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)

Fifty-four patients with advanced malignancies were treated on this phase I trial of coumarin and cimetidine. The dose of coumarin was escalated, with three patients treated at each dose level, while the cimetidine dose was held constant at 300 mg four times daily. Patients received coumarin alone as a single daily oral dose for 14 days; on day 15, cimetidine was added and both drugs were continued until progression of disease. This trial was initiated with patients receiving coumarin at 400 mg daily and closed at 7 g daily with four of five patients on this dose experiencing nausea and vomiting. Treatment was generally well tolerated over a wide range of coumarin doses. Symptomatic side effects were few, mild, and usually self limited. Side effects included insomnia, nausea, vomiting, diarrhea, and dizziness. Two patients withdrew from therapy because of daily nausea and vomiting. Typically, nausea, vomiting, and dizziness occurred 2.5-3 hours after a dose of coumarin. In most patients, these side effects abated spontaneously with continuation of therapy. There was no significant hematologic or renal toxicity. Hepatotoxicity occurred in only one patient and was manifested by asymptomatic abnormal elevations of serum hepatic transaminases. This toxicity was reversible upon interruption of therapy. Objective tumor regressions were observed in six patients with renal cell carcinoma. Responses occurred at coumarin doses ranging from 600 mg to 5 g daily. Coumarin is a relatively nontoxic, oral, outpatient therapy that warrants further investigations for the treatment of human malignancies. Because of its low toxicity, there is potential for combining coumarin with chemotherapeutic and/or biological agents in an attempt to improve on efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies. 176 68

We studied the safety, tolerance, and clinical effects of the combined administration of subcutaneous recombinant human interleukin-2 and interferon alfa-2b in 54 patients with advanced cancer, for whom no effective standard therapy was available. Treatment courses consisted of a 2-day interleukin-2 pulse (14.4-18 million units (MU) m2/day), followed by 3.6 up to 4.8 MU/m2/day, 5 days per week, over 6 consecutive weeks and interferon alfa-2b at 3 up to 6 MU/m2, administered two-three times weekly for 6 weeks. Overall, patients received more than 90% of the projected dose of interleukin-2 and interferon alfa-2b, respectively. Of 54 evaluable patients (32 renal cell cancer, 12 melanoma, eight colorectal cancer, one B-cell lymphoma, one Hodgkin's disease), four complete responses occurred in patients with renal cell carcinoma, and a greater than 50% reduction in tumour size (partial response) in six renal cell carcinoma patients and one melanoma patient. Moreover, 21 patients (13 renal carcinoma) had stable disease. The median duration of response was 19 months (range 16-22 months) in complete responders. Clinical responses were associated with a mean peripheral blood eosinophil count of more than 1,000/microL (P less than 0.05 versus non-responders). Systemic toxicities included fever, chills, nausea, anorexia, and hypotension limited to WHO grades I and II in more than 80% of patients treated. No treatment-related deaths occurred. This combination of subcutaneously administered recombinant interleukin-2 and interferon alfa-2b has significantly diminished the side effects normally observed with high-dose intravenous recombinant interleukin-2, which requires admission to hospital. It has been shown to induce objective tumour regression in out-patients with progressive metastatic renal cell carcinoma and malignant melanoma.
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PMID:The out-patient use of recombinant human interleukin-2 and interferon alfa-2b in advanced malignancies. 179 91

We have studied the safety, tolerance, and clinical effects of the combined administration of subcutaneous recombinant human interleukin-2 and alpha-interferon in 34 patients with metastatic renal cell carcinoma who had undergone tumor nephrectomy. Treatment courses consisted of a 2-day interleukin-2 pulse (14.4 to 18.0 million IU/m2/d), followed by 3.6 to 4.8 million IU/m2/d, 5 days per week, over 6 consecutive weeks, and alpha-interferon at 3.0 to 6.0 million U/m2, administered 2 to 3 times weekly for 6 weeks. Patients received more than 90% of the projected dose of interleukin-2 and alpha-interferon, respectively. Of 34 patients with metastatic progressive renal cell carcinoma in this study, four had complete response and six had greater than 50% reduction in tumor size (ie, partial response). There were, in addition, 13 patients with stable disease. So far, all complete responses have been durable, with a median duration of 23+ months. Clinical responses were associated with a mean peripheral blood eosinophil count of more than 1,000/microliters (P less than .05). The predominant toxicities included fever, chills, nausea, anorexia, and hypotension, and were limited to World Health Organization grades 1 and 2 in more than 80% of patients treated. No treatment-related deaths occurred. This combination of subcutaneously administered recombinant interleukin-2 and alpha-interferon has significantly reduced the side effects normally observed with high-dose intravenous recombinant interleukin-2. It can induce objective tumor regressions in patients with progressive metastatic renal cell carcinoma. Unlike the intravenous schedules developed by Rosenberg and West, which require admission to hospital, all the patients in this study were treated in an outpatient setting.
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PMID:alpha-Interferon and interleukin-2 in renal cell carcinoma: studies in nonhospitalized patients. 194 23

