Phase I study of terameprocol in patients with recurrent high-grade glioma

Phase I study of terameprocol in patients with recurrent high-grade glioma

A nontoxic, therapeutic agent having pharmacological activity comprising concentrated extract of Larrea tridentata plant material and ascorbic acid, an ascorbic acid ester, an ascorbic acid salt, butylated hydroxyanisole, butylated hydroxytoluene, hydrogen sulfide, hypophosphorous acid, monothioglycerol, potassium bisulfite, propyl gallate, sodium bisulfite, sodium hydrosulfite, sodium thiosulfate, sulfur dioxide, sulfurous acid, a tocopherol, or vitamin E is made by a process in which the plant material is extracted using an organic solvent, preferably acetone, and is then saturated with one of the listed reducing agents acid to reduce the toxic NDGA quinone, which naturally occurs in the plant material, to NDGA itself. The leaves are ovate, acute, dentate, subcordate upon the stem opposite and supported upon long petioles. Then, for fun, take a look around the blog, too. The resulting compound can also be used as an anti-inflammatory when the inflammatory diseases are mediated by the effects of leukotrienes. Humans of different places, times, and faiths have been deeply stirred by the beauty with which Spring returns, celebrating it with the Equinox, Easter, passover, and even the ides of March, which was originally the Roman New Year. – Worse still maybe you possessed a really helpful doctor like I did that casually told me that i should not ever have sex again.|Since publishing the result I received was basically staggering very inspiring. –20/27 using poly E ointment vaginally 2x/week –6/8 poly E plus poly E capsule –3/6 poly E capsule –6/10 EGCG capsule Overall: 69% response rate 35/51 with green tea extract vs 10 % response rate 4/39 in controls (P 18 years with two to 30 EGWs applied vehicle Polyphenon E ointment 10% or Polyphenon E ointment 15% three times daily until complete clearance of all EGWs (baseline + new EGWs) or for a maximum of 16 weeks.

Patients taking enzyme-inducing antiseizure drugs (EIASDs) were escalated independently. After few weeks the fluid as well. A daily therapeutic dosage would be approximately 300 mg. Some Guidelines on Prophecy by Keth  Appropriate articles may be submitted by emailing them to Keth at News @ Awakening-Healing.com. To my fellow swimmers, There is a river flowing now very fast. The **Tlazolteotl has eaten all the poison. Although no responses were seen, stable disease was noted in 9 (28%) of 32 evaluable patients, with 5 (13%) continuing treatment for >6 months (≥6, 8, 10, 10, and ≥21 months).

Researchers have found that the ratio of the amino acids arginine and lysine plays an important part in controlling (not curing!) cold sores. Results from these trials have been encouraging and Phase II studies are being planned. Preclinical and human data suggest that this novel transcription inhibitor is worthy of further study. 2,373,192, incorporated herein by reference), until the GRAS (Generally Recognized As Safe) status of NDGA was revoked after animal studies revealed evidence of kidney toxicity resulting from the ingestion of NDGA. NDGA is known as a powerful antioxidant compound. Andrew Weil recommends the use of Chaparral in a douche (a tsp. Extracts and preparations from the creosote bush Larrea tridentata, found in the deserts of the southwestern United States and Mexico, have been ingested for generations by Native Americans to treat various medical disorders.2,3 Its leaves are used to make chaparral tea, which has been administered orally for cancer, venereal disease, tuberculosis, colds, and rheumatism.

However the virus that is unnatural. I know that for a fact because I have genital herpes. tridentata can result in reversible hepatic damage.5 Another preparation of NDGA (10% masoprocol cream [Actinex]) was Food and Drug Administration approved for actinic keratosis and was voluntarily withdrawn by the manufacturer because of lack of sales and some local and reversible skin reactions. Vemma has Vitamin C, D, E, A, B12, B6, iron, riboflavin, thiamin, pantothenic acid, niacin and folate. A phase I study of intralesional terameprocol in patients with recurrent and refractory head and neck cancer administered weekly injections each designed to deliver 20 mg of terameprocol per cubic centimeter of tumor.18 In 5 of the 6 patients who completed 3 doses of terameprocol, the tumor became necrotic without injury to adjacent tissues. Shegoi utilizes the healing power of the Larrea tridentata plant in a topical application. The local efficacy after intratumoral administration and documentation of systemic absorption without local or systemic toxicities prompted the development of systemic formulations.

