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)

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

Based upon the in vitro synergistic activity of interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma) observed in melanoma cells, we initiated a Phase II trial using the combination to determine the clinical antitumor efficacy in patients with advanced disease. Fifteen patients with metastatic malignant melanoma were given 2,000 micrograms of recombinant IFN-gamma (rIFN-gamma) (Biogen) intravenously (i.v.) over 10 min, followed by a 10 min i.v. injection of 30 million units of recombinant IFN-beta (rIFN-beta ser) (Triton) 3 x/week. Six patients had skin, soft tissue, nodal, or subcutaneous metastases, 6 had visceral disease only, and 3 had both. Seven patients had received prior treatment, including chemotherapy (6), radiotherapy (3), and/or immunotherapy (3). Side effects included typical IFN constitutional symptoms such as anorexia, fatigue, nausea, and myalgias, but were not dose limiting. The mean drop in the white blood cell count (WBC) following 1 month of therapy, compared to baseline, was 3.3 x 10(3)/mm2 (p = 0.002); the mean increase in SGOT was 24.1 U/l (p less than 0.001). One patient had a dose reduction for Grade III anorexia and fatigue which did not resolve with repeated treatment. One patient with liver metastases had radiographical and clinical stabilization of his disease for 1 year. No responses were seen. The median time to progression was 6 weeks. Two patients' tumors were evaluable in the human tumor colony forming assay (HTCFA) and were markedly sensitive to the antiproliferative effects of IFN combinations. Both patients, however, failed to respond clinically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of a combination of interferon-beta ser and interferon-gamma in patients with advanced malignant melanoma. 314 69

Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxy-daunorubicin), have shown antitumor activity in 23%-31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m2 p.o. on days 1,2,3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received greater than 2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean = 51 years). In 25 patients a performance status of 0-2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m2 i.v. days 1 and 8, Idarubicin 15 mg/m2 p.o. days 1, 2 and 3, and cyclophosphamide 500 mg/m2 i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3-16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I-II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination chemotherapy we have used has the following characteristics: easier administration (p.o. anthracycline, no risk of tissue extravasation), lower toxicity (cardiotoxicity, alopecia, and myelosuppression in particular), and a notable antitumor activity.
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PMID:Combination chemotherapy with 5-fluorouracil, oral Idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer--an open phase II study. 316 12

The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of the oral antiandrogen flutamide in 33 patients with metastatic breast cancer. Eight patients had received no prior systemic therapy for their metastatic disease and 13 had only one site of metastasis. Toxicity occurred in 18 of the 33 patients and was primarily gastrointestinal. It ranged in severity from mild to severe with 4 patients discontinuing treatment early because of nausea, vomiting, diarrhea or stomatitis. One response, of 8 weeks duration, was noted in 29 evaluable patients. We conclude that flutamide does not have meaningful antitumour activity in breast cancer and plan no further trials of the drug in this disease.
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PMID:Phase II study of flutamide in patients with metastatic breast cancer. A National Cancer Institute of Canada Clinical Trials Group study. 319 86

The toxic effects of protein A (Prosorba, IMRE Corporation, Seattle, WA) treatments given as part of an on-line plasmapheresis or off-line procedure were determined in a Phase I Study. Patients were randomized and treated 12 times either once per week or three times per week with a Prosorba column containing 50 or 200 mg protein A. Treated plasma volumes varied from 150 ml off-line to 2000 ml on-line. Seven patients having advanced metastatic breast adenocarcinoma patients were evaluated. All had advanced progressive disease that was resistant to chemotherapy and/or radiation therapy. Greater than 50% regression of measurable tumor volume occurred in four of seven patients; an additional patient responded with 33.5% regression. Two patients with only bony metastases demonstrated stable disease for a 60-day period. Side effects resulting from protein A treatments included transient fever, chills, rigors, and infrequently nausea, vomiting, diarrhea, episodic hyper and/or hypotension, bronchospasm, venospasm, headache, joint and tumor pain. Mild to moderate reactions were seen in all patients regardless of clinical response, but abated spontaneously or were controlled with pretreatment and/or post treatment with antipyretics and/or antihistaminics. The side effects decreased notably during the course of the week with the more intense reaction occurring during the first treatment of the week. Side effects occurred regardless of column size or volume of plasma treated. In the course of 12 treatments, anemia requiring transfusion developed in two of seven patients. Significant tumor regression was obtained in this group of patients with advanced disease. In light of the mild to moderate side effects and tumor regression in five of seven of the patients treated, protein A treatment merits further evaluation to determine the effectiveness of this treatment in breast adenocarcinoma.
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PMID:Toxicity following protein A treatment of metastatic breast adenocarcinoma. 334 17

