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)

101 patients with acute leukemia in relapse were treated with 5-azacytidine according to three schedules: Regimen A--300 mg/m2(day divided intravenously at 8 hour intervals for 5 days; Regimen B--750 mg/m2 as a single iv pulse dose administered at 2 to 3 weeks intervals; and Regimen C--300 mg/m2/day by continuous infusion daily for 5 days. Twelve patients achieved a complete remission (CR) and six achieved a partial remission (PR) for an overall 18% response rate. Of 78 patients receiving an adequate trial the response rate was 23%. An average of 1.5 courses and a median of 5 weeks were necessary to achieve a response. The median duration of CR patients was 21 weeks and for PR patients it was 5 weeks. Response rates were 24% for Regimen A, 0 for Regimen B, and 1 of 8 for Regimen C. The CR rate for AML and AMML was 13%. Two of eight AMoL patients achieved a CR. Only 2 of 23 ALL patients responded, one of whom achieved a CR. Toxicity included moderate to severe nausea and vomiting, diarrhea, stomatitis, skin rash, and prolonged myelosuppression. 5-azacytidine has significant activity in the acute nonlymphoblastic leukemias.
Cancer 1978 Nov
PMID:5-azacytidine in acute leukemia. 8 72

Nine patients with advanced cancer of the uterine cervix, having failed radiotherapy, were treated with a combination regimen of parenteral methotrexate, bleomycin, and cis-dichlorodiammineplatinum(II). Eight of the patients had objective partial remissions lasting a median of 4 months. All patients improved subjectively. Five of the patients, however, had sudden unpredictable onset of severe myelosuppression accompanied by stomatitis. Such frequent severe toxicity was not observed in patients with other malignancies treated with this combination. It is likely that impaired excretion of methotrexate resulting from ureteral dysfunction led to increased toxicity. In future protocols for advanced cervical cancer, methotrexate will be replaced by other effective agents. The very high response rate (89%) suggests that similar but less toxic combinations may contribute substantially to the future effective treatment of advanced cervical cancer.
Cancer Treat Rep 1979 Jun
PMID:Chemotherapy for advanced cervical cancer with methotrexate, bleomycin, and cis-dichlorodiammineplatinum(II). 8 7

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.
Cancer Clin Trials 1978
PMID:Phase I and II clinical study of anhydro-ara-5-fluorocytosine (AAFC) and ICRF-159 combination in adenocarcinoma of digestive origin. 9 30

A prospective randomized trial was conducted comparing the addition of iv hyperalimentation (IVH) to Corynebacterium parvum, isophosphamide, and adriamycin (CIA) chemoimmunotherapy in 26 patients with extensive squamous cell lung cancer. Thirteen patients were entered in each treatment arm of the study and IVH was administered before and after the first course of CIA for a total of 31 days. The major dose-limiting toxic effect of CIA was leukopenia. Less myelosuppression was observed for the patients receiving IVH. The difference in the lowest recorded leukocyte and neutrophil counts between the two groups was significant (P = 0.03 and 0.01, respectively). Also, a significant decrease (P = 0.06) in nausea and vomiting associated with chemotherapy administration was found for the IVH gorup. The differences in toxic effects between each group were not maintained over subsequent courses of therapy when both groups received CIA alone. The prevention of the toxic effects of chemotherapy by IVH suggests a means of giving higher chemotherapy doses with the intent of increasing tumor response and patient survival.
Cancer Treat Rep 1978 Aug
PMID:Protection against chemotherapy toxicity by IV hyperalimentation. 9 35

Thirty-four patients resistant to cyclophosphamide and Adriamycin received hexamethylmelamine at one of two dose regimens: 6 mg/kg/day orally for 21 days every 4 weeks or 8 mg/kg/day orally for 21 days every 6 weeks. Only five patients responded. Tolerance to the drug was, however, satisfactory; nausea, pyrosis, and vomiting were the only frequent side effects. Myelosuppression occurred in only one case.
Cancer Treat Rep 1979 Aug
PMID:Hexamethylmelamine in ovarian cancer resistant to cyclophosphamide and adriamycin. 11 96

A phase II trial of pyrazofurin, alone and in combination with trifluorothymidine, was carried out in patients with advanced non-Hodgkin's lymphoma. None of the 19 patients evaluable for response had complete or partial remissions but 14 had minor regressions. Toxicity, consisting primarily of myelosuppression and stomatitis, was of moderate severity. These studies suggest that pyrazofurin, alone or in combination with trifluorothymidine, is of limited utility in advanced non-Hodgkin's lymphoma.
Cancer Treat Rep 1979 Aug
PMID:Phase II trial of pyrazofurin, alone and in combination with trifluorothymidine, in non-Hodgkin's lymphoma. 11 97

