吉西他滨联合顺铂治疗激素非依赖晚期前列腺癌的临床疗效

目的探讨吉西他滨(健择)+顺铂全身化疗治疗激素非依赖性晚期前列腺癌的临床效果及毒副反应.方法本组18例激素非依赖性晚期前列腺癌患者,全部经去势手术及不同程度的抗雄激素药物治疗,经全身骨扫描证实均有多发性骨转移灶,其中肝脏、双侧肾上腺和颅内转移各1例,血PSA呈逐渐上升趋势.用健择 1 000 mg/m2+NS 100 ml静脉滴注,第1、8天各一次;DDP 100 mg/m2+NS 500ml静脉滴注,第1天用,或者DDP 30 mg+NS 250 ml静脉滴注,第1～5天使用;每28天为一个疗程.结果12例患者的血PSA值降至正常水平(<4ng/l),4例PSA值下降超过50%,2例PSA值变化不明显.化疗前,14例骨转移灶疼痛按VRS分级Ⅰ级5例、Ⅱ级6例、Ⅲ级3例,化疗后分别为Ⅰ级3例、Ⅱ级1例、Ⅲ级0例.多发性颅内转移灶其中最大转移瘤直径由化疗前的3.0 cm缩小至 0.5 cm,化疗后面瘫症状消失.肝脏转移瘤由原来的10.2 cm缩小至3.3 cm.双侧肾上腺多发性转移瘤化疗后总的肿瘤体积缩小三分之二以上.随访2～33个月,平均17.3个月,3例患者死亡,中位生存期16.2个月.疼痛缓解期平均为15.3个月.PSA值降低的稳定期平均为14.2个月.本组病例最常见的毒副反应分别是恶心、呕吐、白细胞减少、血红蛋白降低及血小板减少等,但均在可耐受的范围.结论健择联合顺铂全身化疗治疗激素非依赖性晚期前列腺癌的临床疗效显著,毒副反应可耐受,可作为激素非依赖性晚期前列腺癌的一种辅助治疗方法.     

多西他赛联合泼尼松治疗激素难治性前列腺癌的临床研究

[目的]探讨多西他赛联合泼尼松3周方案治疗激素难治性晚期前列腺癌的临床效果及毒副反应。[方法]12例激素难治性晚期前列腺癌患者接受治疗方案：多西他赛75mg/m^2,d1,静脉滴注;泼尼松5mg,2次／d,d1-21口服;每21d为1个周期。[结果]12例中66．6％（8／12）PSA下降≥50％,为治疗有效;16．7％（2／12）PSA下降〈50％,为病情稳定;16．7％（2／12）PSA持续上升,为治疗无效。有骨痛的9例患者中,55．6％（5/9）骨痛缓解,平均缓解期为14．3个月。多发性颅内转移灶最大转移瘤直径由化疗前的2．5cm缩小至0．5cm．肝脏转移瘤由原来的5．0cm缩小至2．4cm,肺转移灶最大转移瘤直径由化疗前的3．2cm缩小至1．0cm．气促缓解．膀胱转移患者化疗后血尿完全消失。全组最主要的毒副反应为骨髓抑制和呕吐。[结论]多西他赛联合泼尼松3周方案治疗激素难治性前列腺癌有一定疗效,毒性可耐受。     

多西他赛联合沙利度胺治疗激素非依赖性晚期前列腺癌的临床观察

目的：探讨多西他赛联合沙利度胺治疗激素非依赖性晚期前列腺癌的临床效果及毒副反应。方法：12例激素非依赖性晚期前列腺癌患者均用多西他赛75mg／m^2＋0．9％氯化钠注射液250mL静脉滴注，第1天；21天为一疗程。沙利度胺的起始剂量为每天100mg，以后每周增加50mg，直到每天300mg。结果：12例患者中，10例患者的血PSA值降至正常水平（〈4ng／ml），1例PSA值下降超过50％，1例PSA值变化不明显。随访6个月，3例患者死亡，中位生存期14个月。疼痛缓解期平均为16．3个月。本组病例最常见的毒副反应分别是恶心、呕吐、白细胞减少、血红蛋白降低及血小板减少等，但均在可耐受的范围。结论：多西他赛联合沙利度胺化疗治疗激素非依赖性晚期前列腺癌的临床疗效显著，毒副反应可耐受，可作为激素非依赖性晚期前列腺癌的一种有效治疗方法。     

