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Query: CAS:65886-71-7 (Fazarabine)
 9 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fazarabine is a synthetic analog of cytosine arabinoside and 5-azacytidine that incorporates structural features of both compounds. Xenograft studies showed good activity against a variety of transplanted tumors. Initial studies in adults employed both a continuous infusion schedule and a daily bolus x 5 schedule. Myelotoxicity, especially neutropenia, was dose-limiting, with excessive myelotoxicity seen on the daily bolus x 5 at 72 mg/M2/day. Since short infusions may be administered in Ringer's lactate rather than either dimethylsulfoxide or dimethylacetamide required for continuous infusion, this study examined a daily x 5 schedule in children with refractory solid tumors. The initial dosage was 30 mg/M2/day, 80% of the maximum tolerated dosage in adults, with subsequent 30% dosage escalations. A total of 18 patients were enrolled, with a wide spectrum of pediatric solid tumors. Myelosuppression was the only significant toxicity, and was excessive at 78 mg/M2/day. Therefore, on this bolus regimen, 65 mg/M2/day for 5 days was the maximum tolerated dosage. One patient with medulloblastoma had stable disease for 65 days. No other responses were seen.
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PMID:A phase I trial of fazarabine in refractory pediatric solid tumors. A Pediatric Oncology Group study. 751 39

Promising preclinical data and reasonable toxicity in Phase I trials encouraged the Gynecologic Oncology Group to study Fazarabine (FZB) in patients with recurrent squamous cell cancer of the cervix. Twenty-three patients with histologically proven recurrent cervical cancer with measurable disease received FZB at a dosage of 30 mg/m2 per day for 5 days; cycles repeated every 28 days. In the absence of grade 3 or 4 toxicity, dose escalation was planned to a maximum dose of 40 mg/m2 per day for 5 days. All patients were evaluable for toxicity. Seven patients developed neutropenia; in two instances, it was considered life-threatening. The only other serious adverse effect was seen in one patient who developed grade 4 nephrotoxicity. Nineteen women who had failed prior chemotherapy were evaluable for response. There were no complete or partial responses; and seven had stable disease. Fazarabine exhibits no demonstrable activity in this patient population at the dose and schedule tested and further clinical trials as second-line chemotherapy are not warranted.
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PMID:A phase II study of fazarabine (NSC 281272) in patients with advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study. 757 64

Fazarabine (Arabinofuranosyl-5-azacytosine) is a synthetic pyrimidine nucleoside which combines the arabinose sugar of cytosine arabinoside with the triazine base of 5-azacytidine. It has demonstrated activity against a variety of human solid tumor xenografts including colon, lung and breast cancers. Eighteen patients with refractory metastatic colon cancer were enrolled in a phase II trial of fazarabine. The drug was administered as a 72 hr continuous infusion every 3-4 weeks; the starting dose was 2 mg/m2/hr as established in a previous phase I study. The major toxicity was neutropenia, as predicted from the phase I study. The median time to nadir for cycle 1 was 20 days, with a median granulocyte count of 437/microliters (range 36-1600/microliters); recovery was within 2-4 days, with only one incidence of fever and neutropenia in 42 cycles. Especially noted for their absence were thrombocytopenia, nausea, vomiting and stomatitis. No objective clinical responses were seen; one patient had stabilization of rapidly growing liver metastases for a period of 7 months. In view of fazarabine's narrow range of toxicities, future dose intensification trials utilizing fazarabine in combination with hematopoietic growth factors are worthy of consideration.
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PMID:Phase II study of fazarabine (NSC 281272) in patients with metastatic colon cancer. 768 14

Fazarabine (1-beta-D-arabinofuranosyl-5-aza-cytosine, or Ara-AC) is a nucleoside analogue that consists of the arabinoside ring of 1-beta-D-arabinofuranosylcytosine and the pyrimidine base of 5-azacytidine. In Phase I and Phase II trials, neutropenia was dose limiting, with minimal nonhematological toxicity. The in vitro cytotoxic concentrations of Ara-AC could not be achieved in these studies; neutropenia precluded dose escalation. The objectives of this study were: to determine either the maximum tolerated dose of Ara-AC or to safely achieve target plasma levels of 2-5 microgram/ml when Ara-AC was administered as a 24-h infusion with granulocyte colony-stimulating factor (G-CSF) to patients with advanced refractory malignancies; to characterize the pharmacokinetic behavior of Ara-AC with G-CSF; and to define the relationship of Ara-AC pharmacokinetics to toxicity. Twenty-four patients received 67 courses of Ara-AC at doses of 54-112 mg/m2/h. Dose-limiting toxicity was approached but not reached. Grade 3 or 4 neutropenia and nausea were the principle side effects. Steady-state plasma concentrations exceeded the minimum target concentration of 2 microgram/ml in all patients who received >/=78 mg/m2/h for 24 h. The maximum target concentration was approached during administration of 112 mg/m2/h for 24 h. The mean steady-state clearance was 475 +/- 103 ml/min/m2 and did not change with dose. One partial response was seen. One patient received 16 courses and another received 7 courses of therapy before progression. Ara-AC can be safely administered in doses that result in plasma concentrations of 2-5 microgram/ml, if it is given with G-CSF. Phase II trials of Ara-AC in selected malignancies are planned.
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PMID:Phase I and pharmacological trial of fazarabine (Ara-AC) with granulocyte colony-stimulating factor. 981 35