Disease relevance of Maximum Tolerated Dose

• PURPOSE: The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose of pentosan polysulfate in patients with HIV-associated Kaposi's sarcoma and whether or not this compound had activity against this neoplasm [1].
• In a double-blind crossover trial, (-)-deprenyl, a fast-acting selective monoamine-oxidase-B inhibitor without a "cheese effect", was given to 41 patients with idiopathic Parkinson's disease who were receiving maximum tolerated doses of levodopa either alone or combined with carbidopa ("Sinemet") [2].
• METHODS: One hundred eighteen cirrhotics with esophageal varices were blindly randomized to receive 20 mg of isosorbide-5-mononitrate three times a day (n = 57) or propranolol (n = 61) up to the maximum tolerated dose [3].
• More significantly, dEpoB (25-40 mg/kg, Q2Dx5, i.p.) showed far superior therapeutic effects and lower toxicity than paclitaxel, doxorubicin, camptothecin, or vinblastine (at maximal tolerated doses) in parallel experiments [4].
• Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days [5].

Psychiatry related information on Maximum Tolerated Dose

• To test the acute therapeutic efficacy of cholinergic replacement, seven patients with presenile onset of Alzheimer's type dementia received maximum tolerated doses (10 mg/d) of the selective muscarinic agonist, RS-86, in combination with a peripherally active anticholinergic glycopyrrolate (6 mg/d), in a double-blind placebo-controlled design [6].
• Establishing the maximum tolerated dose of lesopitron in patients with generalized anxiety disorder: a bridging study [7].
• Safety and tolerability of metrifonate in patients with Alzheimer's disease: results of a maximum tolerated dose study [8].

High impact information on Maximum Tolerated Dose

• Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect [9].
• But clinical trials in cancer patients have on the whole been disappointing, and it has been estimated that a TNF dose would be effective only at 5-25 times the maximum tolerated dose [10].
• PURPOSE: The purpose of this study was to determine the maximum tolerated dose and the toxic effects of cyclophosphamide administered every 2 weeks with GM-CSF support [11].
• RESULTS: The maximally tolerated dose of pentosan polysulfate given by continuous venous infusion was found to be 3 mg/kg per day [1].
• PURPOSE: Our objectives in this study were to determine the maximum tolerated dose of ADR-529 (which uses a different vehicle than ICRF-187) when given with a fixed doxorubicin dose and to determine whether ADR-529 alters doxorubicin pharmacokinetics [12].

Chemical compound and disease context of Maximum Tolerated Dose

• In the phase I/II pediatric hydroxyurea safety trial (HUG-KIDS), school-aged children with sickle cell anemia receiving hydroxyurea at the maximally tolerated dose (MTD) had variable increases in the percentage of fetal hemoglobin (%HbF) [13].
• The concomitant administration of dexamethasone increased the maximum tolerated dose of IL-2 approximately threefold and markedly reduced the hypotension and organ dysfunction ordinarily observed in these patients [14].
• We conclude that allopurinol given in the proper dose and schedule can diminish the granulocytopenia produced by bolus doses of 5-FU, thereby allowing a 50% increase in the maximal tolerated dose of 5-FU [15].
• Two combination phase I trials were undertaken to determine the maximum tolerated dose of CPT-11 in combination with cisplatin and vindesine in patients with advanced non-small cell lung cancer [16].
• Nevertheless, carboplatin and ifosfamide can be combined at 80% and 75% of the single-agent maximum-tolerated doses, respectively, with acceptable nonhematologic toxicity [17].

Biological context of Maximum Tolerated Dose

• After inhalation of nitric oxide (10-20 ppm), we assigned patients to either maximum tolerated dose of intravenous epoprostenol (mean 8.0 ng/kg per min; n=8) or oral sildenafil (50 mg; n=8) [18].
• The initial IFN dose of 3 x 10(6) U/m2/d was escalated to the maximum tolerated dose or to a maximum of 6 x 10(6) U/m2/d. IFN controlled the white blood cell (WBC) counts in 14 of 16 patients who had abnormal counts, and in all six patients with an elevated platelet count [19].
• The maximum-tolerated dose of carboplatin was AUC 16 (equivalent to a median of 1,189 mg/m(2)) [20].
• We conducted a phase I trial of concurrent subcutaneous (SC) administration of IL-12 and IFN-alpha-2b in patients with metastatic RCC or MM to determine toxicity, maximum-tolerated dose, preliminary efficacy, and effects on chemokine/cytokine gene expression in peripheral blood mononuclear cells (PBMCs) [21].
• PURPOSE: To determine the maximal-tolerated dose (MTD) of topotecan with cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in these patients [22].

