinblastine (VLB) in patients with metastatic renal cell cancer (RCC). Thirty-one patients with advanced RCC who had received no prior biochemotherapy were treated with IL-2 4.5 MU x 2/24 h thrice weekly for 2 weeks, IFN-alpha 3 MU/24 h thrice weekly (alternating days) for 2 consecutive weeks and VLB 4 mg/m2 every 3 weeks. Patients were to have a 1-week rest period after each 2 weeks of therapy with cytokines. Treatment was repeated every 3 weeks. Maximum duration of treatment was 1 year. Treatment was administered on an outpatient basis. There were 4 complete (12.9%) and 8 partial responses (25.8%), with an overall response rate of 38.7%. The median duration of response was 6.5 months. Responses were seen in lung, lymph nodes, bones, liver and other tumor metastases. Toxicity was mild to moderate, consisting of fever, anorexia, malaise and nausea-vomiting in > 80% of patients. Hypotension and transient alopecia occurred in > 20% of patients. Liver enzyme elevation was frequently observed. Treatment-induced eosinophilia occurred in the majority of patients, while in 52% of patients granulocytopenia grade II and grade III did not require dose modification of drugs. Transient inflammation and local induration at the injection sites was observed in the majority of patients. None of the patients experienced major VLB-related toxicity and no toxic deaths occurred. This three-drug combination immunochemotherapy may be a promising regimen with modest toxicity in advanced RCC.
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PMID:An outpatient phase II study of subcutaneous interleukin-2 and interferon-alpha-2b in combination with intravenous vinblastine in metastatic renal cell cancer. 942 69

To evaluate the efficacy of methotrexate (MTX)-5-fluorouracil (5-FU), cisplatin (CDDP), and interferon-alpha-2b(IFN alpha-2b) combination therapy, we conducted a clinical pilot study in patients with locally advanced hepatocellular carcinoma (HCC). Sixteen patients, who had received no prior treatment for the HCC, with portal tumor thrombosis in the main trunk or in the major branch were enrolled in the study. IFN alpha-2b (3 x 10(6) units) was injected subcutaneously 3 times per week. After a bolus administration of MTX (30 mg/m2), CDDP (75 mg/m2) and thereafter 5-FU (750 mg/m2) were given weekly by intrahepatic arterial infusion. In 15 eligible patients, there were 1 complete response (CR) and 6 partial responses (PR) with a response rate of 46.7%. Median survival of the 15 patients was 7 months, and the 2-year survival rate of CR and PR patients was 57.1%. There was severe transient hematologic toxicity. More than grade 2 nausea/vomiting was noted in > 50%. In conclusion, the IFN alpha-2b combination chemotherapy demonstrated good response in patients with locally advanced HCC. This treatment should be tried in a controlled study.
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PMID:Clinical pilot study of intrahepatic arterial chemotherapy with methotrexate, 5-fluorouracil, cisplatin and subcutaneous interferon-alpha-2b for patients with locally advanced hepatocellular carcinoma. 942 74

Management of advanced malignant mesothelioma (MM) still requires innovative systemic therapy as its prognosis is poorly affected by currently available chemotherapy. The combination cisplatin and alpha-interferon (alpha-INF) has synergistic antitumoral activity in preclinical models and interesting activity in phase I-II clinical trials. Weekly CDDP (60 mg/m2) and alpha-IFN (3 MUI/d: d1-d4) in combination was tested in a previous phase I-II study in 23 MM patients, with a 36% objective response rate (ORR). A trial with higher doses of alpha-IFN in the same combination schedule was conducted to explore an incrementalist hypothesis. Thirty patients with MM received the same CDDP dose (60 mg/m2/w) and doubled doses of alpha-IFN (6 MUI/d: d1-d4). The treatment protocol consisted of two cycles of 4 weeks on/4 weeks off followed by two shorter cycles of 3 weeks on/3 weeks off, in the absence of life-threatening toxicity or progressive disease. All patients were evaluable for toxicity. The main treatment-limiting side-effects were digestive intolerance (nausea, vomiting) and severe asthenia. Antitumoral efficacy was not increased (ORR = 27%). Haematological and neurological toxicities were moderate and manageable. The antitumoral activity of the CDDP-alpha-IFN combination with higher doses of the latter is similar to our previous experience, but tolerance issues make it a poorer choice for eventual comparative trials, or as a standard therapeutic indication.
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PMID:Higher doses of alpha-interferon do not increase the activity of the weekly cisplatin-interferon combination in advanced malignant mesothelioma. 947 Aug 55


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