estramustine and Edema

To exploit the favorable dose intensity and safety profile of weekly paclitaxel, we conducted a Phase I trial of paclitaxel by 3-hour infusion in combination with estramustine phosphate (EM) in men with hormone-refractory prostate cancer (HRPC). The antimicrotubule drug combination of paclitaxel by 96-hour infusion plus EM is active in HRPC.. Twenty-four patients with metastatic HRPC and progressive tumor after antiandrogen withdrawal were enrolled in this study. Oral EM was taken at a dose of 600 mg/m(2) daily for the initial 21 patients and on a reduced schedule of 280 mg twice daily for the final 3 patients. Paclitaxel was escalated from 60 to 118 mg/m(2).. The major toxicities were gastrointestinal and thromboembolic complications related to daily oral dosing of EM. Of the first 21 patients, one third (n = 7) discontinued therapy within 4 weeks because of protracted nausea and/or thrombotic complications. Dose-limiting toxicities at 118 mg/m(2) paclitaxel were fatigue and hepatotoxicity. Of 13 patients with measurable soft-tissue lesions, 6 had objective partial regressions, and 9 (37.5%) of 24 patients (95% confidence interval 19.1% to 59.1%) with elevated prostate-specific antigen levels had a 50% or greater decline of at least 4 weeks' duration.. Weekly paclitaxel at doses of 60 to 107 mg/m(2) were feasible in combination with oral EM, but daily oral EM produced unacceptable toxicity. On the basis of these results, a Phase II trial of weekly paclitaxel with the reduced dose and schedule of EM was initiated by the Eastern Cooperative Oncology Group to assess further the benefits and risks of this treatment in men with metastatic HRPC.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Anaphylaxis; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Disease Progression; Disease-Free Survival; Drug Resistance, Neoplasm; Edema; Estramustine; Gonadotropin-Releasing Hormone; Humans; Infusions, Intravenous; Male; Middle Aged; Nausea; Paclitaxel; Prostatic Neoplasms; Thrombophlebitis; Treatment Outcome

To investigate the influence of single nucleotide polymorphisms (SNP) on transcription of the 17beta-hydroxysteroid dehydrogenase (HSD17B7) gene.. Luciferase reporter genes containing a 5'-flanking of the HSD17B7 gene, as well as the sequence around the SNP, were transfected into LNCaP and DU145 cells. Then, luciferase assays were carried out.. The presence of the G allele resulted in an increase of transcriptional activity derived from the 5'-flanking region of the HSD17B7 gene by 270% and 370% in LNCaP and DU145 cells, respectively. Transcriptional activity of the HSD17B7 gene containing the G allele was higher than that of the C allele.. The transcriptional activity of the HSD17B7 gene containing the G allele is higher than that of the C allele. This difference in HSD17B7 expression may regulate the risk of peripheral edema as an adverse reaction induced by estramustine phosphate sodium.

Topics: 17-Hydroxysteroid Dehydrogenases; Antineoplastic Agents, Hormonal; Edema; Estramustine; Humans; Polymorphism, Single Nucleotide; Transcription, Genetic; Tumor Cells, Cultured

Estramustine phosphate sodium (EMP) frequently causes side-effects such as gastrointestinal discomfort, nausea, and edema in extremities. We analyzed single nucleotide polymorphisms (SNP) in the 17beta-hydroxysteroid dehydrogenase (HSD17B) genes, which are involved in the metabolism of EMP, to predict the risk of EMP side-effects in prostate cancer patients.. We performed genotyping of SNP in the HSD17B genes of 44 Japanese patients with newly diagnosed prostate cancer. The association of SNP and individual EMP side-effects was evaluated.. Peripheral edema occurred more frequently in patients with C/C genotype of IMS-JST123219 than in those with C/G genotype (OR: 5.47, 95% CI: 1.27-23.64). Haplotype analysis showed that appetite loss was associated with the G allele of IMS-JST123219 and the T allele of IMS-JST123218 (OR: 9.13, 95% CI: 1.15-72.76).. These preliminary data demonstrated that analyses of SNP in the HSD17B genes might predict the occurrence of side-effects from EMP.

Topics: 17-Hydroxysteroid Dehydrogenases; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Appetite; Edema; Estramustine; Gene Frequency; Genotype; Haplotypes; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Risk Factors