Escalating doses of intravenous terameprocol administered for 5 consecutive days each month were studied in patients with advanced systemic cancers.19 Metabolic acidosis was noted at a daily dose of 3300 mg, which was felt to be secondary to conversion of the excipient polyethylene glycol 300 (PEG 300) to oxalic acid. An additional phase I study of refractory solid tumors administered up to 4200 mg of terameprocol over a 24-h infusion period using a schedule of 1 dose day per week for 3 weeks, followed by 1 week of rest.20 Another study in patients with advanced hematologic malignancies found the maximum tolerated dose (MTD) to be 1500 mg 3 times weekly for 2 of every 3 weeks.21 A partial response was observed in each of the latter 2 studies. We report the results of a phase I study of terameprocol in patients with recurrent high-grade gliomas. This study was conducted by the New Approaches to Brain Tumor Therapy CNS Consortium and funded by the National Cancer Institute (National Institutes of Health, CA-62475 New Approaches to Brain Tumor Therapy CNS Consortium, to P.I.G.). Also, potential medical uses based on the effects of NDGA on the cardiovascular, immune and neurological systems; cancer; tissue engineering; as well as pharmacokinetics and toxicity are discussed. Lee Moffitt Cancer Center). Bacterial strains used were clinical isolates of MSSA (n = 100) and MRSA (n = 100) isolated from St George’s Hospital, London.

The primary objective of this study was to determine the MTD of terameprocol administered as a daily intravenous infusion for 5 consecutive days every 28 days to adults with recurrent high-grade glioma. The results of this investigation revealed that tetra-O-methyl NDGA (also known as M4N or terameprocol (TMP)) displayed the highest level of anti-HIV activity [25]. If they experience either improvement, or a worsening of their symptoms (as a result of a Jarisch-Herxheimer or “Herx” reaction) after their treatment, then they may still be infected with Babesia despite their negative lab test results. Patients were excluded if they had a serious concurrent medical illness, infection, or malignancy; if they had a known sensitivity to terameprocol, PEG 300, or hydroxypropyl-β-cyclodextrin; or if they were pregnant, breast-feeding, or receiving other anticancer therapy for their brain tumor. An interval of at least 3 months must have elapsed since the completion of radiation therapy, 3 weeks since nonnitrosourea chemotherapy, and 6 weeks since nitrosourea chemotherapy. Food and Drug Administration (FDA) removed chaparral from the “Generally Recognized as Safe” (GRAS) list in 1970, and considers chaparral to be unsafe. This may be why coastal peoples kept the fresh root pieces to chew on daily as a whole-body tonic much in the tradition of ginseng; plus, in the rainforest, keeping dried herbs was a trifle more elaborate than in more xeric habitats such as Hopi land.

Liver and kidney herbs can support medication-associated toxic stress. Caution is advised in patients with diabetes or hypoglycemia and in those taking drugs, herbs, or supplements that affect blood sugar. Patients in the −EIASD group were either not being treated with an antiseizure drug or were taking one that does not significantly induce hepatic enzymes, such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide, and felbamate. For purposes of this study, the +EIASD group included patients taking phenytoin, carbamazepine, phenobarbital, primidone, and oxcarbazepine. Inclusion in the −EIASD group required patients to discontinue using any +EIASD for at least 10 days. Drug doses in these 2 patient groups were escalated independently. A standard phase I design was used with cohorts of 3 patients treated at each dose level and monitored for treatment-related toxicities.