Since 1924, when ependymomas were first classified as a distinctive glial neoplasm by Bailey, much has been published concerning these tumors, but there are important points of interest that are still not clear. In order to study more fully the clinical and pathologic characteristics of the ependymoma, we identified 62 patients with histologically proven neoplasms. Twenty-two were supratentorial, 21 were infratentorial, and 19 were intramedullary spinal cord tumors. These groups had mean ages of 17, 7, and 41 years, respectively, at the time of first symptoms. The presenting and accompanying symptoms were related to location and included headaches, nausea, visual changes, hemiparesis, and neck, back, and radicular pain. Neurological signs included papilledema, nystagmus, gait disturbance, cranial nerve palsies, altered mental status, paraparesis, and sensory dysfunction. Radiologic modalities of particular importance included computed tomography and myelography. Surgery and radiation therapy were the primary treatment modalities with median survival times from first symptoms being 92, 36, and 117 months for the above groups, respectively. Based on computer-generated survival curves, several characteristics significantly affected survival. These included tumor site, age, and neuraxis metastases. In patients with supratentorial tumors, cranial nerve palsies, microcystic changes, and mitotic figures were important, while in patients with infratentorial tumors, widened sutures, increased head circumference, age, epithelial features, and subependymal features significantly affected survival. Patients who had complete gross resection of a spinal cord tumor had no recurrences or mortality.
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PMID:Ependymomas: a clinicopathologic study. 335 39

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

In Columbus, OH, 46 patients with measurable metastatic colorectal cancer were treated with leucovorin (LV) 80 mg/m2/20 h intravenous (IV) infusion followed by 5-fluorouracil (5-FU) 400 mg/m2 IV bolus daily for three days and then once weekly. Many patients had liver (62%) and/or multisite metastases (53%), carcinoembryonic antigen (CEA) greater than 10 (76%), documented tumor progression before entry (51%), and tumor-related symptoms (36%), but also good performance status (84%). Prior therapy consisted of radiotherapy (RT) in 18%, chemotherapy in 22%, both in 4%, and none in 56%. There were 36% objective responses and 31% stabilization, which we believe is a significant change in the natural history of these patients. Median survival was 8 months. Improved survival was seen in patients with single- rather than multiple-site involvement. Decreasing CEA levels were seen in 59% (always in responders or patients with stable disease), and correlated with longer survival time (11.0 v 5.5 months, P = 0.01). Palliation of tumor related symptoms occurred in 75%, with or without antitumor effect. One patient with prior RT died of neutropenic sepsis after only the three-day load, so we now recommend only weekly therapy in previously radiated patients. Otherwise, toxicity was mild, manifest as weakness in 62%, nausea in 53%, or diarrhea in 47%, which was the most common dose-limiting side effect. The occurrence or absence of toxicity did not predict outcome. Because of equivalent efficacy, mild toxicity, and less expense, this regimen should be considered for patients who desire therapy.
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PMID:Leucovorin plus 5-fluorouracil: an effective treatment for metastatic colon cancer. 349 15

Fifteen consecutive patients with metastatic carcinoma who demonstrated bilateral adrenal metastasis on abdominal computed tomography (CT) were evaluated by the cosyntropin challenge test. Primary sites of tumors included lung, ten; colon, two; gastric, one; ovarian, one; and unknown primary, one. Bilateral adrenal enlargement was defined as greater than 1 cm on CT scan. Adrenal insufficiency was defined as a failure to increase serum cortisol by at least 5 micrograms/100 ml to a minimum of 15 micrograms/100 ml at either 30 or 60 minutes postcosyntropin. No patient had previously been on corticosteroids. All patients were questioned and examined for symptoms/signs of adrenal insufficiency. Five patients (33%) were found to have adrenal insufficiency based on the cosyntropin test. Of the clinical parameters evaluated, all five patients had nausea, anorexia, and orthostatic hypotension. The clinical onset of adrenal insufficiency was insidious; no patient experienced acute adrenal crisis. We conclude that adrenal insufficiency is not a rare occurrence in patients with metastatic cancer and bilateral adrenal involvement on CT scan.
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PMID:Prospective evaluation of adrenal insufficiency in patients with adrenal metastasis. 358 Oct 24

Cisplatin (25 to 120 mg. per m.2) was injected into the internal iliac arteries of 33 patients with locally advanced bladder cancer. Of the patients 9 were inevaluable for response to the cisplatin, since they began radiotherapy to the bladder before course 2 of cisplatin as part of a preplanned therapeutic approach. One patient received the treatment as postoperative adjuvant therapy, 1 did not return for followup and 1 with metastatic disease did not undergo repeat cystoscopy. Of 21 evaluable patients 3 (14 per cent) achieved complete remission, 12 (57 per cent) achieved partial remission, 2 (14 per cent) were stable and 4 (19 per cent) failed. The response rate was higher in patients receiving 100 to 120 mg. per m.2 per course than in patients receiving lower doses (all except 1 of whom received 60 or less mg. per m.2 per course) (86 versus 64 per cent) and it was higher in patients without prior radiotherapy or chemotherapy. The response rate in patients with previously untreated invasive transitional cell carcinoma was 88 per cent. Of the 33 patients 21 were alive at last followup, with a median duration of followup of 32 weeks. Toxicity was dose-related and local neurotoxicity was excessive at cisplatin doses of 100 to 120 mg. per m.2. Diabetic patients were particularly prone to have neurotoxicity. Other toxicity generally was not severe and consisted of ototoxicity, nephrotoxicity, myelosuppression, nausea, vomiting and diarrhea. Even elderly patients and patients with cardiac disease tolerated the treatment well. We plan to proceed with further intra-arterial cisplatin studies in which all patients except those more than 80 years old will be treated with an intra-arterial cisplatin dose of 90 mg. per m.2 per course combined with radiotherapy with or without cystectomy.
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PMID:Intra-arterial cisplatin for bladder cancer. 359 43


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