Structure-activity studies of nitrosourea pharmacology have resulted in the synthesis of a new water-soluble agent,chlorozotocin, which has significant antitumor activity against the L1210 leukemia system and produces only a minor degree of inhibition of mouse and human bone marrow DNA synthesis compared to BCNU. It is important to emphasize that the bone marrow sparing feature of chlorozotocin is relative and that if the drug is administered at lethal dose levels in mice, myelosuppression is observed. The potential importance of these studies is the identification of a new and active nitrosourea antiumor agent with modified bone marrow toxicity. If aminoglucose modification of nitrosourea bone marrow toxicity can be confirmed in man without significant loss of antitumor activity, the use of such a compound could facilitate treatment of patients with neoplastic disease who have pre-existing abnormal bone marrow function. It would also allow the more effective use of a nitrosourea agent in combination with anticancer agents possessing more potent myelosuppressive properties.
Cancer Treat Rep 1976 Jun
PMID:Pharmacology of chlorozotocin Nsc-178248), a new nitrosourea antitumor agent. 13 56

1-(2-Chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), a water-soluble nitrosourea, differs from 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) by the placement of the cytotoxic group on C-1 of glucose. Its biological and biochemical properties are compared with those of chlorozotocin. At a 10% lethal dose (10 mg/kg i.p.), GANU demonstrates minimal myelosuppression. This dose failed to depress normal bone marrow DNA synthesis, in contrast to a 96% inhibition in L1210 DNA synthesis. In L1210 cell suspension, equimolar doses of GANU and chlorozotocin produced equivalent degrees of inhibition in DNA synthesis. GANU has significant L1210 activity in BALB/c X DBA/2 F1 mice treated on Day 2 of tumor growth. A 117% increased life-span and 15% 45-day survivors are atained with 15 mg/kg i.p., a 50% lethal dose. However, in concurrent studies using randomly selected littermate groups of mice, GANU proved less active than chlorozotocin which produced a 306% increased life-span (15 mg/kg i.p.). GANU and chlorozotocin have similar in vitro alkylating activity but the in vitro carbamoylating activity of GANU is sevenfold that of chlorozotocin. On a molar basis, the lethal toxicity of GANU is twice that of chlorozotocin. The significant carbamoylating activity of GANU may contribute to its greater toxicity and therefore limit the mumoles of alkylating agent that can be administered to the tumor. These structure-activity studies further confirm that the addition of a glucose carrier to a cytotoxic nitrosourea moiety can selectively reduce bone marrow toxicity while retaining antitumor activity.
Cancer Res 1977 Mar
PMID:Biological and biochemical properties of 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (NSC D 254157), a nitrosourea with reduced bone marrow toxicity. 13 78

One hundred thirty-eight adults with advanced cancers were treated with Baker's Antifol. The complete response + partial response rate was only 10%. Best responses were obtained in 31 patients with lung adenocarcinoma (complete response + partial response, 13%), in 25 patients with colorectal carcinoma (partial response, 16%), and in 6 patients with renal cell carcinoma (partial response, 50%). Two partial responses occurred in 15 patients with squamous cancer. No significant responses were seen in 27 patients with other adenocarcinomas, 13 with sarcomas, 14 with melanomas, and 8 with miscellaneous tumors. The most frequent toxicities were dermatitis, stomatitis, gastrointestinal symptoms, and mild myelosuppression. The incidence of dermatitis was significantly decreased by shortening the schedule of Baker's Antifol administration from 5 to 3 days. Baker's Antifol has some degree of antitumor activity, and studies of combination of this agent with other effective chemotherapeutic agents are indicated.
Cancer Res 1977 Apr
PMID:Phase 2 study with Baker's Antifol in solid tumors. 13 5

Eighty one patients (59 females, 22 males) with advanced solid tumors were treated with Adriamycin in doses of 40 mg/m2 body surgace daily, in two days cycles, with resting periods of 3 weeks. Overall response rate was 46% (37/81). In breast cancer response rate was 56% (13/23) and in ovarian cancer 48% (13/27). In various other tumors remission was observed in soft tissue sarcomas (3/8), thyroid cancer (1/7), osteogenic sarcoma (1/4), oesophageal cancer (2/4), lung cancer (2/4), bladder cancer (1/2) and hepatoma (1/2). In breast cancer patients, 2-7 month remission duration was observed (M equal to 4.5 month) and in ovarian cancer 1.5-5 month (M equal to 3.2 month). Adriamycin was also applied intrapleurally in 31 patients with malignant pleural effusions with a low response rate (26%). This modified schedule of Adriamycin administration showed a high antitumor activity in breast and ovarian cancer and in soft tissue sarcomas. Squamous cell carcinoma of the esophagus was also sensitive to Adriamycin therapy. The very low rate of myelosuppression and oral ulceration showed the decreased toxicity of this Adriamycin administration schedule.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977
PMID:Modified administration schedule of adriamycin in solid tumors. 14 May 42


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