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)

We evaluated the effects of WR-2721 on the toxicity and antitumor activity of the combination of 5-fluorouracil (5FU) and carboplatin (CBDCA) in BALB/c and C57B1/6 mice. On a weekly schedule, i.p. injection of 200 mg/kg WR-2721 at 5 min prior to the administration of this combination enabled us to increase the CBDCA dose from a nontoxic level of 45 mg/kg to a normally toxic dose of 60 mg/kg in non-tumor-bearing BALB/c mice while maintaining the 5FU dose at 100 mg/kg. When WR-2721 was given 30 min before this combination, the CBDCA dose could not be increased to 60 mg/kg without producing drug-related deaths. WR-2721 protected against CBDCA- and 5-FU-induced thrombocytopenia but did not prevent leukopenia or anemia in C57B1/6 mice. The antitumor activity of the combination against colon 26 tumors in BALB/c mice was increased by pretreatment with WR-2721, which facilitated elevation of the CBDCA dose to 60 mg/kg in combination with 100 mg/kg 5FU. These results reveal better therapeutic efficacy for the combination of 5FU and CBDCA following pretreatment with WR-2721.
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PMID:Effect of WR-2721 on the toxicity and antitumor activity of the combination of carboplatin and 5-fluorouracil. 133 72

1. Pharmacodynamics and pharmacokinetics of antimetabolites. Antimetabolites are administered in the form of a base or its riboside, which is incorporated into the cell and converted to an active or inactive metabolite. The active metabolite remain in the cell inhibiting the enzymes to catalyze nucleotide synthesis for nucleotide triphosphate formation, but the inactive metabolites are rapidly excreted out of the cell. The inhibitory effect of antimetabolites on nucleotide formation is correlated with factors, such as maintenance of drug blood level, incorporation of the drug into the cell, activation and inactivation of the drug, affinity of the active form to the corresponding enzyme, and change in pool size of the intermediate metabolites in nucleotide synthesis. The salvage synthesis occurring at the higher level of the enzymes catalyzing nucleotide synthesis to counteract the inhibition by the drug is also correlated with the nucleotide formation. II. Pyrimidine antagonists 1. Cytosine arabinoside (ara-C) and its derivatives Ara-C is rapidly converted to ara-CTP and ara-U. The former remains in the cell and inhibits DNA polymerase, but the latter is excreted rapidly out of the cell. A small portion of ara-C is incorporated into DNA, which results in the degradation of DNA as demonstrated by reduced sedimentation of bulk DNA in alkaline sucrose gradient centrifugation and the ladder DNA fragmentation with a minimum fragment of approximately 180 base pairs and its conjugates in agarose gel electrophoresis. Behenoyl ara-C (BHAC) is highly lipophilic and highly distributed in the erythrocyte stroma and membrane fraction of leukocytes after iv infusion. The incorporated BHAC is released after the plasma BHAC level decreases, which suggests that erythrocytes can be a drug reservoir after iv infusion. Therefore, severe anemia should be treated before BHAC chemotherapy for longer maintenance of the plasma BHAC level. 2. 5-Fluorouracil (5-FU) and its derivatives Activation of 5-FU in the cells is metabolized by uracil metabolizing enzymes to FUMP and FdUMP. FUMP is further metabolized to FdUMP and is also incorporated to RNA. FdUMP produces a ternary complex with thymidylate synthetase and leucovorin; subsequently, conversion of dUMP to dTMP is strongly inhibited. Thus, FUMP and FdUMP inhibit RNA and DNA metabolism, respectively. Enzyme activity during 5-FU metabolism and consequently the degree of inhibition of DNA and RNA syntheses markedly differ with the tumor cell species. This should be taken into consideration when performing chemotherapy of malignancies.
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PMID:[Clinical pharmacology of anticancer agents (Part 4). Antimetabolites (1)]. 173 42

We describe a phase III trial on 200 patients with end stage squamous cell carcinoma of the head and neck. The patients were randomised to one of four treatment arms: cisplatinum alone, methotrexate alone, cisplatinum + 5-FU and cisplatinum + methotrexate. There was no significant difference in the response rates, but the survival of the cisplatinum arm was significantly better than that of the methotrexate arm. The survival of patients receiving cisplatinum as a single agent was longer than that of patients receiving cisplatinum in combination with methotrexate or 5-FU, but not significantly so. Nausea/vomiting and anaemia were significantly more common in the cisplatinum arms than in the methotrexate arm, but the toxicity of combination regimens was not significantly greater than that of cisplatinum used as a single agent.
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PMID:A phase III randomised trial of cistplatinum, methotrextate, cisplatinum + methotrexate and cisplatinum + 5-FU in end stage squamous carcinoma of the head and neck. Liverpool Head and Neck Oncology Group. 217 67

