Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase II study to test the toxicity and the efficacy of a weekly combination of Mitoxantrone, 5-Fluorouracil and L-Leucovorin (MFL) was carried out in 43 patients with metastatic breast cancer. Chemotherapy consisted of mitoxantrone 4 mg/m2, 5-fluorouracil 375 mg/m2, and L-leucovorin 100 mg/m2 on day 1, weekly. Patient characteristics were: median age 53 years (range 36-65); estrogen receptor (ER) status was known in 26 patients and of these 15 (57.7%) patients were ER-positive and 11 (42.3%) ER-negative. Of the 43 patients, 25 (58.1%) and 18 (41.9%) patients had received prior adjuvant chemotherapy and prior adjuvant endocrine treatment, respectively. MFL was administered to 22 (51.1%) patients as first line chemotherapy for advanced disease, while 21 (48.9%) patients had received 1 to 2 cytotoxic regimens for metastatic disease. The dominant sites of metastases were: soft tissue in 11 (25.5%) patients, bone in 8 (18.6%) patients and viscera in 24 (55.9%). All patients were assessable for toxicity: only 8 patients experienced WHO grade 3 leukopenia. Thrombocytopenia, diarrhea, stomatitis, and nausea/vomiting were negligible. Anemia and alopecia were not observed. Thirty-nine patients were assessable for response: overall response rate was 28.2% (complete response 7.7% and partial response 20.5%). Median duration of response was 12 months (range 6-34). Patients with no prior anthracyclines had a 42.1% response rate compared to 15% in patients who had received anthracyclines. Median overall survival of the 43 patients was 6 months (range 1-34). Weekly MFL is a well-tolerated and a moderately effective regimen for the treatment of metastatic breast cancer.
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PMID:Phase II study of weekly mitoxantrone, 5-fluorouracil, and leucovorin in metastatic breast cancer. 794 11

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.
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PMID:[Phase I study of 5-fluorouracil and l-leucovorin]. 845 86

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM. From January 1988 until April 1994, 88 patients with recurrent or metastatic AGC were randomly received 5FU, EPI, MMC with (group A) or without (group B) LV. Between the two arms of the study no difference was noticed in sex, performance status, primary site of tumor, and lymph node metastases. Therapy included group A (5FU 600 mg/m2/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m2/day, i.v. bolus, on days 1 and 29, MMC 10 mg/m2/day, i.v. bolus, on day 1) and group B (the same as group A plus LV 200 mg/m2/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there were two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significantly higher number of patients achieving stable disease was observed in group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). There were more patients with progressive disease in group A 25 (59%) than in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted in mean duration of response: group A, 15.8 (6-31) weeks; and group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients from disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not evaluable because they abandoned therapy after the first cycle. Toxicity was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically different when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required more commonly in group B. We conclude that the response rate was increased in the schedule with the addition of LV, at the cost of increased toxicity and with no difference in survival. A randomized trial comparing FEM-LV with new generation regimens would determine whether the addition of LV qualifies FAM equally active with these.
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PMID:5-Fluorouracil, epirubicin, and mitomycin C versus 5-fluorouracil, epirubicin, mitomycin C, and leucovorin in advanced gastric carcinoma. A randomized trial. 882 83

A 54-year-old patient with primary cerebral lymphoma was treated with two 4-weekly cycles of high-dose intravenous cytarabine (12 g/m2) and methotrexate (3 g/m2). The administration of the first course proceeded without notable complications. Before the administration of methotrexate in the second cycle blood cell counts and chemistry showed no abnormalities except for slightly increased alkaline phosphatase and gamma-glutamyl-transpeptidase levels which was attributed to diphantoin comedication. The patient developed symptoms of acute renal failure 7 h after methotrexate infusion which resulted in a very high serum methotrexate level (39.84 micromol/l) at 20 h after infusion. Rescue therapy was intensified: the leucovorin dosage was increased (1,200 mg continuous i.v. infusion every 24 h) and combined with thymidine rescue therapy (8 g/m2 per day continuous i.v. infusion every 24 h). Urine alkalinization was increased and diphantoin therapy was stopped. Leucovorin eye drops and mouth washes were started 5 days after methotrexate administration to prevent conjunctivitis and mucositis as a result of high methotrexate levels (>2.4 micromol/l). In spite of the fact that serum methotrexate levels remained persistently higher than 0.1 micromol/l for 12 days, the patient experienced no further short-term systemic toxicity except for anaemia (grade 3 according to NCI Common Toxicity Criteria). After day 12 intensified rescue therapy and the frequency of alkalinization were decreased to standard procedures and stopped on day 19. It is concluded that i.v. administration with high-dose methotrexate can result in unpredictable acute toxicity. In our patient, acute methotrexate toxicity was treated successfully by intensification of classical leucovorin rescue therapy in combination with thymidine infusion. In addition, leucovorin mouth washes and eye drops may have prevented mucositis and conjunctivitis, respectively.
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PMID:Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure. 1145 8