Phase I study of terameprocol in patients with recurrent high-grade glioma
Escalation to the next dose proceeded in the absence of dose-limiting toxicities (DLTs). If a DLT occurred, an additional 3 patients were added at the same dose, and dose escalation continued if there were no DLTs in these patients. The MTD was considered to have been exceeded if >1 patient in a cohort (3–6 patients) experienced a DLT, thereby establishing the previous dose as the MTD. For purposes of this study, a DLT was defined as any of the following treatment-related adverse events occurring in the first cycle of therapy: (1) absolute neutrophil count ≤500 neutrophils/mm3, (2) platelet count ≤25 000 platelets/mm3, (3) febrile neutropenia, (4) any grade 3 or 4 nonhematologic toxicity, or (5) a delay in starting a subsequent course of treatment for >14 days because of incomplete recovery from toxicity. The starting dose of terameprocol in both patient groups was 750 mg/day for 5 consecutive days each month by intravenous infusion. Further prespecified dose escalations were 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300 mg/day. Hepar sulphuris calcareum (calcium sulphide) This remedy is suitable for eruptions around mouth and lips, occasionally following the path of the nerves across the face or even around or into the eyes.

Salves concocted with various parts of the plant were used to treat rashes, venomous bites and open wounds. iHeartLilyNerves is also a diuretic that doesn’t remove potassium from the body like other diuretics. Patients were considered to be evaluable for toxicity if they received 100% of the prescribed dose during their first month of treatment and were replaced if they withdrew before completing the first cycle for reasons other than toxicitiy. (A warm, sunny car can range from 100-200 degrees depending on the outdoor temps, sun exposure and where you place the oil (windshield, floor, shady spot).) Strain through cheesecloth or clean muslin, squeezing out as much oil as you can (and again through a coffee filter, if desired) to desired clarity. The terameprocol dosing schedule was chosen on the basis of information and advice from Erimos Pharmaceuticals. Terameprocol was infused though a central or peripheral line at 150 mL/hour using a terameprocol-compatible infusion system provided by Erimos Pharmaceuticals. Antiemetics were not administered, and anticonvulsants and corticosteroids were administered as clinically indicated.

If a patient developed a DLT, a subsequent dose of terameprocol could be administered after resolution of the toxicity by lowering the dose to the previous dose level. Failure to tolerate the lowest dose (750 mg/day) resulted in the patient being withdrawn from the study. Because terameprocol is poorly soluble in water, it was formulated for intravenous administration as a 10 mg/mL solution in a vehicle composed of PEG 300, hydroxypropyl-β-cyclodextrin, and water for intravenous administration (designated as CPE). In previous clinical trials of this agent using the CPE formulation, patients frequently developed a reversible metabolic acidosis attributable to the metabolism of the PEG. vol. He took this as an infusion and within a week he was sleeping well. With the conversion to the new formulation, one additional cohort of patients was added using TC6 formulation at the last terameprocol dose administered with CPE (Table 2).

ACAD. Blood was collected in tubes without an anticoagulant and permitted to clot for approximately30 min before centrifuging (1200–1500 × g, 15 min, 4°C). The serum was removed and stored at −20°C until thawed for analysis by high performance liquid chromatography with tandem mass spectrometry by Covance Bioanalytical Services. The lower limit of quantitation of the analytical method was 10 ng/mL, for which the interday accuracy and precision were 98.8% and 3.5%, respectively. Serum concentration-time profiles of the drug for individual patients were fit to model-independent equations for continuous intravenous drug input with either bi- or triexponential first-order elimination by weighted nonlinear regression using WinNonlin Professional software, version 5.0 (Pharsight).22 Final values of the iterated parameters in the best-fit equation were used to calculate all pharmacokinetic variables according to standard equations.23 The paired 2-tailed t test was used to compare mean pharmacokinetic variables between the −EIASD and +EIASD treatment groups after logarithmic transformation of the data. P < .05 was the criterion for statistical significance. Tumor response and progression were categorized using the Macdonald criteria.24 Patients were defined as having progressive disease if there were (1) new lesions on serial neuroimaging studies, (2) >25% increase in the bidirectional measurement of contrast-enhancing tumor on MRI or CT, or (3) progressive neurologic abnormalities that could not be attributed to etiologies other than tumor progression.