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

Sixty-eight unselected patients with progressive metastatic renal cell carcinoma (RCC) were treated between March 1985 and November 1988 with continuous infusion floxuridine (FUDR). Thirty-seven percent of these patients had previously received and failed systemic treatment. Using implantable pumps for automatic drug delivery, FUDR was continuously infused for 14 days at monthly intervals. The starting dose was 0.15 mg/kg/d (intravenous [IV]; n = 61) or 0.25 mg/kg/d (intraarterial [IA]; n = 7); IV doses were increased or decreased in increments of 0.025 mg/kg/d as permitted by toxicity. Diarrhea (with or without mild abdominal cramping) and nausea/vomiting limited the FUDR IV infusion, and hepatic function abnormalities limited FUDR IA infusion. The use of a circadian-modified infusion schedule permitted high FUDR doses to be safely given as compared with a constant rate infusion schedule. Of 63 patients assessable for response, 56 received systemic FUDR infusion. Four complete responses (CRs; 7.1%); and seven partial responses (PRs; 12.5%) were observed (objective response rate, CR plus PR, 19.6 +/- 5.1% [95% confidence limits] ). The median objective response duration was 10.8 months (range, 1 to 18 months; mean, 9.4 +/- 1.6). Four additional patients had minor tumor responses (MRs; 7.1%). In a subgroup of seven assessable patients receiving hepatic arterial FUDR, we observed one CR and three PRs (57.2 +/- 42.8%). Overall, objective response (CR plus PR) was seen in a quarter of assessable patients treated, 15 of 63, while only 15 of the 63 assessable patients (25.4%) have had objective tumor progression. The median follow-up time for all 68 patients was 28 months (range, 1 to 42), and their median survival duration is 15 months (range, 3 to 37 months). Continuous infusion FUDR is an effective outpatient treatment for progressive metastatic RCC, producing durable tumor response and causing little toxicity.
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PMID:Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. 214 18

A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors.
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PMID:ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study. 219 39

We treated 17 patients who had progressive metastatic renal carcinoma with a combination of subcutaneous recombinant human interleukin-2 (administered every 12 hours, at 9.0 million IU/m2 on days one and two, followed by 1.8 million IU/m2, five days per week, over six consecutive weeks) and interferon-alpha 2b (given at 5 million U/m2 three times weekly, for six consecutive weeks). Treatment courses were repeated in patients presenting with stable or regressive disease after the six weeks of combination therapy (11 of 14 evaluable). Two and three of 14 evaluable patients achieved complete and partial remissions, respectively. Toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (WHO) fevers, chills, malaise, nausea/vomiting, and anorexia in more than two-thirds of the patients treated.
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PMID:Treatment of metastatic renal cell cancer patients with recombinant subcutaneous human interleukin-2 and interferon-alpha. 226 78

Prognostic factors for survival were analyzed retrospectively in 214 patients with brain metastases of the solid tumour type. The most frequent neurological signs and symptoms at diagnosis of cerebral involvement were headache-nausea-vomiting and focal weakness. Similar numbers of patients were found to have solitary metastasis and multiple lesions. Non-small cell lung cancer, small cell lung cancer, breast cancer, melanoma, and renal cell cancer comprised the majority of the primaries. Most patients received high-dose corticosteroids, while in a third, anticonvulsant agents were administered. Of 157 patients treated with radiation alone, or surgery with or without radiation, 110 experienced alleviation of symptoms or stabilisation of the disease. In 38 patients with a solitary lesion, craniotomy was carried out, either with or without postoperative radiation; the latter group showed the longest survival with a median of 37 wk. The remaining group of 73 patients with one brain metastasis had a median survival of only 15 wk. The 69 patients with multiple lesions who had been irradiated had a median survival of 15 wk, while that for 34 untreated patients was 7 wk. A short median survival of 11 and 13 wk, respectively, was observed in patients with concurrent progressive extracerebral disease and in those with progressive neurological symptoms regardless of treatment. It is concluded that in patients with a solitary brain metastasis without progressive extracerebral disease surgery should be considered the treatment of first choice aiming at a long-term survival with a good quality of life.
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PMID:Palliative care for brain metastases of solid tumour types. 246 70

Continuous long-term 5-fluoro-2'-deoxyuridine (floxuridine; FUDR) infusion frequently causes severe and dose-limiting gastrointestinal toxicity when administered at a constant rate at commonly prescribed dose levels. In preclinical studies, a circadian infusion pattern peaking late in the daily activity phase was better tolerated and had superior antitumor activity than a constant infusion against a transplanted tumor. Based upon these data and upon other chronobiological cytokinetic and pharmacologic considerations, we compared a circadian patterned variable rate infusion with a maximal flow rate in the late afternoon/early evening and minimum flow rate during the early morning hours to a constant rate infusion in 54 patients with widespread cancer. All FUDR infusions were administered using an implanted drug pump. In a pilot crossover study and a second randomized trial, patients with metastatic malignancies treated with equal dose intensities experienced less frequent and less severe diarrhea, nausea, and vomiting following variable rate infusion. In a third study, the dose intensity of variable rate infusion was escalated stepwise to determine the maximum-tolerated dose. Patients receiving time-modified FUDR infusion tolerated an average of 1.45-fold more drug per unit time while evincing minimal toxicity. FUDR infusion was found to have activity against progressive metastatic renal cell cancer (RCC). Increased dose intensity achieved by optimal circadian shaping may improve the therapeutic index of infusional FUDR and may help control malignancies that are refractory to conventional chemotherapy.
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PMID:Circadian patterning of continuous floxuridine infusion reduces toxicity and allows higher dose intensity in patients with widespread cancer. 253 Mar 18

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90


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