Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-two patients with advanced solid tumors were treated with a quinazoline folate antagonist, trimetrexate, to determine the toxicity spectrum, the maximal tolerated dose, and the pharmacokinetics of the drug. Negligible toxicity was seen with single doses of 10-70 mg/m2 given as a 1-h infusion. Single doses of 120 mg/m2 infused over 1 h caused moderate to grade 4 toxicity in five of nine patients treated. Two patients who had no toxicity at this level were escalated to a dose of 213 mg/m2 with mild to moderate toxicity. The primary dose-limiting toxicity was myelosuppression. Moderate transaminase elevations, rash, anorexia, nausea and vomiting, and mucositis were occasionally seen. Although there was variation in dose tolerance to this drug, with selected patients able to tolerate higher doses, we consider 120 mg/m2 every 2 weeks to be the maximal tolerated dose, and the recommended Phase II starting dose. Trimetrexate plasma concentration-time curves were best described as biphasic (N = 9) or triphasic (N = 5) in form. The half-life of the terminal elimination-phase was 16.4 h. The mean residence time was 17.8 h. The volume of distribution of the plasma compartment and the volume of distribution at steady-state were 0.17 and 0.62 liter/kg, respectively. Plasma clearance was 53 ml/min. Plasma concentrations as determined by dihydrofolate reductase enzyme inhibition assay and high-performance liquid chromatography were initially identical, but diverged at later times. Divergences were seen also in urinary recovery as determined by the two methods. Both results suggest the appearance of metabolite(s) of trimetrexate which can inhibit dihydrofolate reductase. Measurable objective solid tumor responses were not seen in this Phase I study, although three patients with colon cancer had stable disease lasting 18, 26, and 26 weeks, respectively.
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PMID:Phase I studies with trimetrexate: clinical pharmacology, analytical methodology, and pharmacokinetics. 294 79

Thirty-nine patients with small cell carcinoma of the lung were treated sequentially with induction chemotherapy, radiotherapy and then maintenance chemotherapy. Induction chemotherapy consisted of two regimens, cyclophosphamide, vincristine, methotrexate (COM) and adriamycin, ACNU, vindecine (ANV) given by randomization. Radiotherapy was given for patients with limited disease (LD) as a rule. After radiotherapy the drugs used for maintenance chemotherapy were alternated and reduced in dose. Eighteen patients were treated with a COM-ANV sequential combination and sixteen patients were treated with an ANV-COM combination. Thirteen patients had limited disease (LD) and eleven patients had extensive disease (ED). Of 12 patients with LD treated with COM-ANV therapy, 9 patients (75%) responded with 3 (25%) complete responses. Of 11 patients with LD treated with ANV-COM therapy, 9 patients (81.8%) responded to the therapy. According to disease extent, response rate was 82.6% for LD and 54.5% for ED. The median survival times were 9 months for patients with COM-ANV therapy and 12 months for those with ANV-COM therapy. Also, the median survival time was 15 months for LD patients and 5 months for ED patients. Major toxicities in ANV therapy were anorexia, nausea, and myelosuppression, and were more frequent than with COM therapy. These results showed no clear evidence of superiority in either the COM-AMV or ANV-COM regimen.
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PMID:[Combination chemotherapy and radiotherapy in small cell carcinoma of the lung]. 301 41

Twenty previously treated patients with advanced bone sarcomas received thrice weekly im 50 X 10(6) IU/m2 doses of human alfa-interferon (interferon alfa-2a, recombinant; Roche). Seventeen patients had metastatic osteosarcomas and one each had fibrosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma. Two patients with osteosarcoma and the one with malignant fibrous histiocytoma experienced objective partial tumor regression for 1, 3, and 2 months, respectively. Fever, anorexia, myalgia, fatigue, lethargy, and moderate myelosuppression were observed commonly, and some patients developed mild nausea, vomiting, and diarrhea. No patient withdrew because of toxicity and no dose reductions were necessary except adjustments for changes in body surface area secondary to weight loss.
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PMID:Phase II study of recombinant alfa-2a interferon in patients with advanced bone sarcomas. 303 15

Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the deoxyribonucleic acid of dividing cells in a competitive process with thymidine; BUdR also sensitizes these cells to radiation therapy. Neurons and glial cells have a very low mitotic rate. They will not incorporate BUdR and will not be sensitized. Bromodeoxyuridine is best delivered intra-arterially because of its regional advantage, calculated to be between 6 and 16. An 8-week BUdR infusion is delivered before and during radiation therapy through a permanently implanted pump with a catheter placed retrograde into the external carotid artery. Eighteen patients with malignant glioma (15 grade IV, and three grade III) were entered into a Phase I dose-escalation protocol with BUdR dosages ranging from 400 to 600 mg/sq m/day. The maximum dose that can be tolerated appears to be 400 mg/sq m/day for 8 weeks. The 18 patients entered in this study have a median Kaplan-Meier estimated survival time (+/- standard error of the mean) of 22 +/- 5 months with 11 patients still alive. Three patients are alive at 30, 29, and 21 months after diagnosis with no evidence of tumor on computerized tomography. There have been no vascular complications. Side effects in all patients have included anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, iritis, and nail ridging. Myelosuppression requiring dose reduction occurred in one patient. One patient had a Stevens-Johnson syndrome requiring termination of BUdR. It is concluded that intra-arterial BUdR may improve survival times in patients with malignant gliomas.
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PMID:Intra-arterial bromodeoxyuridine radiosensitization and radiation in treatment of malignant astrocytomas. 304 41