Overall survival was assessed using the Kaplan-Meier method.25 Patients who had not died prior to data cutoff were censored at the last date on which they were known to be alive. A total of 35 patients participated in to this research study during 2007–2008. Sixteen (46%) of these patients were male, 32 were white, 2 were African American, and 1 was Asian. They had a median age of 46 years (range, 29–71 years) and a median Karnofsky performance status of 80 (range, 60–100) and had received a median of 2 prior chemotherapy regimens (range, 1–6). Can be used after Nat mur to finish off the cold sore. A summary of the total number of patients treated and the number of observed DLTs as a function of dose, formulation, and EIASD administration is presented in Table 1. A summary of observed toxicities is provided in Table 2.

The identity and mode of action of these synergistic compounds is unknown but they may facilitate absorption of the antiviral lignans or otherwise enhance the specific physiological antiviral effects. Henderson, The Role of Leukotrienes in Inflammation, ANN. At 2200 mg, 1 of 3 patients developed a grade 3 ileus, and thus, another 3 patients were added to the cohort. One of these developed grade 3 dyspnea. These patients were treated for 1, 1, 1, 2, 2, and 4 months. Because 2 of 6 patients at the 2200 mg dose level had DLTs, the MTD with the PEG formulation was determined to be 1700 mg/day. After reformulation to a PEG-free infusion, 3 additional patients were treated at 1700 mg without DLTs for 2, 2, and 6 months.

A total of 14 patients participated in the +EIASD cohort. These patients were receiving phenytoin (10), carbamazepine (3), and oxcarbazepine (1). No DLTs were seen in 3 patients treated at 750 mg/day. These patients received 1, 2, and 8 months of treatment before developing progressive disease. Four patients were treated at a dose of 1100 mg/day, because 1 of the first 3 patients accrued was inevaluable for the toxicity evaluation and was replaced. No DLTs were observed, and they were treated for 1, 1, and 10 months before developing progressive disease. Three patients were treated at 1700 mg/day, and 2 were treated at 2200 mg/day without DLTs.

Treatment durations for these patients were short (1, 1, 2, 1, and 2 months) because of progressive disease. Secondly, NDGA affects gene expression and differentiation, which is likely through its effects on leukotriene synthesis [2]. Thus, the drug was reformulated as described above to prevent moresevere acidosis. With the new PEG-free formulation, the regimen was reinstituted at 1 dose level below the prior dose. Thus, 2 patients were treated at 1700 mg/day without toxicities for 3 and 4 months. Briefly, approximately 100 U/ml of ovine COX-2 (Cayman Chemical Co., Ann Arbor, MI) was mixed with an assay buffer containing 100 mM Tris-HCl pH 8.0, 1 μM bovine hemin and the inhibitor TMP. The B-12 supports the immune system and is also energizing.

There were no differences between any of these parameters that approached statistical significance, suggesting that the concurrent administration of EIASD does not have a clinically significant effect on the serum pharmacokinetics of terameprocol. As a result, the study was closed, with the recommended dose of the PEG-free formulation being 1700 mg per day for 5 consecutive days each month. J Altern Complement Med 2001;7(2):175-185. Handsome well-behaved evergreen horticultural varieties abound as ornamentals and streamside and roadside erosion control plantings. Therapies to stimulate the immune system, such as ozone infusion therapy, are vital as well given that the immune system needs to be operating at full capacity to speed recovery and prevent recurrence.

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Phase I study of terameprocol in patients with recurrent high-grade glioma

Phase I study of terameprocol in patients with recurrent high-grade glioma

ANSWER: As you found out, Shingles and PHN are caused by the Herpes Zoster virus. Background Chaparral is a shrub found in the desert regions of southwestern United States and Mexico. Their respective strong antimicrobial and antiectoparasite activities have made them extremely useful in combating disease organisms large and small. Other than resulting in time and money invested to heal someone physically, it can hurt emotionally and mentally. Chaparral leaves have also been used externally for bruises, scratches, wounds, and hair growth. Su aj ine silne zname ako betulin a huba chaga, ale zatial su prakticky nepristupne, lebo ich vyroba a rozsirovanie sa znacne blokuje. While research has suggested that some of the lignans present in the plant resin possess both antimicrobial, anti-inflammatory and antioxidant properties, it is NDGA that has been the focus of most research into the efficacy of the plant.

