Biomedical subjects

Mary Louise Keohan

Publications and source records attributed to Mary Louise Keohan.

3 recordsLinked to original sources

PubMed2006

Phase II study of intravenous TZT-1027 in patients with advanced or metastatic soft-tissue sarcomas with prior exposure to anthracycline-based chemotherapy.

BACKGROUND: TZT-1027, a novel chemotherapeutic agent, is derived from dolastatin 10, and blocks cells during G2/M-phase by interfering with microtubule assembly and stability. TZT-1027 has exhibited potential cytotoxic activity in several human cancer cell lines (in vitro) and also demonstrated antitumor activity in human xenografts (in vivo). In addition, Phase I clinical investigations suggested activity in STS (soft-tissue sarcoma). METHODS: Eligible patients were those who had histologic evidence of locally advanced or metastatic STS and who had received 1 prior treatment regimen with an anthracycline-based chemotherapy for metastatic disease. Subjects received intravenous infusions of TZT-1027 over 1 hour on Day 1 and Day 8 of each 21-day treatment course. Efficacy was evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Twenty-nine patients were enrolled and 28 patients received at least 1 course of study drug and were eligible for efficacy and safety evaluation. The median age of the patients was 48 years (range, 23-73 years) and the median baseline Eastern Cooperative Oncology Group (ECOG) performance status was 1 (range, 0-2). A total of 67 courses (range, 1-9 courses; median, 2 courses) of TZT-1027 were administered. No patient in the study demonstrated an objective response to treatment. Of 6 patients (21.4%) who experienced disease stabilization, 1 continued to have stable disease for 9.3 months. The median time to tumor progression was 44 days (95% confidence interval [95% CI], 43.0-54.0) and the median survival was 178 days (95% CI, 134.0-317.0). The most commonly reported toxicities were neutropenia, fatigue, and constipation. CONCLUSIONS: TZT-1027 was found to be safe and well tolerated, and the hematologic toxicities observed were consistent with preclinical toxicology and Phase I study findings. No confirmed responses were seen in the current study.

Adult↗

PubMed2003

A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma.

BACKGROUND: The objective of this study was to assess the efficacy and toxicity of the imidazotetrazine derivative temozolomide for patients with unresectable or metastatic soft tissue sarcoma. METHODS: Twenty-five of 26 patients were eligible and assessable for toxicity and response. Temozolomide was administered twice daily on a 12-hour schedule for 5 days as an oral bolus dose of 200 mg/m(2) followed by 9 doses of 90 mg/m(2) every 4 weeks. RESULTS: There were 2 partial responses, 2 mixed responses, and 3 patients with stable disease that lasted > 6 months, for an overall objective response rate of 8%. At a median follow-up of 13.2 months, the median progression-free survival and the median overall survival were 2.0 months (95% confidence interval [95% CI], 1.7-2.3) and 13.2 months (95% CI, 4.7-31.1), respectively. All responding patients had leiomyosarcoma of uterine or nonuterine origin; and, in a subset analysis of these patients, the objective response rate was 18% (2 of 11 patients), with disease stabilization occurring in 3 of 11 patients (27%). For this subgroup, at a median follow-up of 24.4 months, the median progression-free survival and the median overall survival were 3.9 months (95% CI, 1.9-21.9) and 30.8 months (lower-bound 95% CI, 7.8), respectively. There were no treatment-related deaths or National Cancer Institute Grade 4 toxicities. Grade 3 toxicities included nausea, anemia, fatigue, elevated alkaline phosphatase levels and nonneutropenic fever (1 patient each). CONCLUSIONS: Temozolomide at the dose schedule employed in the current study was tolerated well and had modest activity against previously treated unresectable or metastatic leiomyosarcoma of both uterine and nonuterine origin.

Adult↗

PubMed2003

Factor analysis validates the cluster structure of the dendrogram underlying the Multidimensional Affect and Pain Survey (MAPS) and challenges the a priori classification of the descriptors in the McGill Pain Questionnaire (MPQ).

The purpose of this study was to validate the content and structure of the Multidimensional Affect and Pain Survey (MAPS) by means of factor analysis. The 101-MAPS is based on a dendrogram obtained by cluster analysis and contains 30 clusters subsumed within three superclusters. If the MAPS is a valid questionnaire for the quantification of emotion and pain in patients, then factor analysis of patients' intensity ratings should produce factors which correspond to the cluster structure of the dendrogram. To confirm the structure of the dendrogram and hence, MAPS, factor analysis was applied to the responses by 100 outpatients diagnosed with early stage cancer. Principal components analysis of responses to the MAPS yielded six factors. In accordance with the hypothesis, 13 of the 17 clusters within the MAPS somatosensory pain supercluster loaded on three sensory factors: factor 1, severe sensory pain; factor 3, moderate sensory pain; and factor 6, numb/cold. Five of the eight clusters within the emotional pain supercluster loaded on factor 2, negative emotions. Four of the five clusters in the well-being supercluster loaded on factor 4, good health. Factor 5, manageable illness was loaded on by clusters from the well-being supercluster and the somatosensory pain supercluster. The homogeneity of the six factors found demonstrate the validity of the MAPS and the cluster structure of the dendrogram. MAPS proved sensitive to sex differences; women endorsed the negative emotions factor more strongly than did men. The MAPS factors were much more homogeneous than those reported in the literature for the McGill Pain Questionnaire.

Adult↗