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)

The majority (85%) of patients receiving high dose Interleukin-2 (IL-2) experience gastrointestinal side effects, namely nausea, vomiting and diarrhea. In this article we describe four cancer patients that developed localized necrosis or perforation of the colon during IL-2 treatment. They represent 1.3% of patients (n = 315) or 0.9% of treatment courses (n = 452). All underwent surgical intervention and survived to leave the hospital. No common etiologic factor was apparent. Two patients were subsequently retreated with IL-2 without complication. Localized colonic necrosis or perforation is a rare complication associated with high dose IL-2 treatments. Aggressive surgical intervention is advocated and retreatment following recovery is safe.
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PMID:Colonic perforation. An unusual complication of therapy with high-dose interleukin-2. 326 82

Seventeen patients with refractory malignant tumors were treated with recombinant human interleukin-2 (IL-2) administered by weekly bolus intravenous (IV) injection in a phase I dose escalation trial. Patients received 10,000 to 1,000,000 U/m2 per injection over a course of 3 to 33 weeks. Toxicity was dose related and consisted primarily of fever, chills, nausea, and vomiting. Hypotension was observed at doses of 500,000 U/m2 or higher and in one instance was sufficiently severe to require pressors. No tumor regression was seen and all patients eventually developed progressive disease. Blood levels of cortisol, ACTH, prolactin, and growth hormone as well as the acute phase reactant C-reactive protein (CRP) increased after the administration of IL-2 in most patients. Serum IL-2 levels in excess of 250 U/mL were detected five minutes after an IV injection of 1,000,000 U/m2, after which the levels declined with a half-life of approximately 25 minutes. No alteration in lymphocyte surface phenotype or enhancement in natural cell-mediated cytotoxicity against natural killer (NK)-sensitive and resistant tumor cell lines was observed when these parameters were measured weekly just before the IL-2 injections. However, a dramatic but transient decline in circulating lymphocytes and NK activity was noted within hours of receiving IL-2. This effect was independent of fever and was not abrogated by pretreatment with ibuprofen or metyrapone. The majority of patients developed serum IgG antibodies of IL-2 detectable with a sensitive enzyme-linked immunosorbent assay (ELISA) and a nitrocellulose dot blot assay. The development of anti-IL-2 antibodies was not associated with symptoms suggestive of serum sickness, reductions in serum complement levels, or deterioration in lymphocyte tumoricidal activity. This investigation provides insight into the in vivo actions of this potent biological response modifier and will assist in the design of future studies with IL-2 administered alone or in conjunction with other treatment modalities.
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PMID:Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease. 348 80

We have administered 11 to 64 doses of recombinant interleukin-2 (IL-2) ranging from 10,000 to 300,000 U/kg, given three times daily as a bolus infusion through an indwelling Tenckhoff catheter, to seven patients with melanoma, ovarian carcinoma, or colorectal carcinoma. The total IL-2 dose ranged from 800 to 3800 X 10(3) U/kg. Side effects included fever, chills, nausea, vomiting, diarrhea, and major weight gain presumedly related to a capillary leak syndrome. Total weight gain ranged from 5.1 to 17.4 kg and was associated with the development of both peripheral edema and ascites. Marked eosinophilia was noted. Serum IL-2 levels were maintained at 10 to 35 U/mL for up to eight hours following intraperitoneal administration of IL-2. Increases from less than 10(4) cells/mL of a 2-L peritoneal wash to more than 10(6) cells/mL were noted in peritoneal exudate cell yields. Lysis of the natural killer target K562 increased from undetectable levels to as high as 125 lytic units per 10(6) cells. Proliferative capacity to IL-2 increased as much as 30-fold in peritoneal exudate cell yields. In addition, 70% to 80% of the mononuclear cells were T cells (Leu 4+) with intraperitoneal phenotype treatment. A single patient with pulmonary and hepatic metastases showed marked decrease in these lesions with intraperitoneal IL-2 treatment. The other patients treated intraperitoneally with IL-2 did not have significant (greater than 50%) reduction in tumor volume. These findings indicate that the intraperitoneal route of IL-2 administration may allow the in vivo development and expansion of lymphoid cells with antitumor activities.
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PMID:Intraperitoneal administration of interleukin-2 in patients with cancer. 349 95

The toxicity of recombinant Interleukin-2 (IL-2) was studied in patients with acquired immunodeficiency syndrome (AIDS) or persistent lymphadenopathy syndrome (LAS). Increasing doses of the drug from 10(3) Units/m2 to 10(6) U/m2 were given as an intravenous bolus injection. At the high-dose levels some minor effects, such as fever up to 39.5 degrees C, chills, malaise or vomiting, were observed. The administration of 10(6) U/m2 as a 4-hour infusion showed identical results. No particular alterations of laboratory parameters were found. At the high-dose level the serum concentration of neopterin, which is released from macrophages after interferon gamma stimulation, was significantly (p less than 0.001) elevated above pretreatment levels. The clinical observation of daily infusions of 10(6)/m2 for 14 days revealed the same side effects. All patients developed lymphocytosis and eosinophilia. Two patients had suffered from severe diarrhoea for several weeks presumably due to cryptosporidiosis. In both cases diarrhoea ceased under the treatment with IL-2 and did not occur in the following two months.
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PMID:Preliminary clinical observations with recombinant interleukin-2 in patients with AIDS or LAS. 387 44