Anatomical context of Maximum Tolerated Dose

• PURPOSE: A dose-escalation study was conducted to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cyclophosphamide (CY) in combination with granulocyte colony-stimulating factor (G-CSF0 and doxorubicin (DOX) given every 2 weeks for eight cycles as outpatient adjuvant therapy for node-positive breast cancer [23].
• A significant decrease in peripheral blood platelet counts was caused by the maximum tolerated doses (MTD) of carboplatin alone and with WBH [24].
• High rates of central nervous system (CNS) toxicity and neutropenia occurred in both minimally and heavily pretreated patients who were treated with CI-980 doses above 3.75 mg/m2/day, which is the maximum tolerated dose and the recommended dose for additional evaluations [25].
• PURPOSE: To determine the toxicity, maximal tolerated dose, and clinical and immunologic response to autologous dendritic cells pulsed with melanoma-associated antigen gp100-derived G280-9V peptide [26].
• METHODS: Adenosine (15 mg, a maximally tolerated dose, n = 10) was infused over six minutes via a coronary artery and compared with saline (n = 12) in anaesthetised rabbits [27].

Associations of Maximum Tolerated Dose with chemical compounds

• At the maximally tolerated dose, 5'-dFUrd (500 mg/kg/day) and FUra (25-35 mg/kd/day) were equally effective in producing cures when treatments were performed by either continuous iv infusion or iv push [28].
• We therefore studied the effects of oral metoclopramide given at doses of 20, 50, or 100 mg four times a day for 25 doses (7 days) beginning after cisplatin to determine the maximum tolerated dose (MTD) for prophylactic oral antiemetic regimens [29].
• To determine the maximum tolerated dose of 5-FU with leucovorin for use in combination with cyclophosphamide and doxorubicin, we conducted a phase I/II trial in 20 patients [30].
• The maximum tolerated dose was 6 g of cyclophosphamide/m2 and 720 mg of thiotepa/m2 [31].
• Failure of high-dose leucovorin to improve therapy with the maximally tolerated dose of 5-fluorouracil: a murine study with clinical relevance [32]?

Gene context of Maximum Tolerated Dose

• CONCLUSIONS: We conclude that 10 micrograms/kg per dose of IL-4 is the maximum-tolerated dose for this schedule, although 15 micrograms/kg per dose can be tolerated if more intensive, but still non-intensive care unit level care is provided [33].
• PURPOSE: This phase I clinical trial was designed to determine the maximum-tolerated dose and dose-limiting toxicities of the matrix metalloproteinase (MMP) inhibitor COL-3 in patients with refractory solid tumors [34].
• PURPOSE: To determine the toxicity, maximum-tolerated dose (MTD), and pharmacokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Corp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation [35].
• These data suggest that the antiangiogenic activity of IFN-alpha is dependent on frequent administration of optimal biological dose and not maximal tolerated dose [36].
• Pretreatment with the MGMT inactivators BG or dBG reduced the maximum-tolerated doses of BCNU and TMZ to 35 and 170 mg/m(2), respectively [37].

Analytical, diagnostic and therapeutic context of Maximum Tolerated Dose

• Chemotherapy consisted of the maximum tolerated dose of gemcitabine (i.v., 100 mg/kg, q3dx4) [38].
• The primary end point was the determination of the maximum-tolerated dose (MTD) of twice weekly gemcitabine with concurrent radiotherapy [39].
• The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days [40].
• For animals bearing SF767 xenografts, the tumor growth of controls was not significantly different from that of animals treated with O6-benzylguanine alone or BCNU alone up to the maximally tolerated dose (50 mg/kg) [41].
• The maximum-tolerated dose of IT mafosfamide following premedication with dexamethasone and morphine was 14 mg [42].

References