Anaemia was induced in rats with fluorouracil (5-FU) or cisplatin (CDDP) and the mechanisms of anaemia induction were analysed. Furthermore, the therapeutic effects of recombinant human erythropoietin (rHu Epo) on these anticancer drug-induced anaemias were investigated. In 5-FU-induced anaemia, marked serum erythropoietin (Epo) elevation was observed in inverse correlation to blood Hb concentration and Hb concentration rapidly recovered to normal levels. On the other hand, in CDDP-induced anaemia, serum Epo elevation was modest and the lowered Hb concentration persisted longer. Treatment with rHu Epo significantly improved both anticancer drug-induced anaemias but rHu Epo was more effective on CDDP-induced anaemia. These results suggest that rHu Epo might be useful for the therapy of anaemia associated with anticancer chemotherapy.
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PMID:Effect of recombinant human erythropoietin on anticancer drug-induced anaemia. 220 97

Thirteen patients with previously untreated advanced squamous cell carcinoma of the esophagus were treated with pre-radiation chemotherapy followed by radiation therapy. The chemotherapy consisted of two or three cycles of Cisplatin and 120 hour continuous infusion of 5-Fluorouracil. Three patients showed complete response (CR), three partial response (PR), three minor response (MR) and four non-response (NR). The overall response rate was 46%. The predominant side effects were nausea, vomiting and anorexia. Mild or moderate degree of anemia and leukocytopenia were also noticed. However, no serious toxicity was observed. Radiation therapy was administered to eleven of the thirteen patients, excluding one patient who refused it and one patient who died during chemotherapy. In two of the eleven cases, however, radiotherapy was discontinued because of MR, and surgery was performed. In one additional case, post-radiotherapy surgery was performed. One of these three cases received curative esophagectomy. After definitive treatment, CR was obtained in 54% (7 of 13), PR in 15% (2 of 13), MR in 15% and NR in 15%. The non-effective patients (PR + MR + NR) died within nine months after the initiation of treatment. Two of the CR patients later died, one due to local recurrence and another due to aortic-esophageal fistula with no residual cancer discovered at autopsy. The remaining CR patients are still alive and well, after 11.5 to 32 months. Although the follow-up period is yet short, the combination of radiation therapy with pre-radiotherapy chemotherapy appears to be an effective treatment.
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PMID:[Combined radiotherapy and pre-radiation chemotherapy with cisplatin and 5-fluorouracil for advanced esophageal carcinoma. II. Clinical evaluation in cases with higher than T2 stage]. 223 Apr 44

Previous clinical studies have suggested that 4'-O-tetrahydropyranyl-doxorubicin (THP) as well as 5-fluorouracil/high-dose folinic acid (5-FU/HDFA) are active and well-tolerated drugs in breast cancer treatment. This phase I-II study was designed to determine the maximum tolerated dose (MTD) of THP in combination with 5-FU/HDFA as a weekly schedule and to examine the activity and safety of this drug regimen in patients with advanced breast cancer. 5-FU and HDFA were set at doses of 350 mg/qm i.v. and 500 mg/qm i.v., respectively, whereas the THP dose has been escalated in increments of 5 mg/qm i.v. beginning at a dose level of 10 mg/qm until reaching of MTD in at least four patients in one dose level. For determination of MTD the first six cycles of each patient have been taken into account. Up to July 1990, 21 patients previously not treated with chemotherapy for metastatic breast cancer were entered into the study; the latest patient entered at 35 mg/qm THP dose level. A total of 270 cycles have been administered so far. Anemia and leukopenia was limited to ECOG grades I and II. Other toxicities were mild or moderate. No acute or subacute cardiotoxicity has been observed. Up to July 1990, MTD had not been reached. In the second part of the study, at least another 14 patients have to be entered in a dose level one below the MTD to evaluate the activity and safety of this regimen in a phase II trial.
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PMID:Combination therapy of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose folinic acid in patients with advanced breast cancer: a phase I-II study (preliminary results). 229 57

