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Biomedical subjects

G Hudes

Publications and source records attributed to G Hudes.

6 recordsLinked to original sources
PubMed1997

Estramustine-based chemotherapy.

Long misclassified as an alkylating agent, estramustine phosphate is a stable conjugate of estradiol and nornitrogen mustard with antimitotic properties. Binding of the drug to microtubule-associated proteins, tubulin, and proteins of the nuclear matrix are presently considered to be the most likely mechanisms underlying the cytotoxicity of estramustine in androgen-independent prostatic carcinoma. Identification of these mechanisms of action has led to clinical reevaluation of estramustine phosphate (EMP) in several rationally designed drug combinations. Combination of EMP with either vinblastine, paclitaxel or etoposide has produced antitumor responses in 30% to 60% of patients with metastatic hormone-refractory prostate carcinoma as determined by reduction in bidimensionally measurable soft tissue disease, pain, and serum prostate-specific antigen. Whereas the antitumor activity of the combinations has been greater than additive for the single agents, the toxicities of treatment have not been greater than predicted for the individual drugs. The promising results of EMP-based chemotherapy encourage additional laboratory and clinical investigations to develop more effective therapy for hormone-refractory disease and for selected patients with earlier stages of prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed1996

Patterns-of-failure analysis of patients with high pretreatment prostate-specific antigen levels treated by radiation therapy: the need for improved systemic and locoregional treatment.

PURPOSE: The patterns of failure (local and/or regional v metastatic) have been determined for patients with prostate cancer and pretreatment prostate-specific antigen (PSA) levels > or = 20 ng/mL treated with radiation alone with the purpose to design appropriate multimodal treatments. MATERIALS AND METHODS: One hundred twenty patients with pretreatment PSA levels > or = 20 ng/mL were treated with external-beam radiation alone between February 1988 and October 1993. They were arbitrarily divided by PSA levels, 20 to 29.9 ng/mL, 30 to 49.9 ng/mL, and > or = 50 ng/mL, and analyzed in terms of freedom from any failure (no evidence of biochemical disease [bNED], and PSA level < 1.5 ngm/mL and not increasing), as well as freedom from imaging evidence of distant metastasis (fdm). RESULTS: There was no significant difference in short-term outcome by pretreatment PSA level, and thus all patients were pooled for analysis. At 4 years, 81% were fdm and 28% were free of any failure. This suggests that approximately 50% have recurred with local and/or regional disease or undetectable metastatic disease. Multivariate analysis indicated that low palpation stage and higher center of prostate dose were associated with better bNED survival. Multivariate analysis indicated that increasing stage and younger age are significantly associated with increasing distant metastasis. CONCLUSION: Patients with pretreatment PSA levels > or = 20 ng/mL are not optimally treated by irradiation alone. The pattern of failure suggests improvement may come from systemic treatment of metastatic disease and high-dose radiation to improve locoregional disease. To evaluate this, we have begun a multimodal trial of chemohormonal therapy followed by extended-field irradiation.

Analysis of Variance↗
PubMed1995

Prostate specific antigen density is not an independent predictor of response for prostate cancer treated by conformal radiotherapy.

Although prostate specific antigen (PSA) density appears to be an important discriminator between benign and malignant prostatic disease, conflicting data exist concerning its prognostic value. The present study was undertaken to confirm whether PSA density represents a new prognostic indicator of disease-free survival for prostate cancer treated with conformal radio-therapy. Between April 1989 and December 1992, 186 patients with organ confined prostate cancer were treated with definitive irradiation according to previously published conformal guidelines. The PSA density was defined as the ratio of the pretreatment serum PSA (ng./ml.) to the prostate volume (ml.) as determined from treatment planning computerized tomography. The median PSA density was 0.15 with a range of 0.02 to 2.12. A statistically significant advantage in actuarial freedom from biochemical relapse was noted for patients with pretreatment PSA levels less than 15 ng./ml. when compared to those with higher pretreatment PSA levels (3-year freedom from biochemical relapse 85% versus 28%, p < 0.001). Also, patients with PSA density of 0.15 or less had statistically superior freedom from biochemical relapse compared to their counterparts with higher PSA density (3-year freedom from biochemical relapse 88% versus 28%, p < 0.001). In a multivariate analysis only the baseline PSA (p < 0.002) and the Gleason score (p < 0.002) emerged as significant predictors of prolonged freedom from biochemical relapse. The PSA density had no impact on freedom from biochemical relapse whether it was entered into this multivariate model as a continuous or a dichotomous variable. In our data base baseline PSA levels remain the most powerful independent discriminant of response to conformal irradiation. PSA density is only a surrogate for baseline PSA levels and does not refine the ability to predict prolongation of freedom from biochemical relapse following conformal radiotherapy.

Actuarial Analysis↗
PubMed1992

Preclinical and clinical perspectives on the use of estramustine as an antimitotic drug.

A variety of cell biological, pharmacological, crystallographic and clinical approaches have indicated that the antimitotic drug estramustine has interesting and unusual properties. Although designed as an alkylating agent, the marked stability of the carbamate linkage to the steroid carrier molecule prevents the formation of alkylating intermediates. The affinity of the parent molecule for microtubule associated proteins and the concomitant antimicrotubule activity have cytotoxic consequences in tumor cells. Both preclinical and clinical studies of estramustine in combination with other antimicrotubule agents have shown that this approach has great potential to achieve therapeutic advantage, especially in disease states such as hormone refractory prostate cancer.

Animals↗
PubMed1988

Extranodal non-T-cell lymphoblastic lymphoma in adults. A report of two cases.

Typical adult cases of malignant lymphoma, diffuse, lymphoblastic type (MLLB), are of the T-cell immunophenotype and occur as mediastinal masses. The authors report two unusual adult cases with initial extranodal sites of involvement and non-T-cell immunophenotype that were originally misclassified. One patient presented with a right submaxillary salivary gland mass and the other presented with a T7-8 spinal cord compression resulting from a vertebral body tumor. A lymphoblastic leukemic phase developed in both patients after 15 months and 5 months, respectively. The bone marrow blasts of both patients had positive results for cluster designation (CD) 10, CD19, HLA-DR, and terminal deoxynucleotidyl transferase. Because both extranodal sites of presentation and non-T-cell immunophenotype are unusual in adult MLLB, these features may have contributed to the original misclassification of these lesions.

Adult↗