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)

A phase I study of single i.v. doses of a new sugar containing nitrosourea 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809, EDMN) has been carried out in 47 patients with advanced solid tumors. Nine dose levels between 200 and 4500 mg/m2 were examined. Nausea and vomiting were seen in most patients but were controlled with antiemetics. Myelosuppression was minimal. The dose-limiting toxicity was hepatotoxicity, occurring early (peak at days 2-4) and resolving rapidly. No cumulative toxicity was seen with an every 6 weeks schedule. Other toxicities were abdominal pain, diarrhea, arm pain, restlessness, and headache. Pharmacokinetic studies in 20 patients using an HPLC assay and in 5 patients using [14C]EDMN showed a short half-life, rapid plasma clearance, rapid metabolism, and minimal excretion of unchanged drug. There was one partial response in a patient with colon carcinoma. The recommended dose for phase II studies in 3750 mg/m2 every 6 weeks.
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PMID:Phase I clinical trial of ethyl 6-deoxy-3,5-di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809). 330 87

Hexamethylene bisacetamide (HMBA, NSC 95580) has been demonstrated to be the most effective of the known and studied polar-planar compounds at inducing differentiation in a wide variety of leukemic and nonleukemic cell lines. Although HMBA demonstrated no antineoplastic activity in preclinical testing, it was selected for clinical development on the basis of its potent differentiating capabilities in vitro. In this phase I study, HMBA was administered as a continuous five-day infusion every 3 weeks to patients with advanced cancer. Twenty-three patients received 35 evaluable courses at doses that ranged from 4.8 to 33.6 g/m2/d. Dose-limiting toxicities included renal insufficiency, a hyperchloremic metabolic acidemia/acidosis, and CNS toxicities manifested by agitation and delirium, which progressed to coma in one patient who developed concomitant renal insufficiency. Moderate myelosuppression, mucositis, nausea, and vomiting were also observed. The pharmacokinetics of HMBA best fit a single compartmental model and disposition is primarily by renal elimination. Renal excretion of HMBA and of the primary metabolite, 6-acetoamidohexanoic acid, together account for the disposition of 66% to 93% (mean, 74%) of the infused drug. Based on this trial, the maximum tolerated and recommended phase II doses for HMBA administered on this schedule are 33.6 and 24 g/m2/d, respectively. However, since steady-state HMBA levels at these doses were in the range of 1 to 2 mmol/L, only approaching the lower limit demonstrated for in vitro differentiating effectiveness, and because of evidence suggesting that the exposure period is an important variable in the induction of differentiation, additional studies examining longer periods of infusion are warranted.
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PMID:Phase I and pharmacologic study of hexamethylene bisacetamide in patients with advanced cancer. 378 6

SK&F107647 is a synthetic hematoregulatory peptide (HP) increases both the number and function of progenitor cells, enabling improved survival after lethal myelosuppression, lethal fungal infection, and lethal herpes simplex virus infection in murine models. This Phase I single-blind placebo-controlled dose-rising crossover trial examined the efficacy of SK&F107647 in patients who had incurable solid tumor malignancies. Sixteen patients were treated. Six adverse events in 3 patients were considered to be possibly related to SK& F107647; all were mild to moderate in nature (mild nervousness and agitation at 0.01 ng/kg, moderate fever and mild nausea at 0.1 ng/kg, elevated hepatic enzymes at 0.1 ng/kg, and mild vomiting at 1.0 ng/kg). Plasma half-life was 2.44 hours (+/-1.07 standard deviation). The observed area volume of distribution was 16.7 L (+/-7.7 standard deviation) and clearance was 5.04 L/hour (+/-1.83 standard deviation). When administered as a single 2-hour intravenous infusion at doses ranging from 0.01 to 100 ng/kg, SK&F107647 is safe and well tolerated.
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PMID:SK&F107647: a synthetic hematoregulatory peptide in patients with solid tumor malignancies: a phase I trial. 953 10

DACA, also known as XR5000, is an acridine derivative active against both topoisomerase I and II. In this phase I study, DACA was given as a 3-h intravenous infusion on 3 successive days, repeated every 3 weeks. A total of 41 patients were treated at 11 dose levels between 9 mg m(-2) d(-1) and the maximum tolerated dose of 800 mg m(-2) day(-1). The commonest, and dose-limiting, toxicity was pain in the infusion arm. One patient given DACA through a central venous catheter experienced chest pain with transient electrocardiogram changes, but no evidence of myocardial infarction. At the highest dose levels, several patients also experienced flushing, pain and paraesthesia around the mouth, eyes and nose and a feeling of agitation. Other side-effects, such as nausea and vomiting, myelosuppression, stomatitis and alopecia, were uncommon. There was one minor response but no objective responses. DACA pharmacokinetics were linear and did not differ between days 1 and 3. The pattern of toxicity seen with DACA is unusual and appears related to the mode of delivery. It is possible that higher doses of DACA could be administered using a different schedule of administration.
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PMID:Phase I and pharmacokinetic study of DACA (XR5000): a novel inhibitor of topoisomerase I and II. CRC Phase I/II Committee. 1046 97

The alkylating agent chlorambucil produces dose-limiting myelosuppression but can also cause rare central nervous system toxicities, including seizures, when given in high doses. Patients with lymphoma who were receiving intermittent pulsed oral doses of 10-12 mg/m2 chlorambucil per day for 5 days experienced marked mood alterations during therapy. These effects, which have not been reported previously, involved sleep alterations, anxiety and restlessness, irritability, and depression. All effects remitted immediately after the final day of the dosing regimen. Mood alterations should be added to the known list of chlorambucil-related toxicities and can occur with commonly used oral dosing schedules.
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PMID:Mood alterations in patients treated with chlorambucil. 1471 1