Hypoxia and interstitial nephritis were noted at 2200 mg/day. Concurrent administration of EIASD did not significantly affect the serum pharmacokinetics of the terameprocol. Although no responses were seen, stable disease was noted in 9 (28%) of 32 evaluable patients, with 5 (13%) continuing treatment for >6 months (≥6, 8, 10, 10, and ≥21 months). A role, now played by synthetic antioxidants such as BHT and BHA. This phase I study defined the toxicity of terameprocol, determined that EIASDs do not affect its pharmacokinetics, and identified 1700 mg/day as the dose for future studies. Preclinical and human data suggest that this novel transcription inhibitor is worthy of further study. The long-term stability noted in some patients and the lack of associated myelosuppression suggest that terameprocol could be safely combined with radiation and temozolomide in newly diagnosed high-grade gliomas.

– Chronic: to 1 cup, 3 times a day. A unique patented extraction and processing method has turned an ancient desert plant, Larrea Tridentata into an extraordinary health enhancing formula. Apply ice every ten minutes for an hour. Dr. Halts oxidation, especially the toxicity of a free radical known as singlet oxygen. tridentata can result in reversible hepatic damage.5 Another preparation of NDGA (10% masoprocol cream [Actinex]) was Food and Drug Administration approved for actinic keratosis and was voluntarily withdrawn by the manufacturer because of lack of sales and some local and reversible skin reactions. Pros: Fast, highly effective extraction, especially for more alcohol-soluble constituents.

A phase I study of intralesional terameprocol in patients with recurrent and refractory head and neck cancer administered weekly injections each designed to deliver 20 mg of terameprocol per cubic centimeter of tumor.18 In 5 of the 6 patients who completed 3 doses of terameprocol, the tumor became necrotic without injury to adjacent tissues. Pharmacokinetic studies documented systemic absorption of the terameprocol, with peak plasma concentrations 2 h after these intratumoral injections. The local efficacy after intratumoral administration and documentation of systemic absorption without local or systemic toxicities prompted the development of systemic formulations. Genotyping of these strains were performed previously (Hu et al., 2015). An additional phase I study of refractory solid tumors administered up to 4200 mg of terameprocol over a 24-h infusion period using a schedule of 1 dose day per week for 3 weeks, followed by 1 week of rest.20 Another study in patients with advanced hematologic malignancies found the maximum tolerated dose (MTD) to be 1500 mg 3 times weekly for 2 of every 3 weeks.21 A partial response was observed in each of the latter 2 studies. We report the results of a phase I study of terameprocol in patients with recurrent high-grade gliomas. The local efficacy after intratumoral administration and documentation of systemic absorption without local or systemic toxicities prompted the development of systemic formulations.

. Veterinary surgeons added their support to this use of the herb. Erimos Pharmaceuticals provided the terameprocol and compatible infusion tubing for the administration of this drug. 15, pp. The secondary objectives were to (1) determine the effects of hepatic enzyme-inducing antiseizure drugs (EIASD) on the pharmacokinetics of this agent, (2) estimate the toxicity and tolerability associated with terameprocol, and (3) assess antitumor activity in terms of overall survival. Eligible patients were at least 18 years of age with histologically proven malignant glioma (anaplastic astrocytoma, anaplastic oliogodendroglioma, or glioblastoma multiforme) progressive or recurrent after radiation with or without chemotherapy. Patients were required to have contrast-enhancing measurable disease by MRI or CT imaging and must have recovered from toxicities of prior therapy.