We report a case in which weekly paclitaxel (TXL) administration was effective for gastric cancer with malignant ascites. TXL (80 mg/m2) was infused over 1 hour after short premedication on an outpatient basis. Administration was continued for 3 weeks followed by 1 week rest. The patient was a 49-year-old woman who suffered from non-resectable gastric cancer, staged intraoperatively as having severe lymph node metastasis and malignant ascites. As an outpatient treatment, she was first treated with 5-fluorouracil combined with high-dose Leucovorin for 4 cycles. However, she complained of abdominal fullness and ascites, and received weekly TXL administration as the second line treatment. The ascites had completely disappeared 3 months after administration. The toxic events were anemia (grade 1) and alopecia (grade 2). No major adverse effects such as hypersensitivity reaction, leukopenia or peripheral neuropathy were observed.
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PMID:[Effective weekly paclitaxel administration for gastric cancer with malignant ascites--a case report]. 1235 53

Two phase III studies revealed an oral UFT/Leucovorin (LV) regimen, in which the drugs are taken for 28 consecutive days every 35 days, which proved to be equivalent to an infusional 5-fluorouracil/LV regimen for metastatic colorectal cancer (CRC). The weekday-on/weekend-off schedule for UFT, which is taken for 5 consecutive days followed by 2 drug-free days,has been reported to be safe and to have good feasibility. In the present study, we investigated the weekday-on/weekend-off schedule for UFT/LV in 54 patients with CRC. The median administration period was 8 months. Ten patients (19%) showed grade 2 or more severe adverse reactions. One of them had grade 3 diarrhea and anorexia. Grade 2 anemia was observed in 9 cases (19%) and grade 2 leucopenia was in 2 cases (4%). Myelotoxicity was mild. These results suggested that the adverse reactions in the weekday-on/weekend-off schedule for UFT/LV are less severe than the conventional UFT/LV schedule reported previously. Antitumor effects and survival benefits of the two schedules should be evaluated by a phase III study.
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PMID:[Feasibility of weekday-on/weekend-off oral UFT/Leucovorin schedule as postoperative adjuvant chemotherapy for colorectal cancer]. 1653 13

The objective of this update is to give an overview of the effects of dietary nutrients on the structure and certain functions of the brain. As any other organ, the brain is elaborated from substances present in the diet (sometimes exclusively, for vitamins, minerals, essential amino-acids and essential fatty acids, including omega- 3 polyunsaturated fatty acids). However, for long it was not fully accepted that food can have an influence on brain structure, and thus on its function, including cognitive and intellectuals. In fact, most micronutrients (vitamins and trace-elements) have been directly evaluated in the setting of cerebral functioning. For instance, to produce energy, the use of glucose by nervous tissue implies the presence of vitamin B1; this vitamin modulates cognitive performance, especially in the elderly. Vitamin B9 preserves brain during its development and memory during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters. Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), provided it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin improves cerebral and cognitive functions in the elderly; it frequently improves the functioning of factors related to the frontal lobe, as well as the language function of those with cognitive disorders. Adolescents who have a borderline level of vitamin B12 develop signs of cognitive changes. In the brain, the nerve endings contain the highest concentrations of vitamin C in the human body (after the suprarenal glands). Vitamin D (or certain of its analogues) could be of interest in the prevention of various aspects of neurodegenerative or neuroimmune diseases. Among the various vitamin E components (tocopherols and tocotrienols), only alpha-tocopherol is actively uptaken by the brain and is directly involved in nervous membranes protection. Even vitamin K has been involved in nervous tissue biochemistry. Iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxidase), and for the synthesis of neurotransmitters and myelin; iron deficiency is found in children with attention-deficit/hyperactivity disorder. Iron concentrations in the umbilical artery are critical during the development of the foetus, and in relation with the IQ in the child; infantile anaemia with its associated iron deficiency is linked to perturbation of the development of cognitive functions. Iron deficiency anaemia is common, particularly in women, and is associated, for instance, with apathy, depression and rapid fatigue when exercising. Lithium importance, at least in psychiatry, is known for a long time. Magnesium plays important roles in all the major metabolisms: in oxidation-reduction and in ionic regulation, among others. Zinc participates among others in the perception of taste. An unbalanced copper metabolism homeostasis (due to dietary deficiency) could be linked to Alzheimer disease. The iodine provided by the thyroid hormone ensures the energy metabolism of the cerebral cells; the dietary reduction of iodine during pregnancy induces severe cerebral dysfunction, actually leading to cretinism. Among many mechanisms, manganese, copper, and zinc participate in enzymatic mechanisms that protect against free radicals, toxic derivatives of oxygen. More specifically, the full genetic potential of the child for physical growth ad mental development may be compromised due to deficiency (even subclinical) of micronutrients. Children and adolescents with poor nutritional status are exposed to alterations of mental and behavioural functions that can be corrected by dietary measures, but only to certain extend. Indeed, nutrient composition and meal pattern can exert either immediate or long-term effects, beneficial or adverse. Brain diseases during aging can also be due to failure for protective mechanism, due to dietary deficiencies, for instance in anti-oxidants and nutrients (trace elements, vitamins, non essential micronutrients such as polyphenols) related with protection against free radicals. Macronutrients are presented in the accompanying paper.
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PMID:Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. 1706 9

