Phase I trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma.
Phase I trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma.
复制标题
每日雌莫司汀磷酸盐联合间歇性多西紫杉醇治疗转移性激素难治性前列腺癌患者的 I 期试验。
DOI：
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发表时间：
1999
影响因子：
50.5
通讯作者：
Vincent Vinciguerra
中科院分区：
文献类型：
--
作者：
Willi Kreis;D. Budman;J. Fetten;A. Gonzales;B. Barile;Vincent Vinciguerra
BACKGROUND
To apply our preclinical findings of cytotoxic synergy with the combination of estramustine phosphate (EP) and docetaxel as the basis of treatment of hormone refractory metastatic prostate cancer in man. To determine the optimal dosage and the toxicities of these two agents for future trials.
PATIENTS AND METHODS
Seventeen patients with hormone refractory metastatic prostate cancer who were ambulatory with performance status < or = 2, normal marrow, renal and hepatic function were entered. Prior exposure to EP or a taxane were exclusion factors. EP was given orally at a dose of 14 mg/kg of body weight daily with concurrent docetaxel administered every 21 days as an intravenous infusion over 1 hour with dexamethasone 8 mg. PO BID for five days. EP dosages were kept static; docetaxel dosages were explored in a minimum of three patients per level for dosages of 40, 60, 70, and 80 mg/m2. Patients were evaluated weekly. Prostate specific antigen (PSA) was measured every three weeks.
RESULTS
Five patients were entered at a docetaxel dose of 40 mg/m2, three at 60 mg/m2, six at 70 mg/m2, and three at 80 mg/m2. Only one patient had received prior chemotherapy. Grades 1 or 2 hypocalcemia and hypophosphatemia were seen at all dosage levels. Other grade 2 or less toxicities not related to dosage included alopecia, anorexia, stomatitis, diarrhea, and epigastric pain. Dose limiting toxicities (DLT) as grade 4 leukopenia and grade 4 fatigue were seen at 80 mg/m2. The phase II dose was defined at 70 mg/m2 with rapidly reversible leukopenia and minor liver function abnormalities. At this dosing level, dose intensity was 88% and 86% over consecutive cycles for docetaxel and EP, respectively. Two vascular events occurred at this dose level (70 mg/m2): one arterial and the other venous. PSA decreases greater than 50% from baseline were seen in 14 of 17 patients at all dosage levels. Four of the 17 patients demonstrated a complete biochemical response (PSA < or = 4 ng/ml). One patient had a partial response with measurable lung and liver lesions.
CONCLUSION
EP given continuously with every three-week docetaxel at a dose of 70 mg/m2 is tolerable with evidence of antitumor activity based upon significant declines in PSA in the majority of patients and improvement of lung metastasis in one patient. Larger phase II studies of this combination in a homogenous population are warranted.
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雌莫司汀通过与微管蛋白结合来解聚微管。
影响因子：
11.2
作者：
Dahllof,B;Billstrom,A;Cabral,F;Hartley-Asp,B
通讯作者：
Hartley-Asp,B
影响因子：
11.2
作者：
L. Speicher;L. Barone;K. Tew
通讯作者：
L. Speicher;L. Barone;K. Tew
由于雌莫司汀耐药，人前列腺癌细胞中 β(III)- 和 β(IVa)-微管蛋白同位素增加。
DOI：
--
发表时间：
1996
期刊：
Cancer research.
影响因子：
--
作者：
Ranganathan,S;Dexter,DW;Benetatos,CA;Chapman,AE;Tew,KD;Hudes,GR
通讯作者：
Hudes,GR
DOI：
10.1093/jnci/83.4.288
发表时间：
1991-02-20
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
RINGEL, I;HORWITZ, SB
通讯作者：
HORWITZ, SB
影响因子：
45.3
作者：
KELLY, WK;SCHER, HI;FOSSA, SD
通讯作者：
FOSSA, SD