An interval of at least 3 months must have elapsed since the completion of radiation therapy, 3 weeks since nonnitrosourea chemotherapy, and 6 weeks since nitrosourea chemotherapy. You always want to check the weather will turn brownish which later dry out the affected child. Russell Jordan (see Chapter One of Meditopia), I learned of its medicinal properties and found myself as if reconnected to an old friend . Patients were excluded if they had a serious concurrent medical illness, infection, or malignancy; if they had a known sensitivity to terameprocol, PEG 300, or hydroxypropyl-β-cyclodextrin; or if they were pregnant, breast-feeding, or receiving other anticancer therapy for their brain tumor. Eligible patients were assigned to 1 of 2 treatment groups (−EIASD or +EIASD) on the basis of their use of antiseizure drugs. Patients in the −EIASD group were either not being treated with an antiseizure drug or were taking one that does not significantly induce hepatic enzymes, such as gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine, topiramate, zonisamide, and felbamate. For purposes of this study, the +EIASD group included patients taking phenytoin, carbamazepine, phenobarbital, primidone, and oxcarbazepine.

If you do this when you feel a burning or itching at the onset of the cold sore, this remedy may inhibit the formation of the lesion. Drug doses in these 2 patient groups were escalated independently. A standard phase I design was used with cohorts of 3 patients treated at each dose level and monitored for treatment-related toxicities. ACAD. 51, pp. No genetically modified organisms (GMO’s) are involved. For purposes of this study, a DLT was defined as any of the following treatment-related adverse events occurring in the first cycle of therapy: (1) absolute neutrophil count ≤500 neutrophils/mm3, (2) platelet count ≤25 000 platelets/mm3, (3) febrile neutropenia, (4) any grade 3 or 4 nonhematologic toxicity, or (5) a delay in starting a subsequent course of treatment for >14 days because of incomplete recovery from toxicity.

Phase I study of terameprocol in patients with recurrent high-grade glioma
The starting dose of terameprocol in both patient groups was 750 mg/day for 5 consecutive days each month by intravenous infusion. Further prespecified dose escalations were 1100, 1700, 2200, 3000, 4000, 5300, 7000, and 9300 mg/day. No intrapatient dose escalations were permitted. An analysis of the pharmacokinetic results was planned after accrual to the initial dose levels. If this revealed no significant EIASD effect on the pharmacokinetics of terameprocol, the use of separate +EIASD and −EIASD cohorts for dose escalation would be discontinued. Patients were considered to be evaluable for toxicity if they received 100% of the prescribed dose during their first month of treatment and were replaced if they withdrew before completing the first cycle for reasons other than toxicitiy. Treatment was continued until there was evidence of disease progression or unacceptable toxicity or the patient decided to discontinue treatment for any reason.

The terameprocol dosing schedule was chosen on the basis of information and advice from Erimos Pharmaceuticals. Terameprocol was infused though a central or peripheral line at 150 mL/hour using a terameprocol-compatible infusion system provided by Erimos Pharmaceuticals. Antiemetics were not administered, and anticonvulsants and corticosteroids were administered as clinically indicated. If a patient developed a DLT, a subsequent dose of terameprocol could be administered after resolution of the toxicity by lowering the dose to the previous dose level. Tetra-O-methyl NDGA (M4N) is a semi-synthetic derivative of NDGA also known as terameprocol (TMP). Because terameprocol is poorly soluble in water, it was formulated for intravenous administration as a 10 mg/mL solution in a vehicle composed of PEG 300, hydroxypropyl-β-cyclodextrin, and water for intravenous administration (designated as CPE). An area of 2 cm2 skin was tape-stripped using an autoclave tape after removal of the fur on the mouse back.

As a result, during the conduct of this study, the formulation was changed to eliminate PEG. LPS from Salmonella Minnesota R595 was purchased from LIST Biological Laboratories, Inc. It’s also important that they take a lot of probiotics, anywhere from 50-100 billion microorganisms per day. Blood samples for characterizing terameprocol pharmacokinetics were obtained from a peripheral vein before administration and at the following times after starting the first daily infusion: 0.25, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 6.0, and 24 h. Blood was collected in tubes without an anticoagulant and permitted to clot for approximately30 min before centrifuging (1200–1500 × g, 15 min, 4°C). Chaparral may also interact with cancer, antiviral, gastrointestinal, immunosuppressant, thyroid, and abortion-inducing drugs. Seemingly miraculous cures were obtained by indigenous coastal individuals methodically self-medicating with Oplopanax tea.

