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)

The results of a phase I--II study of a combination chemotherapy with AAFC and ICRF-159 in advanced adenocarcinoma of digestive origin are presented. Myelosuppression was the dose-limiting toxicity with anemia, leukopenia, and thrombocytopenia. The maximum tolerated dose of AAFC in the combination program was 650 mg/m2 I.V. weekly. ICRF-159 was given in a 3-day course every 3 weeks and the dose was escalated from 125 mg/m2 to 500 mg/m2 daily. Bone marrow toxicity was noticied at the first escalation level and all dose levels were similarly toxic. The results of this combination chemotherapy were: two partial responses in 14 patients with gastric cancer; no responses in nine patients with colorectal cancer; no responses in three patients with pancreatic cancer; and no responses in two patients with biliary tree cancer. In conclusion, AAFC and ICRF-159 combination chemotherapy demonstrated a low level of activity in advanced carcinoma of digestive origin. The peculiar hematologic toxicity found at the low-level dose requires further documentation and could make this drug association suitable for a phase II study in leukemia and/or lymphoma.
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PMID:Phase I and II clinical study of anhydro-ara-5-fluorocytosine (AAFC) and ICRF-159 combination in adenocarcinoma of digestive origin. 9 30

Eleven patients with myeloid blast cell crisis and two patients with lymphoid blast cell crisis of chronic myeloid leukemia were treated with ICRF-159. Two of the patients with myeloid blast cell crisis achieved partial bone marrow remission and survived for 8+ and 18 months. One of the patients with lymphoid blast cell crisis reverted to the chronic phase of chronic myeloid leukemia after therapy with ICRF-159 in combination with prednisolone. The only significant toxic effect was myelosuppression.
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PMID:Treatment of blast cell crisis of chronic myeloid leukemia with ICRF-159 (razoxane). 29 8

Twenty-eight patients with advanced acute nonlymphocytic leukemia, 16 with acute lymphoblastic leukemia, and two with acute undifferentiated leukemia were treated with ICRF-159. No patient achieved a complete remission and only three patients (6%) achieved a partial bone marrow remission. The only significant toxic effect was myelosuppression which probably contributed to the death of six patients. Five patients with acute nonlymphocytic leukemia and one with acute lymphoblastic leukemia received a combination of ICRF-159 and low-dose cytosine arabinoside. There were no remissions in this group and the toxic effects were more marked than with ICRF-159 alone. This study confirms the limited activity of ICRF-159 as a single agent in acute leukemia demonstrated in smaller series, and shows that, when used in combination with low-dose cytosine arabinoside, it was ineffective and resulted in increased toxicity. ICRF-159 alone or in combination with cytosine arabinoside has very limited activity in advanced adult acute leukemia.
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PMID:Limited activity of ICRF-159 in advanced acute leukemia. 36 84

Early phase II study of MST-16[4,4-(1,2-ethanediyl) bis (1-isobutoxycarbonyloxy-methyl-2, 6-piperazinedione], a derivative of ICRF-154, on malignant lymphoma was conducted by multi-institutional cooperative group. MST-16 was administered orally at doses of 1,600 mg/body/day for 5 days or 1,200 mg/body/day for 10-14 days, mainly. The number of registered and evaluated patients were 29 and 28, respectively (Hodgkin's disease 3 patients and non-Hodgkin lymphoma 25). Twenty-seven of 28 patients had received prior chemotherapy and/or radiation therapy. Of 28 evaluable patients, overall response rate (CR + PR) was 32.1%. In high-dose administration group, the response rate was not significantly high. The response rate seemed to be high in patients who were treated repeatedly (number of courses greater than 3). Major side effects observed were myelosuppression and gastro-intestinal disorders which were reversible in a rest period. Myelosuppression seemed to be severe in high-dose administration group. This study indicated that MST-16 was a useful agent against malignant lymphoma including primary resistant or relapsed patients, and that the recommended regimen for a late phase II study was considered to be 1,600-2,400 mg/body/day for 5-7 days repeatedly with a pause of several days. Furthermore, the study should be considered at the dose of 3,200 mg/body because half cases administered at this dose showed some response.
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PMID:[Early phase II study of MST-16 (sobuzoxane) on malignant lymphoma]. 195 63

ICRF-187, the enantiomer of ICRF-159 formulated for iv use, was administered to 23 patients in a phase I clinical trial. The dose ranged from 500 to 1500 mg/m2 every day for 3 days and was repeated every 28 days. The toxic effects included moderate to severe leukopenia and thrombocytopenia, which recovered by the 21st day of a treatment cycle. Myelosuppression was more severe in patients with prior nitrosourea treatment. Nonmyelosuppressive toxic effects included nausea and vomiting, transient elevations in liver function tests, alopecia, and increased urinary clearances of iron and zinc. The starting dose for phase II trials should be 1250 mg/m2 daily for 3 days repeated at 21-day intervals.
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PMID:Phase I study of ICRF-187 using a daily for 3 days schedule. 678 38