The patient was a 75-year-old man who was admitted because of diarrhea and anemia. Endoscopic examination revealed advanced sigmoid colon cancer. Serum CEA levels were markedly elevated. In July 2007, surgery was performed, but the sigmoid colon cancer was unresectable. After surgery, the patient was treated with chemotherapy and concurrent radiotherapy. The chemotherapy consisted of oral UFT (420 mg/body/day)and Leucovorin (75 mg/body/day) administered for 6 weeks. Radiotherapy at 2 Gy/day was administered 30 times (total dose 60 Gy). The tumor decreased slightly in size and serum CEA levels also decreased. The patient refused surgery as an additional therapy. In August 2007, we started combination chemotherapy using oral S-1 (100 mg/body/day, day 1-14) and intravenous CPT-11 (140 mg/body/day, day 1 and 15) as one course for 4 weeks. After 4 courses, serum CEA levels were normal, the sigmoid colon cancer was not found by endoscopy and a biopsy specimen revealed no malignant cells. Moreover, after 8 courses, the tumor disappeared, as confirmed by computed tomography (CT) and positron emission tomography-CT, representing a complete response. Chemoradiotherapy using UFT and Leucovorin, and chemotherapy consisting of S-1 and CPT-11 as an additional therapy may be effective for treating unresectable advanced sigmoid colon cancer.
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PMID:[A case of effective chemotherapy using S-1 and CPT-11 following chemoradiotherapy with UFT and Leucovorin for unresectable advanced sigmoid colon cancer]. 2033 98

A 65-year-old woman was referred to our hospital for examination of anemia. Colonoscopy showed a type 1 tumor in the ascending colon with nearly complete stenosis that was diagnosed as a tubular adenocarcinoma. Computed tomography (CT) revealed swelling of the regional, periaortic, and celiac lymph nodes and lymphangitis carcinomatosa. The patient was diagnosed as having Stage IV ascending colon cancer, and neoadjuvant chemotherapy was administered to avoid non-curative resection. The patient was treated with cetuximab and oxaliplatin, Leucovorin, and 5-fluorouracil( mFOLFOX6) combination chemotherapy. After 6 courses of chemotherapy, the primary lesion and multiple lymph node swellings greatly reduced in size and lymphangitis carcinomatosa improved. Accordingly, right colectomy with D3 nodal dissection was performed. The patient was recurrence free at her 8-month follow-up examination. Neoadjuvant chemotherapy with molecular targeted drugs is useful in the treatment of patients with unresectable primary cancer.
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PMID:[A case of advanced colon cancer successfully treated with combination therapy of cetuximab and oxaliplatin, leucovorin, and 5-fluorouracil]. 2439 80

A 71-year-old man presented with sigmoid colon cancer and multiple unresectable liver metastases. As the sigmoid colon cancer caused anemia, we performed laparoscopic-assisted sigmoidectomy prior to the administration of systemic chemotherapy. Bevacizumab (Bv) plus modified Leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) was administered as first line therapy.At 3 months from the start of chemotherapy, computed tomography revealed that the size of the liver metastases reduced by 49.45%, as evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). The only adverse event observed was Grade 1 peripheral neuropathy after the eighth dose of oxaliplatin.As the progression of peripheral neuropathy was observed at the ninth dose of oxaliplatin, oxaliplatin was omitted from further therapy; the patient was converted to maintenance therapy with simplified biweekly Leucovorin and fluorouracil (sLV5FU2). Bv plus mFOLFOX6 followed by sLV5FU2 for first-line therapy was effective for disease management over 23 months, but a partial response (PR) was the best overall response achieved.
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PMID:[A case of colon cancer with multiple liver metastases showing a long-term response following first-line therapy]. 2573 2


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