Heavy metal toxicity causes neurological symptoms, fatigue, muscle/ joint pain, cognitive deficits and many other symptoms in common with Lyme disease. Chaparral may increase the risk of high blood pressure if used with other herbs with this effect. Tumor response and progression were categorized using the Macdonald criteria.24 Patients were defined as having progressive disease if there were (1) new lesions on serial neuroimaging studies, (2) >25% increase in the bidirectional measurement of contrast-enhancing tumor on MRI or CT, or (3) progressive neurologic abnormalities that could not be attributed to etiologies other than tumor progression. Overall survival was assessed using the Kaplan-Meier method.25 Patients who had not died prior to data cutoff were censored at the last date on which they were known to be alive. A total of 35 patients participated in to this research study during 2007–2008. Sixteen (46%) of these patients were male, 32 were white, 2 were African American, and 1 was Asian. They had a median age of 46 years (range, 29–71 years) and a median Karnofsky performance status of 80 (range, 60–100) and had received a median of 2 prior chemotherapy regimens (range, 1–6).

The last documented histologic diagnosis was glioblastoma in 15 patients (43%), anaplastic oligodendroglioma in 11 patients (31%), and anaplastic astrocytoma in 9 patients (26%). A summary of the total number of patients treated and the number of observed DLTs as a function of dose, formulation, and EIASD administration is presented in Table . A summary of observed toxicities is provided in Table . A total of 18 patients participated in the −EIASD cohort. Three patients were treated at doses of 750, 1100, and 1700 mg/day without DLT for 2, 3, and 23 months; 1, 2, and 10 months; and 2, 2, and 4 months, respectively. At 2200 mg, 1 of 3 patients developed a grade 3 ileus, and thus, another 3 patients were added to the cohort. One of these developed grade 3 dyspnea.

These patients were treated for 1, 1, 1, 2, 2, and 4 months. Because 2 of 6 patients at the 2200 mg dose level had DLTs, the MTD with the PEG formulation was determined to be 1700 mg/day. After reformulation to a PEG-free infusion, 3 additional patients were treated at 1700 mg without DLTs for 2, 2, and 6 months. Essential oils provide natural fragrance, healing properties, and natural preservative properties to your products. These patients were receiving phenytoin (10), carbamazepine (3), and oxcarbazepine (1). No DLTs were seen in 3 patients treated at 750 mg/day. These patients received 1, 2, and 8 months of treatment before developing progressive disease.

Four patients were treated at a dose of 1100 mg/day, because 1 of the first 3 patients accrued was inevaluable for the toxicity evaluation and was replaced. No DLTs were observed, and they were treated for 1, 1, and 10 months before developing progressive disease. Three patients were treated at 1700 mg/day, and 2 were treated at 2200 mg/day without DLTs. These patients received 1, 2, and 8 months of treatment before developing progressive disease. No. “The nerves are like a network of electrical wires in a city. With the new PEG-free formulation, the regimen was reinstituted at 1 dose level below the prior dose.

1, 1995), incorporated herein by reference. A planned interim analysis of the pharmacokinetic data suggested that the concurrent EIASD administration did not significantly affect the pharmacokinetics of terameprocol. As a result, subsequent patients were enrolled in a combined cohort without regard for EIASD use. Two of the 3 patients accrued to the 2200-mg dose using the new formulation developed DLTs (grade 4 hypoxia and grade 2 interstitial nephritis) after 1 or 2 doses, and the third patient developed progressive disease after 2 months. As a result, the study was closed, with the recommended dose of the PEG-free formulation being 1700 mg per day for 5 consecutive days each month. Serum concentration-time data that were amenable to pharmacokinetic analysis for the initial daily dose of terameprocol were available for 9 patients in the +EIASD treatment group and 16 patients in ­EIASD group. The mean and standard deviation for the total body clearance, steady-state apparent volume of distribution, and terminal phase half-life of the drug in the 2 treatment groups are presented in Table .

There were no differences between any of these parameters that approached statistical significance, suggesting that the concurrent administration of EIASD does not have a clinically significant effect on the serum pharmacokinetics of terameprocol.

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