ICRF-159 is a bis-diketopiperazine derivative active in a variety of preclinical animal tumor models. Because of its poor solubility characteristics, the drug must be given p.o. However, when given by this route at high doses, poor bioavailability was noted. Two interesting preclinical properties of this agent are its antimetastatic effect and the ability to reduce anthracycline cardiotoxicity. Phase I studies have delineated myelosuppression as the major toxicity with GI toxicity also occurring. In phase II studies, interesting activity has been noted in lymphomas and head and neck carcinomas. When ICRF-159 was combined with radiotherapy, prolonged responses were noted in sarcoma and lung carcinoma in small numbers of patients. Further studies are indicated in areas of activity as a single agent and as a potentiator of radiation therapy.
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PMID:Bis-diketopiperazine derivatives in clinical oncology: ICRF-159. 700 Mar 89

A clinical trial of ICRF-159 was done in patients with Hodgkin's disease and non-Hodgkin's lymphomas whose tumors had become resistant to conventional chemotherapy. Antitumor effect and toxicity were compared in patients who were randomly assigned to receive either a loading course or a weekly regimen. Among 82 evaluable cases, five of 39 (13%) treated with the loading course schedule and six of 43 (14%) treated with the weekly schedule experienced objective tumor regressions. Response duration tended to be brief (median, 7 weeks). Life-threatening myelosuppression was more frequent in patients receiving the loading course regimen. Survival was somewhat longer among patients receiving the weekly schedule (median survival, 24 versus 12 weeks; P = 0.04). ICRF-159 demonstrated definite but limited therapeutic activity in this population of patients with advanced malignant lymphomas. The weekly schedule was associated with fewer episodes of life-threatening toxicity and longer patient survival.
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PMID:Randomized clinical trial comparing two dose regimens of ICRF-159 in refractory malignant lymphomas. 700 38

This report summarizes the results of a randomized multi-institutional clinical trial in advanced gastric carcinoma comparing four combination chemotherapy regimens: 5-FU, Adriamycin + mitomycin C (FAMi); 5-FU, Adriamycin + methyl-CCNU (FAMe); 6-FU, ICRF-159 + methyl-CCNU (FIMe); and 5-FU + methyl-CCNU (FMe). One-hundred-eight-one evaluable patients received chemotherapy. These objective tumor response rates were observed among the 59 patients with measurable indicator lesions: FAMi, 3/12 (25%); FAMe3, 3/10 (30%); FIMe, 4/19 (21%); FMe, 1/18 (6%). The survival distributions for the four treatment groups were significantly different (P less than or equal to 0.05), with these median survivals observed (in weeks from the onset of chemotherapy): FAMi, 29.6; FAMe, 34.4; FMe, 22.9; FIMe, 17.4. Two nontreatment variables were found to be significantly associated with survival when analyzed using the Cox covariate model: pretreatment performance status (P less than 0.0001), and presence or absence of measurable metastatic disease (P less than 0.001). After adjustment for the effects of these and other clinical variables, two treatment regimens were found to be associated with improved survival: FAMi therapy (P less than 0.01), and FAMe therapy (P = 0.07). Toxicity was, in general, moderate and consisted primarily of gastrointestinal side effects and myelosuppression. We conclude that the FAMi and FAMe regimens are superior to the FIMe and FMe regimens in the management of advanced gastric cancer.
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PMID:A comparative clinical assessment of combination chemotherapy in the management of advanced gastric carcinoma: The Gastrointestinal Tumor study Group. 703 63

ICRF-159, and EDTA derivative antitumor agent, was given to 21 patients with advanced gastric cancer in a weekly dose of 3000 mg/m2. Of the 21 patients, 11 had failed prior drug therapies and 10 were previously untreated. No patient achieved an objective partial response (actual response less than 15% with 95% confidence level). One previously treated patient had a minor response lasting 12 weeks and four patients (three previously untreated) had stable disease lasting 4-8 weeks. Toxicity was acceptable, consisting of mild nausea and moderate myelosuppression. Median survival after treatment was 17.5 weeks in previously untreated patients and 9 weeks in previously treated patients. We conclude that ICRF-159 is inactive in advanced gastric cancer when given on a weekly schedule.
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PMID:ICRF-159 in advanced gastric cancer. Absence of activity. 716 6

Twenty-four patients with advanced metastatic colorectal cancer with measurable sites of disease were treated with a combination of 5-FU, methyl-CCNU, ICRF-159, and triazinate. Only two had objective regression of disease. Two patients died of complications from drug-induced myelosuppression. Toxic effects were moderate in the remaining patients. Attempts to escalate doses were limited by myelosuppression. The regimen used has no advantage over 5-FU alone. It is unlikely that triazinate and ICRF-159 will add substantially to the efficacy of chemotherapy for colorectal cancer.
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PMID:Combination chemotherapy for advanced colorectal cancer with triazinate, ICRF-159, 5-FU, and methyl-CCNU. 745 2


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