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

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.
 ...
PMID:Phase I study of weekly 24-hour infusions of recombinant human interleukin-2. 326 71

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.
 ...
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.
 ...
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.
 ...
PMID:Intraperitoneal administration of interleukin-2 in patients with cancer. 349 95

Twelve patients were treated in a Phase I trial of purified human interleukin-2 (IL-2) derived from the JURKAT cell line (E.I. duPont Corp., Glenolden, PA, U.S.A.). The serum half-life, toxicity, and in vivo immunologic effects of IL-2 were studied in patients with cancer unresponsive to standard therapy and in patients with acquired immunodeficiency syndrome (AIDS). Patients received 0.25, 2.5, or 25 micrograms/kg IL-2 by bolus or 24-h continuous infusion on a weekly basis for 4 weeks. The serum half-life of JURKAT IL-2 in humans was approximately 6 min. At higher doses of IL-2 a second component of clearance with a half-life of 30-120 min was found. Acute toxicity was minimal and consisted of headache (6 of 12), nausea (4 of 12), malaise (6 of 12), and fever and chills (8 of 12). No evidence of pulmonary, hematologic, or renal toxicity or any evidence of autoimmune phenomena was detected. A transient hyperbilirubinemia was seen in two patients receiving 2 mg purified IL-2. No demonstrable effect on tumors or chronic immunodeficiency (AIDS) was seen. No consistent chronic immunologic effects (natural killer or lymphokine-activated killer activity, mitogen responsiveness, total lymphocyte counts, or change in the proportion of various mononuclear cell phenotypes as defined by monoclonal antibody) were seen on a week-to-week basis during or following therapy. Acute changes in lymphokine responsiveness, the ability to generate lymphokine-activated killers, and an increase in macrophages in the mononuclear population were noted following administration of 1-2 mg IL-2.
 ...
PMID:Systemic administration of interleukin-2 in humans. 633 35

The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.
 ...
PMID:Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects. 749 66

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.
 ...
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 use of alpha interferon (alpha IFN) and, more recently, of the purine analogues deoxycoformycin (dCF) and 2-chlorodeoxyadenosine (2-CdA) has dramatically improved the prognosis of patients affected by hairy cell leukemia (HCL). DCF has been shown to induce an higher and more durable response rate than IFN, with only moderate myelosuppression and relatively few side effects. In this paper, we report our experience with dCF in a series of 38 HCL patients who had progression of their disease after IFN therapy. Serum interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptors (sIl-2R) and Tumor Necrosis Factor alpha (TNF alpha) levels were also evaluated before, both during and after treatment in order to monitor clinical response. Two schedules of treatment were employed: 23 patients were treated with the EORTC protocol and the following 15 with the NCI regimen. The overall response rate was 94.7%; no significant differences in response rates were observed between the two schedules. In respect to toxicity, we recorded nausea and in two cases a cutaneous rash. Four patients experienced localized herpes zoster and one had a fungal pneumonia. Median overall survival after therapy is 38.5 months, 55 percent of patients enrolled in the EORTC schedule and 77% of those who received the NCI program are currently in CCR at 3 years. Serum IL-1 beta and sIL-2R levels significantly decreased after treatment, while no significant changes in serum TNF alpha levels were observed. In our study, dCF was confirmed as an effective agent in HCL, inducing an high response rate with only moderate side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Deoxycoformycin induces long-lasting remissions in hairy cell leukemia: clinical and biological results of two different regimens. 782 42

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.
 ...
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.
 ...
PMID:Phase II study of low dose cyclophosphamide and intravenous interleukin-2 in metastatic renal cancer. 796 Jun 3


<< Previous 1 2 3 4 5 6 7 8 9 Next >>