Oncology reports
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Although many prostate cancer cases relapse to a hormone-insensitive state, endocrine therapy involving androgen depletion by orchiectomy or by treatment with LHRH-analogue as well as blockade of the androgen receptor (AR) with anti-androgens remains a primary treatment option. Quality of life (QOL) however, is a prime consideration of men choosing such an approach. In this report we discuss a synergistic combination of 150-mg bicaltumide (Casodex) and 5 mg finasteride (Proscar) in the treatment of a 69-year-old patient with a relapsed (biochemical failure) Gleason score 7 prostate cancer, initially treated with external beam radiation therapy. ⋯ Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that the combination of bicaltumide-finasteride at the same ratio as used clinically, produced synergistic effects on the inhibition of cell proliferation and AR expression/phosphorylation. A more complete inactivation of the AR on this regimen may have had the effect of constraining the ability of the AR to mutate, and/or diminishing the ability of androgen independent clones to evolve. Thus, passage to androgen independence may have been slowed or arrested.
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We conducted a clinical pharmacological evaluation of paclitaxel/carboplatin combination in Japanese patients with non-small cell lung cancer. The purpose of this study was to identify the optimal dose of this combination and to investigate the relationships between the pharmacokinetic profiles of these 2 drugs, serum thrombopoietin (TPO) kinetics and the platelet-sparing effect. Patients received paclitaxel at 180-225 mg/m(2) by intravenous infusion over 3 h, followed by carboplatin at a target area under the concentration-time curve (AUC) of 6 mg/ml x min as a 1-h infusion. ⋯ The early increase in TPO (the percentage increase in TPO at day 4) was significantly greater (p=0.0345) in patients treated with paclitaxel/carboplatin combination (57.8+/-44.5%) compared with single-agent carboplatin (21.3+/-34.1%). The recommended doses are paclitaxel 210 mg/m(2) and carboplatin at an AUC of 6 mg/ml x min every 3 weeks. The observed platelet-sparing effect of the paclitaxel/carboplatin might be related to the early increase in circulating TPO levels, although the precise mechanism remains to be elucidated.