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Biomedical subjects

Charles Taylor

Publications and source records attributed to Charles Taylor.

7 recordsLinked to original sources
PubMed2006

A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors.

PURPOSE: HMN-214 is an oral prodrug of HMN-176, a stilbene derivative that interferes with the subcellular spatial location of polo-like kinase-1, a serine/threonine kinase that regulates critical mitotic events. We conducted a dose escalation study of HMN-214 in patients with advanced cancer to assess the safety profile and pharmacokinetics of HMN-214 and to establish the maximum tolerated dose. EXPERIMENTAL DESIGN: Thirty-three patients were enrolled onto four dosing cohorts of HMN-214 from 3 to 9.9 mg/m2/d using a continuous 21-day dosing schedule every 28 days, with pharmacokinetic sampling during cycle 1. RESULTS: A severe myalgia/bone pain syndrome and hyperglycemia were dose-limiting toxicities at 9.9 mg/m2/d. A dose reduction and separate enrollment by pretreatment status (lightly versus heavily pretreated) was undertaken, with one dose-limiting toxicity (grade 3 bone pain) at 8 mg/m2/d. The maximum tolerated dose was defined as 8 mg/m2/d for both treatment cohorts. Dose-proportional increases were observed in AUC but not Cmax. There was no accumulation of HMN-176, the metabolite of HMN-214, with repeated dosing. Seven of 29 patients had stable disease as best tumor response, including 6-month stable disease in a heavily pretreated breast cancer patient. A transient decline in carcinoembryonic antigen in a patient with colorectal cancer was noted. CONCLUSIONS: The maximum tolerated dose and recommended phase II dose of HMN-214 when administered on this schedule was 8 mg/m2/d regardless of pretreatment status. Further development of HMN-214 will focus on patient populations for which high expression of polo-like kinase-1 is seen (i.e., prostate and pancreatic cancer patients).

Administration, Oral↗
PubMed2005

Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer.

PURPOSE: Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and blocks its ability to dimerize with other HER receptors. Pertuzumab represents a new class of targeted therapeutics known as HER dimerization inhibitors. A clinical study was conducted to investigate safety and pharmacokinetics of pertuzumab and to perform a preliminary assessment of HER dimerization inhibition as a treatment strategy. PATIENTS AND METHODS: Patients with incurable, locally advanced, recurrent or metastatic solid tumors that had progressed during or after standard therapy were recruited to a dose-escalation study of pertuzumab (0.5 to 15 mg/kg) given intravenously every 3 weeks. RESULTS: Twenty-one patients received pertuzumab and 19 completed at least two cycles. Pertuzumab was well tolerated. Overall, 365 adverse events were reported and 122 considered to be possibly drug related. Of these, 116 were of grade 1 to 2 intensity. The pharmacokinetics of pertuzumab were similar to other humanized immunoglobulin G antibodies, supporting a 3-week dosing regimen. Trough plasma concentrations were in excess of target concentrations at doses greater than 5 mg/kg. Two patients, one with ovarian cancer (5.0 mg/kg) and one with pancreatic islet cell carcinoma (15.0 mg/kg), achieved a partial response. Responses were documented by Response Evaluation Criteria in Solid Tumors after 1.5 and 6 months of pertuzumab therapy, and lasted for 11 and 10 months, respectively. Stable disease lasting for more than 2.5 months (range, 2.6 to 5.5 months) was observed in six patients. CONCLUSION: These results demonstrate that pertuzumab is well tolerated, has a pharmacokinetic profile which supports 3-week dosing, and is clinically active, suggesting that inhibition of dimerization may be an effective anticancer strategy.

Adult↗
PubMed2005

The incidence and prevalence of type-1 diabetes mellitus.

AIM: To determine the incidence, prevalence of type-1 diabetes mellitus (DM) and the presence of islet-cell antibodies (ICAs) in people of African ancestry in the Bahamas. METHOD: Hospital records of type-1 DM were reviewed. Seventeen consecutive patients had postmeal C-peptide and ICA determined. RESULTS: The incidence and prevalence of type-1 DM in the Bahamas were: incidence--10.1/100,000, age 0-14 years; and prevalence--31/100,000 age 0-24 years. Only two out of 17 (11.8%) patients had ICAs. CONCLUSION: Type-1 DM is common in children of African ancestry in the Bahamas. ICAs were absent in the majority of the patients.

Adolescent↗
PubMed2004

Phase I/II randomized trial evaluating the safety and clinical effects of repifermin administered to reduce mucositis in patients undergoing autologous hematopoietic stem cell transplantation.

PURPOSE: To evaluate the safety of repifermin (keratinocyte growth factor-2) administered before and after autologous hematopoietic stem cell transplantation (auto-HSCT). A preliminary analysis of the ability of keratinocyte growth factor-2 to prevent mucositis was also done. EXPERIMENTAL DESIGN: Forty-two patients received intravenous repifermin (25 microg/kg or 50 microg/kg) or placebo for 3 days before their auto-HSCT conditioning regimen and for up to 10 days after auto-HSCT. Within each dose level, 14 patients were randomized to repifermin and 7 patients to placebo. Clinical evaluations of mucositis were scheduled before auto-HSCT conditioning regimen, on the day of transplant, and three times per week until mucositis resolved. RESULTS: In general, the incidence of adverse events was similar for patients treated with repifermin and placebo. No clinically meaningful differences were noted among treatment groups for clinical laboratory variables. Treatment groups experienced similar time to engraftment. The frequency of Grade 2 to 4 mucositis was 100% for patients in the placebo group, 64% for patients in the 25 microg/kg group (P = 0.041 versus placebo), and 50% for patients in the 50 microg/kg group (P = 0.006 versus placebo). Results of other endpoints, including pain on swallowing and use of pain medication specifically for mucositis, suggested a better outcome for patients in the 50 microg/kg group compared with the placebo and 25 microg/kg groups. CONCLUSIONS: Repifermin was well tolerated. Repifermin given before and after auto-HSCT seems to be active in reducing mucositis, but a larger trial will be necessary to determine the efficacy of repifermin with this dose schedule.

Antineoplastic Agents↗
PubMed2002

Transient hypoglycemic hemiparesis.

Transient hypoglycemic hemiparesis is a rare but important presentation of hypoglycemia that is frequently misdiagnosed as stroke. This is a case of an 18-year-old black female with type 1 diabetes who presented to the emergency department with recurrent acute episodes of hemiparesis that resolved completely after dextrose infusion. It is the intention of the authors to increase awareness of this disorder which, if misdiagnosed, could result in permanent neurological damage. Current theories on the etiology of this disorder are discussed.

Adolescent↗