A phase II study of UFT (a mixture of uracil and tegafur; molar ratio of uracil to tegafur = 4) was undertaken in 21 patients with advanced non-small cell lung cancer (NSCLC). UFT was administered orally at a dose of 400 mg/m2 every day, for more than four weeks. Of 16 adequately treated patients, one (6.3%) showed a partial response. Toxic effects included minimal myelosuppression, anorexia, nausea, vomiting and epigastralgia. Gastrointestinal toxicity was well tolerated. Considering the poor response and mild toxicity, a further phase II study of higher-dose UFT is necessary for patients without prior therapy.
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PMID:Phase II study of UFT in patients with advanced non-small cell lung cancer. 309 Mar 13

Twenty-seven patients with assessable, regionally advanced, or metastatic upper aerodigestive cancer of diverse histology received a combination of mitomycin C, adriamycin, and cis-diamminedichloroplatinum. All patients had previously received extensive surgery and/or radiation therapy. We observed an overall 46% partial response rate (12/26). This included seven of 15 (47%) responders with squamous cell carcinoma. Six of those seven patients responded within the initial month of treatment. For all study participants, the median time to progression and survival was 3.8 months and 7.3 months, respectively. Moderate-to-severe nausea, vomiting, anorexia, and alopecia were the most common toxicities. Myelosuppression (WBC less than 4,100 cells/mm3) and thrombocytopenia (PLTS less than 130,000 cells/mm3) occurred in 100% and 71% of the 21 patients with nadir data recorded, respectively. There were no episodes of sepsis nor did we detect any meaningful impairment in renal function. This regimen is active in the previously treated head and neck cancer patient and can be conveniently administered on an outpatient basis with acceptable and manageable side effects.
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PMID:A phase II clinical trial of the combination mitomycin C, adriamycin, and cis-diamminedichloroplatinum in patients with advanced upper aerodigestive cancer. 309 35

A phase II clinical trial on MDS was conducted in a cooperative study with orally administrable ara-C analogue, PLAC, which is resistant to cytidine deaminase and had shown an anti-tumor activity on various experimental tumors by oral route. Fifty MDS (3 RA, 18 RAEB, 11 RAEB-T, 18 RAEB-blast crisis (BC) were treated orally with 100 to 400mg/body of daily PLAC. One good response (GR) and 3 partial responses (PR) were obtained in 18 RAEB, and 2 complete remissions, 1 GR and 1 PR were noted in 11 RAEB-T, while 3 PR were seen in 18 RAEB-BC. Overall CR rates were 4%, GR rates 4% and PR rates 14%. Thus, 22% of MDS responded to oral PLAC. No clear daily dose-response was noted. Response, however, was dependent on the treatment period and was obtained in cases which had been treated for more than 20 days. Besides myelosuppression, side effects were mainly gastrointestinal, and anorexia (32%), nausea/vomiting (30%) and diarrhea (8%) were observed. Oral PLAC seems to be active on MDS which does not necessarily require admission to hospital.
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PMID:[Treatment of myelodysplastic syndromes (MDS) with oral administration of N4-palmitoyl-1-beta-D-arabinofuranosyl cytosine (PLAC)]. 338 95

A phase II study of a new anthracycline anti-cancer antibiotics, epirubicin (EPI), was undertaken in 71 patients with urothelial malignancies; 40 with advanced urothelial malignancies and 31 with superficial bladder cancer. Out of them 32 patients with advanced stage of urothelial cancer were evaluated for the systemic use of EPI, while 30 patients with superficial bladder cancer for intravesical use. Intravenous administration of this new anticancer antibiotic, at a dosage of 60 mg/m2 every three weeks, showed the response rate of 20.0% for advanced bladder cancer and 14.3% for renal pelvic and ureteral tumors. In cases of superficial bladder cancer, at a dosage of 60 mg/30 ml X 3 day every week in principal, the response rate was 66.7%. Eight out of 30 patients showed complete disappearance of the tumor. Twelve patients also showed more than 50% tumor regression. As for adverse effects no serious cardiotoxicity was demonstrated. Anorexia and other gastrointestinal side effects, such as nausea and vomiting, were also seen. Alopecia and myelosuppression were the major adverse effects among patients with systemic EPI administration. With intravesical use of EPI, cystitis syndrome was the major toxicity. However, no systemic side effects were noted in these cases. In conclusion, EPI was assumed to be effective for the treatment of advanced urothelial tumors and superficial bladder cancer.
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PMID:[Cooperative phase II study of epirubicin (EPI) in bladder cancer, renal pelvic and ureteral tumors--Urological Cooperative Study Group of EPI]. 346 92

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13-34 mg/m2 for 3-5 consecutive days or 35-50 mg/m2 at 3-4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.
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PMID:A phase II study of (2"R)-4'-0-tetrahydropyranyladriamycin (THP) in hematological malignancies. 366 66

A phase I study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg-1 which was escalated up to 24 mg kg-1 according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg-1 which was escalated up to 24 mg kg-1. Major side effects were nausea, vomiting and anorexia, and mild myelosuppression was noted at 12 mg kg-1 or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg-1 or more and became frequent at 7 mg kg-1 or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg-1 or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg-1 day-1 of PLAC.
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PMID:Phase I clinical and pharmacokinetic study of orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine. 366 79


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