Twenty-eight patients with metastatic and/or recurrent non-small-cell lung cancer were treated with a new sequential combination of escalating doses of cisplatin (50, 75, and 100 mg/m2 IV X 1) followed by 5-FU infusion (40 mg/m2/hour X 72) and etoposide (80 mg/m2/day X 3). Three patients received concurrent external radiation therapy. Eleven of the 28 (39%) had a partial response to chemotherapy. Four others had a minor response. One partial responder became a complete responder by surgical excision of residual cancer. Median time to response was 6 weeks followed by a median response duration of 4 months. In responders, chemotherapy was discontinued at the time of maximal response. Median survival was 7 months. Chemotherapy was well tolerated with absence of leucopenia, thrombocytopenia, and nausea and vomiting in a majority of courses. The common toxicities were alopecia (100%), leucopenia (35%), nausea and vomiting (30%), and electrolyte imbalances (27%). Reversible nephrotoxicity, thrombocytopenia, anemia, mucositis, and diarrhea were infrequent. The response rate in stage IV was less than in stage III. The combination of moderate doses of cisplatin, 5-FU infusion, and etoposide provides a new palliative chemotherapy that is well tolerated with concurrent/sequential radiation therapy and may be useful in the multimodality treatment of non-small-cell lung cancer.
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PMID:Toxicity of FED chemotherapy in non-small-cell lung cancer. 244 89

Cis-platinum, 5-fluorouracil and bleomycin are active agents in head and neck SCC. When given by continuous infusion (C.I.) lower toxicity and increased activity have been reported. A 4-day trial of triple C.I. including these reagents was conducted for recurrent and/or metastatic head and neck SCC. Cis-platinum 25 mg/m2/day, 5-FU 650 mg/m2/day and bleomycin 10 mg/m2/day were given for 4 days every 4 weeks. Twenty-nine patients were entered, 27 were evaluable for toxicity and 3 for response. The response rate was 30% (one CR and seven PR). Patient compliance was poor (one central and one peripheral i.v. line) and toxicity was acceptable except for the unexpected anemia; 48% of patients required red cell transfusion. One patient died of bleomycin-induced lung toxicity and minor renal toxicity related to parenteral hydration was observed in the first 16 patients. In conclusion, this combination is moderately active in recurrent and/or metastatic head and neck SCC. Patient compliance was poor and cumulative anemia was an unexpected toxic event. Further trials with this triple C.I. chemotherapy are not recommended for the alcoholic, undernourished, very advanced cancer patient population.
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PMID:96-hour continuous infusion of cis-platinum, 5-fluorouracil and bleomycin in recurrent or metastatic head and neck squamous cell carcinoma, unexpected anemia. 248 Feb 45

The epidemiology, histopathology, diagnosis and staging, and treatment of prostate cancer are reviewed. Prostate cancer, one of the most common malignancies occurring in men over age 50, will strike an estimated 103,000 men in the United States in 1989. More than 95% of prostatic tumors are adenocarcinomas. Tumors are graded on the basis of their degree of differentiation. Most afflicted men initially complain of difficulty in starting the urinary stream and of urinary bleeding, dribbling, and retention. Urinary obstruction may be present in advanced disease, and anemia, anorexia, and bone pain are common in metastatic disease. Prostatectomy and irradiation are used to treat disease localized to the prostate; the prognosis for such patients is good. Survival is diminished in cases of locally advanced and metastatic disease. Symptomatic metastatic disease is treated by hormonal manipulation through orchiectomy and administration of exogenous estrogens (diethylstilbestrol), luteinizing hormone-releasing hormone analogs (leuprolide and goserelin), and antiandrogens (cyproterone acetate, flutamide, and others). Some 70-80% of patients respond to hormonal therapy for periods of up to three years. After relapse occurs, salvage hormonal therapies (aminoglutethimide and ketoconazole) may be attempted to prolong survival. Fluorouracil, doxorubicin, mitomycin, cisplatin, cyclophosphamide, methotrexate, and estramustine have also been administered, with mixed results. Once relapse occurs in prostate cancer patients after initial hormonal therapy, the response to salvage hormonal or cytotoxic therapy is minimal; in the future, total androgen blockade and methods of decreasing drug resistance may be used to prolong survival.
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PMID:Treatment of prostate cancer. 266 30

A 59-year-old male undergoing an exploratory laparotomy for stage IV gastric cancer (H0P1N4S3) was treated concomitantly with Lentinan, 5-FU and MMC. The CEA values, fluoroscopic and endoscopic findings and histology by biopsy were investigated sequentially. Three months after the beginning of treatment, clinical symptoms had nearly disappeared. Body weight increase and recovery from anemia were observed. The CEA value which had shown a high preoperative level of 114.2 ng/ml decreased to 4.0 ng/ml. The marked improvement of endoscopic findings and no cancer cells were seen in several biopsy specimens. However, the condition of the patient deteriorated six months later. This patient showed clear improvement, although temporary, with immunochemotherapy.
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PMID:[A gastric cancer showing marked improvement (stage IV) with lentinan immunotherapy and 5-FU, MMC-chemotherapy]. 283 2


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