Phase I Clinical Study of the Dietary Supplement, Agaricus blazei Murill, in Cancer Patients in Remission

Although many cancer patients use complementary and alternative medicine, including Agaricus blazei Murill (ABM), safety is not yet well understood. Cancer survivors took 1.8, 3.6, or 5.4 g ABM granulated powder (Kyowa Wellness Co., Ltd., Tokyo, Japan) per day orally for 6 months. Adverse events were defined by subjective/objective symptoms and laboratory data according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTCAE v3.0). Seventy-eight patients were assessed for safety of ABM (30/24/24 subjects at 1/2/3 packs per day, resp.). Adverse events were observed in 9 patients (12%). Most were digestive in nature such as nausea and diarrhea, and one patient developed a liver dysfunction-related food allergy, drug lymphocyte product. However, none of these adverse events occurred in a dose-dependent manner. This study shows that ABM does not cause problems in most patients within laboratory parameters at the dosages tested over 6 months. This trial supports previous evidence that the ABM product is generally safe, excluding possible allergic reaction

Prevention of the initial testosterone surge induced by a luteinizing hormone-releasing hormone analogue in prostate cancer patients:the endocrinological effects of pretreatment with chlormadinone acetate

We investigated the endocrinological effects of pretreatment with chlormadinone acetate (CMA) in preventing the initial testosterone surge induced by a luteinizing hormone-releasing hormone (LH-RH) analogue. A total of 25 patients with previously untreated prostate cancer were included in this study. The patients were randomly assigned to 2 treatment groups:Group1;CMA therapy was begun 4 weeks before the initial LH-RH analogue injection. Group 2;CMA therapy was begun 2 weeks before the initial LH-RH analogue injection. After the initial LH-RH analogue injection, CMA was administered during this study. After LH-RH analogue application, the mean values of serum luteinizing hormone (LH) and testosterone increased in both groups on day 3. However, LH and testosterone levels remained beneath pretreatment values in both groups. The mean relative PSA levels did not significantly increased on day 3 and day 7in both groups. Our results indicate that pretreatment with CMA for 2 weeks was sufficient to prevent the initial testosterone surge in the maximal androgen blockade which was associated with CMA

ホルモン抵抗性前立腺癌に対するドセタキセル, プレドニゾロン併用療法

Between April 2004 and August 2005, we used docetaxel in combination with prednisolone to treat 14 patients with hormone-refractory prostate cancer (HRPC). Docetaxel was administered at a dose of 70 mg/m2 once every 21 days and oral prednisolone 5 mg was administered twice daily concurrently on days 1-21. The treatment was continued until disease progression or unacceptable adverse events occurred. Prostate specific antigen (PSA) was used as a tumor marker. PSA response was defined as a reduction from baseline of at least 50% that was maintained for 4 weeks. Five patients had measurable soft tissue lesions, which were nodal metastases in 4 and liver metastasis in 1. The median follow-up was 8.4 months. During follow-up, 5 patients died. The median treatment cycle was 7 cycles. Manifestations of hematologic toxicity included 11 patients (78%) with grade 3/4 neutropenia and only I with febrile neutropenia. Two patients with gastric hemorrhage and febrile neutropenia needed hospitalization. During follow-up, 8 patients (57%) achieved a PSA reduction from baseline of at least 50%. Three patients with nodal metastases and 1 patient with liver metastasis had partial response. Combined docetaxel and prednisolone was shown to be effective and feasible in Japanese patients.【目的】ホルモン抵抗性前立腺癌に対しドセタキセル+プレドニゾロン療法を行い, その有用性を検討した。【対象・方法】対象は2004年4月以降に再燃前立腺癌と診断された14例。観察期間は8.4ヵ月, 7コース(5.5コース)施行した。プレドニゾロン(10mg/日)連日投与を併用しドセタキセル70mg/m2を21日毎に点滴投与を繰り返した。全例, 転移巣を有しており, 測定可能病変は4例がリンパ節, 1例は肝臓であった。原則として外来通院治療とした。【結果】14例中8例(57%)で腫瘍マーカーが50%以上減少した。測定可能病変とでは肝臓の1例とリンパ節の2例がPRとなった。鎮痛剤を使用していた7例中4例が減量・中止可能であった。貧血が2例で改善し, 1例で発熱も改善した。血液有害事象では好中球減少ではgrade3/4が11例であった。PDのため4例, 高度の皮膚粘膜病変のため1例が中止し, ステロイドによる出血性胃潰瘍, 帯状疱疹のため1例ずつが休薬となった。発熱性好中球減少のため1例が入院を要した。【結語】好中球減少症を高頻度に認めるが外来治療が可能であり, また抗腫瘍効果, 疼痛の改善においても有用と思われた。(著者抄録

ホルモン抵抗性前立腺癌に対するリン酸エストラムスチン, エトポシド療法

A total of 42 patients with hormone-refractory prostate cancer received E-E therapy. Oral estramustine phosphate (EMP) was administered twice daily for a total daily dose of 560 mg every day and oral etoposide (E-E therapy, 50 mg/body/day) was given on days 1-21 and stopped on days 22-35. Treatment was continued until the disease progression was confirmed radiographically or PSA had increased from base line of at least 25%. The median follow-up period after E-E therapy was 77.4 months (range : 12.5 to 122.3). Nineteen patients (43%) achieved a PSA decrease of 50% or greater. The median survival time of the patients who had a decrease of 50% or greater in the PSA value (PSA responder) was 29.3 months and the patients who did not (PSA non-responder) was 14.1 months (p = 0.01). There were no significant differences between PSA responders and non-responders when taking into account variables. Excluding those patients with only PSA elevation, the survival time was 14.9 months with no significant difference between PSA responders and non-responders. The toxicities (grade 3 or more) were identified as anemia, leukocytopenia thrombocytopenia, cardiovascular events, and gastrointestinal and hepatic disorders, which occurred in 0, 5, 2, 2, 14, and 2% of the patients, respectively. E-E therapy was considered to be an active oral regimen and well-tolerated for outpatients with hormone-refractory prostate cancer in Japanese patients.【目的】日本人における再燃前立腺癌に対する経口リン酸エストラムスチン(EMP), エトポシド(VP-16)併用療法(EE療法)の効果および副作用について検討した。【方法】1995年以降, EE療法が施行された再燃前立腺癌患者42例が対象。EMP:560mgを連日投与, VP-16:50mgを21日投与し14日休薬を1サイクルとした。PSAが50%以上低下したものをresponderとし, 治療は画像上の増悪またはPSAが基準値より25%を認めるまで継続した。【結果】観察期間は77.4ヵ月。19例がresponderであった。42例の生存中央値は20.5ヵ月でありresponderでは29.3ヵ月, non-responderで14.1ヵ月(p=0.008)であった。群間でresponseに寄与する因子は存在しなかった。Grade 3以上の副作用は白血球減少(5%)が2例, 血小板減少(2%)が1例, 悪心が6例(14%), 肝機能障害が1例(2%), 深部静脈血栓症(2%)が1例に認めた。【結語】EE療法は抗腫瘍効果もあり, 副作用も容認でき日本人にも施行可能であった。(著者抄録