Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the anticancer agent flavone acetic acid (FAA), we conducted a Phase I trial involving 17 pediatric patients with various malignant solid tumors. Dosages investigated included 5,120 and 6,144 mg/m2 given as 3-hour intravenous infusions; and 10,000, 12,500, 15,000, and 17,500 mg/m2 delivered in a 24-hour constant infusion with alkalinization. Grade 2 or worse toxicity was minimal, with 2 patients having nausea/vomiting, 2 having diarrhea, 1 becoming hypertensive, 1 becoming hypotensive, and 2 having myalgia. Three patients who received a 17,500 mg/m2 dose had no toxicity. Disease was stabilized for a brief period in 2 patients--1 with brain stem glioma and 1 with astrocytoma. The FAA pharmacokinetics varied with an average (SD) terminal half-life of 27.9 hr (18.7), clearance of 2.04 L/hr/m2 (0.37), and steady-state volume of 19.9 L/m2 (10.6). This study was discontinued because FAA caused no significant toxicity or therapeutic responses at doses 2.5 gm/m2 greater than had been tolerated by adults.
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PMID:Phase I study of flavone acetic acid (NSC 347512, LM975) in patients with pediatric malignant solid tumors. 195 36

KRN8602(MX2) is a newly developed morpholino-anthracycline that has been found to cross the blood-brain barrier and be distributed in brain tissue after intravenous administration and to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo. In order to confirm these promising preclinical observations clinically, we performed a phase II trial of KRN8602 in patients with recurrent malignant glioma. The 44 patients enrolled received at least 2 cycles of KRN8602 35 mg/m2/day at 3-4 week intervals by intravenous bolus. Of the 44 patients, 37 could be evaluated for response, and 39 for toxicity. One patient with anaplastic astrocytoma had a complete response (1/37, 3%), and 2 patients with anaplastic astrocytoma and 1 with brain stem glioma had a partial response (3/37, 8%). The overall response rate was 11% (4/37). All patients who responded had received prior chemotherapy that included nitrosoureas. No response was observed in the patients with glioblastoma. Myelosuppression was moderately severe, with 72% of patients developing grade 3 or 4 leukopenia. Severe nausea/vomiting was observed in 31% of the patients. No severe cardiotoxicity was observed. The results indicate that KRN8602 has modest activity against recurrent malignant glioma with relatively severe, but manageable toxicity. It seems to be worthwhile to further assess the efficacy and toxicity of KRN8602 against malignant glioma, which is generally less sensitive to chemotherapy.
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PMID:A phase II study of KRN8602(MX2), a novel morpholino anthracycline derivative, in patients with recurrent malignant glioma. 1042 Oct 76

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age approximately 13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m(-2)/150 mg m(-2) day(-1), 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1-7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin-temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m(-2) cisplatin and 150 mg m(-2) x 5 temozolomide in heavily treated, and 200 mg m(-2) x 5 temozolomide in less-heavily pretreated children.
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PMID:Dose finding and O6-alkylguanine-DNA alkyltransferase study of cisplatin combined with temozolomide in paediatric solid malignancies. 1613 28