Both chemotherapy and interleukin-2 and/or interferon-alpha produce objective responses in a proportion of advanced malignant melanoma patients. While duration of response to chemotherapy is short, i.e. usually below 4 months, immunotherapy has resulted in a small number of long-lasting remissions in patients with metastatic melanoma. In two consecutive phase II trials in a total of 67 patients, we assessed the potential synergism between both modalities, i.e. chemo- and immunotherapy. Treatment consisted of intravenous (i.v.) carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice (i.v. bolus over 30 min) at 3-week intervals, or 4 cycles of DTIC (220 mg/m2 i.v. 3 days), cisplatin (DDP, 35 mg/m2 i.v. 3 days), carmustine (BCNU, 150 mg/m2 i.v. cycles 1 and 3) and tamoxifen (TAM, 20 mg oral/daily) at 3-week intervals. Chemotherapy was followed by immunotherapy with combined subcutaneous (s.c.) interleukin-2 (rIL-2) and SC interferon-alpha 2 (rIFN-alpha). Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CRs) with a median duration of 19 months (range 13-26+). Partial remissions (PRs) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5-14) months. Among 27 patients who received DTIC/DDP/BCNU/TAM and rIL-2/rIFN-alpha, there were 3 (11%) complete remissions and 12 (44.5%) partial remissions. Duration of complete and partial remissions ranged from 9+ to 13+ (median, 11+), and 5 to 15+ (median, 7+) months, respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 18 days following start of CBDCA/DTIC and DTIC/DDP/BCNU, respectively. 10 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side effects; malaise, fever, chills, nausea/vomiting, diarrhoea, anorexia and arthralgias were most frequent, but were spontaneously reversible after ending rIL-2/IFN-alpha. A mean 87 and 88% of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths. The sequential combination of chemotherapy and rIL-2 plus rIFN-alpha had at least additive therapeutic activity against metastatic malignant melanoma. The schedules produced long-lasting remissions and were tolerated well overall. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.
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PMID:Chemoimmunotherapy of advanced malignant melanoma: sequential administration of subcutaneous interleukin-2 and interferon-alpha after intravenous dacarbazine and carboplatin or intravenous dacarbazine, cisplatin, carmustine and tamoxifen. 764 14

The safety, tolerance, and clinical effects of combined therapy with recombinant interferon-alpha (IFN-alpha) and interleukin-2 (rIL-2) administered subcutaneously for 2 courses of 4 weeks each, with 4 weeks interval between courses, given as outpatient therapy have been assessed in 10 patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML). All patients were previously treated with conventional chemotherapy and 3 failed to respond to IFN-alpha administered prior to our study. Median duration of disease from diagnosis was 36 months. Seven patients were in first chronic phase and the other 3 were in blast crisis, second chronic phase, and relapse post-bone marrow transplantation (BMT), respectively. Hematological response (median follow-up 16 months) was observed in 9 patients, with a decline in number of white blood cells and platelets. Elimination of Ph1 was observed in the patient who relapsed post-BMT with complete elimination bcr/abl RNA by polymerase chain reaction. Rebound lymphocytosis and eosinophilia were observed in most of the patients. Toxicity was acceptable. The main adverse effects were fever, chills, fatigue, anorexia, nausea, and vomiting. The side effects were reversible and no interruption of treatment was required. There was no treatment-related hospitalization or deaths. These data suggest that simultaneous subcutaneous IFN-alpha and rIL-2 home therapy is feasible, reasonably well tolerated, and potentially beneficial in CML patients. These observations may have important implications for the treatment of minimal residual disease following allogeneic and autologous marrow transplantation.
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PMID:Treatment of chronic myelogenous leukemia with recombinant human interleukin-2 and interferon-alpha 2a. 792 12

Thirteen patients with metastatic renal cancer were treated in a phase II trial with interleukin-2, 21.6 million IU/m2 intravenously daily for five days on two consecutive weeks, starting 3 days after the administration of low dose cyclophosphamide 350 mg/m2 intravenously. Treatment cycles were repeated every 21 days. No responses were seen (95% Confidence Interval: 0-22%). The most common toxicities were fever, fatigue, hypotension, nausea/emesis, and myalgia/arthralgia. There were 11 episodes of Grade III toxicity including Grade III hypotension in 7 patients. Because of the significant toxicity and the lack of observed response, the study was discontinued. Cyclophosphamide and interleukin-2 at the dose and schedule used in this study has considerable toxicity and is unlikely to improve on response rates previously seen with other IL-2 based regimens in metastatic renal cancer.
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PMID:Phase II study of low dose cyclophosphamide and intravenous interleukin-2 in metastatic renal cancer. 796 Jun 3

