Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on recent preclinical data suggesting synergism between 5-fluorouracil (5-FU) and interferon alpha (IFN-alpha) and clinical activity of the combination therapy in colon cancer, 14 patients with advanced gastric cancer were treated with combination therapy of 5-FU and recombinant interferon alpha-2b (rIFN alpha-2b) (Intron A, Schering, Kenilworth, NJ, U.S.A.). The maximum tolerated dose was 5-FU 750 mg/m2/day given as a continuous infusion daily for 5 days followed by weekly bolus injection of the same initial daily dose, plus rIFN alpha-2b 5 X 10(6) U given subcutaneously 3 times weekly starting day 1 of 5-FU infusion. The dose-limiting toxicities were fatigue/weakness, diarrhea, and neurologic toxicities such as somnolence and confusion. The other common side effects were nausea, fever, leukocytopenia, thrombocytopenia, and the darkening of the skin. Of 13 evaluable patients, 4 had a partial response (duration 6, 14, 24, and 28 weeks). These data suggest that combination therapy of 5-FU plus rIFN alpha-2b is tolerable and has manageable side effects in patients with advanced gastric cancer. Further Phase II study will be needed to define the antitumor activity of this combination.
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PMID:Combination of 5-fluorouracil and recombinant interferon alpha-2B in advanced gastric cancer. A phase I study. 155 2

Sixty-four patients with hairy-cell leukemia (HCL) (61 had undergone prior splenectomy) were treated with alpha-2 interferon (Intron A, Schering Corp, Kenilworth, NJ) subcutaneously three times per week at a dosage of 2 X 10(6) U/m2. Three patients (5%) demonstrated a complete response (CR) with apparent eradication of hairy cells from the bone marrow, 45 patients (70%) showed a partial response (PR) defined as normalization of all three blood counts associated with decreased involvement in the bone marrow, and nine patients (14%) showed a minor response that included improvement in at least one blood count. Three patients had no response, three patients died before completing 1 month of therapy, and one patient refused further therapy after 1 month of therapy. The median platelet count returned to normal by the second month of treatment. The median hemoglobin returned to greater than 12 mg/dL by the fourth month of treatment, and the median granulocyte count to greater than 1,500/mu by the fifth month of treatment. Bone marrow biopsy analysis during interferon therapy demonstrated a decrease in median hairy-cell index by more than half. Transfusion of both RBCs and platelets were decreased within 4 months of initiating treatment. Serious infections, which averaged four per month in 16 of the 64 patients before interferon therapy, were rarely observed after the first month of treatment. Treatment-induced toxicity was mild, consisting primarily of influenza-like symptoms, fatigue, and minor skin disorders. Alpha-2 interferon therapy is highly effective in reversing the course of progressive HCL and should be considered the treatment of choice for a minimum of 12 months in patients who have progressive disease post-splenectomy.
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PMID:Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients. 351 80

Since interferon alfa-2b (Intron A) is useful as a single agent, it is important to determine if interferon can be combined with standard chemotherapy to improve both response and survival in patients with cancer. Using clonogenic assays, interferon was tested alone and in combination with cyclophosphamide (Cytoxan) or melphalan (Alkeran) using several dose and exposure schedules to evaluate cytotoxicity. In vitro, continuous-exposure interferon produced optimal cell kill. Maximum enhancement of cytotoxicity occurred with cyclophosphamide or melphalan pretreatment (1 hour) and/or simultaneous interferon treatment. Based upon these data, a phase I-II study was designed to determine the tolerance of cancer patients to a fixed dose of cyclophosphamide (150 mg/m2 p.o. daily X 4 days [days 2 to 5]) combined with increasing doses of interferon. Interferon was administered subcutaneously on treatment cycle days 1 to 5, plus days 8, 10, 12, 15, 17, and 19 of the 21-day regimen. Three patients had partial responses: one breast cancer, one angiosarcoma, and one myeloma (mixed). All patients reported mild flu-like symptoms, fatigue, and anorexia. Leukopenia occurred in all patients; three required treatment interruption to allow recovery. Eight patients had a fall in hemoglobin (mean decrease 1.4 g/dL). The combination of cyclophosphamide and interferon was safe and deserves further trial in cancer treatment. However, using this combination schedule, interferon doses greater than or equal to 5 X 10(6) IU were poorly tolerated and compromised administration of full-dose cyclophosphamide.
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PMID:Interferon alfa-2b-cyclophosphamide combination studies: in vitro and phase I-II clinical results. 376 44

To determine the maximum tolerated dose (MTD) of escalating doses of interferon-alpha-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1-5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1-5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3 x 10(6) U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2 x 10(6) U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1-5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
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PMID:A phase I study of recombinant human interferon alpha-2b combined with 5-fluorouracil and cisplatin in patients with advanced cancer. 788 58

We describe the case of a 56 years old man, who was operated on with abdominal wall skin malignant melanoma 5 years ago. He received postoperative DTIC + Intron A treatment. Five years later he presented with complaints of epigastric pain, melena, hematochezia, anorexia and fatigue. Upper gastrointestinal tract endoscopy showed a tumour mass in the duodeno-jejunal flexure and colonoscopy showed a tumour in the large bowel. Histology verified anaplastic carcinoma. The patient was operated on. We found metastases in the small and the large bowel The patient underwent resection of the jejunum and right hemicolectomy. We describe the different types of metastases of malignant melanomas symptoms, therapies and prognosis.
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PMID:[Late metastases of cutaneous malignant melanoma on the abdominal wall to the small and large bowel]. 1626 71