Four normal adult dogs received two consecutive weekly cycles of human recombinant interleukin-2 (IL-2) by continuous infusion for 4 days/week. The dose of IL-2 given to each dog was 3 x 10(6) units m-2 day-1. Toxicities consisted of mild vomiting, diarrhea, and lethargy to varying degrees in all the dogs. These side-effects were reversed when the treatment was discontinued. Fever, tachypnea, and weight gain were not seen. A marked lymphocytosis and eosinophilia developed in all dogs after completion of each course of IL-2 (resulting in a more than sevenfold increase in each cell type) and persisted for more than 1 month in some. Fresh peripheral blood lymphocytes (PBL) obtained during this lymphocytosis mediated enhanced in vitro lysis of a natural-killer-cell-sensitive canine tumor cell line (CTAC). The in vitro proliferative responses of these same PBL to IL-2 could be detected earlier, progressed faster, and involved more cells than PBL tested prior to IL-2 infusion. Thus, a relatively well-tolerated regime of IL-2 in dogs can induce dramatic increases in lymphocyte numbers and activation, which is associated with augmentation of their in vitro antitumor reactivity. The clinical effectiveness of this immunotherapeutic approach remains to be tested in tumor-bearing dogs where it could serve as a relevant large-animal model for immunotherapy of cancer with IL-2.
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PMID:Clinical and immunological effects of human recombinant interleukin-2 given by repetitive weekly infusion to normal dogs. 804 33

Emesis and nausea are common toxicities seen during high-dose interleukin-2 (IL-2) therapy (720,000 IU/kg i.v. every 8 h). A growing list of randomized studies have documented the efficacy of ondansetron, a potent antagonist of the 5-hydroxytryptamine3 receptor, in preventing acute chemotherapy-induced emesis and nausea. However, no study has evaluated the efficacy of ondansetron in preventing IL-2-induced emesis and nausea. This double-blinded, randomized trial was performed to compare the antiemetic and antinausea efficacy of ondansetron with that of droperidol, a butyrophenone, in patients receiving high-dose IL-2 on protocols at the National Cancer Institute. Ondansetron or droperidol was given intravenously, 30 min prior to the first dose of IL-2 and then every 8 h for the duration of IL-2 treatment. No significant differences were seen between the two agents in complete freedom from emesis (p2 = 0.51), level of nausea (p2 = 0.17), antiemetic treatment failure (p2 = 0.89), and time to first emetic episode (p2 = 0.44). Equivalent doses of IL-2 were administered on each arm of the study, with a similar incidence of liver dysfunction (p2 = 0.15) and diarrhea (p2 = 0.64). Finally, there was no significant difference in the response rates to metastatic disease in either arm of the antiemetic study (p2 = 0.67), and these response rates were similar to those in other patients treated under immunotherapy protocols in the Surgery Branch of the National Cancer Institute with high-dose IL-2. We conclude that droperidol is equally effective in preventing emesis and controlling nausea when compared with ondansetron for patients receiving high-dose IL-2.
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PMID:A randomized double-blinded comparison of the antiemetic efficacy of ondansetron and droperidol in patients receiving high-dose interleukin-2. 808 60

We treated 14 patients with progressive metastatic colorectal cancer, using a combination of subcutaneous recombinant human interleukin-2 (4.8 x 10(6) IU/m2 three times daily on days 1 and 22, and twice daily on days 2 and 23, followed by 2.4 x 10(6) IU/m2 twice daily on days 3-5, 8-12, 24-26, and on 5 consecutive days per week, starting day 29), recombinant human interferon-alpha 2a (5.0 x 10(6) U/m2 thrice weekly), and 5-fluorouracil (750 mg/m2 i.v. bolus on days 15-19, and at weekly intervals thereafter, with a 1-week off-therapy interval every 4 weeks). Therapy was continued until disease progression occurred. Four (29%) and 8 (57%) evaluable patients achieved partial remission and stable disease, respectively; median response duration was 5.9 months. Toxicity of this regimen was moderate; the most common side effects were thrombocytopenia, leukopenia, nausea/vomiting, anorexia, malaise and fevers in all patients, along with diarrhea (63%) and mucositis (54%). Less than 10% of patients developed WHO grade IV toxicity; no toxic deaths occurred. Efficacy of this combination was not substantially different from alternative 5-fluorouracil-based regimens.
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PMID:Treatment of metastatic colorectal cancer patients with 5-fluorouracil in combination with recombinant subcutaneous human interleukin-2 and alpha-interferon. 819 11


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