磷酸雌二醇氮芥联合非那雄胺治疗激素难治性前列腺癌疗效观察

目的 观察联合应用磷酸雌二醇氮芥(EMP)和非那雄胺治疗激素难治性前列腺癌的疗效.方法 1999年7月至2006年1月联合应用EMP和非那雄胺治疗激素难治性前列腺癌14例.治疗方案EMP 280 mg,每日2次;非那雄胺5 mg,每日1次,28 d为一疗程,连续应用直至毒副反应无法耐受或治疗失败.疗效判断标准血前列腺癌胚抗原(PSA)下降＞50%且维持1个月以上为有效,软组织转移灶疗效分为痊愈、好转、稳定和进展.结果 14例随访3～24个月,平均13个月.PSA有效率57.1%(8/14),有效患者PSA从治疗前(53.6±42.3)ng/ml下降至治疗后3个月(12.8±9.5)ng/ml,平均有效时间9个月.软组织转移灶好转者3例,转移灶分别从治疗前2.0 cm×2.5 cm、3.5 cm ×4.5 cm、4.5 cm ×4.0 cm缩小为1.0 cm×1.0 cm、2.0 cm×2.5 cm、2.0 cm×3.0 cm,有效持续时间分别为5、9、12个月.结论 联合应用EMP和非那雄胺治疗激素难治性前列腺癌有一定疗效.     

吉西他滨联合氟尿嘧啶治疗晚期肝外胆管癌

目的：观察吉西他滨(健择)联台氟尿嘧啶治疗晚期肝外胆管癌的近期疗欢。方法：21例晚期胆管癌患者采用GLF方案化疗：健择1000mg/m^2，静脉滴注30-60分钟，第1，8天给药。亚叶酸钙200mg/m^2，静脉滴注．第1～5天。氟尿啼啶600mg/m^2。静脉滴注2小时．第1～5天。21天为一个两期。结果：21例中无1例达完全缓解，部分缓解5例(23．8％)．稳定8例(381％)。12例(57．14％)患者疼痛得到缓解．生活质量提高。结论：健择联合氟尿嘧啶冶疗晚期无法手术的肝外胆管癌具有较好的近期疗效且不良反应可以耐受。     

吉西他滨治疗晚期恶性实体瘤的疗效观察

目的：观察以吉西他滨（健择，gemcitabine)为主的联合化疗方案地晚期实体瘤的近期疗效，毒副反应。方法：30例晚期恶性实体瘤患者中，初治22例，复治8例，肺癌、乳腺癌用健择加顺铂方案；胰腺癌用健择加LF方案；肝癌肺转移用健择加羟基喜树碱，每例化疗持续2周期以上。共68个周期治疗。结果：30例化疗患者有效率（RR）达46.7%，稳定（SD）者占46.7%，进展（PD)6.7%。毒副反应Ⅲ-Ⅳ度白细胞减少者为20.6,Ⅲ-Ⅳ度血小板减少者为29.4,Ⅲ-Ⅳ度血红蛋白降低教养为8.8%，因素副反应而周期内延期14次（20.6%)，但整个化疗方案仍得以顺利实施，其他毒副反应不影响化疗方案的进行，结论：健择是治疗晚期恶性实体瘤较为安全可靠的抗癌药物之一，毒副反应轻微，易微受，疗效满意，值得进一步研究和推广使用。     

以健择为主介入治疗联合化疗治疗晚期胰腺癌20例

目的探讨以健择为主介入治疗联合全身化疗治疗晚期胰腺癌的疗效。方法在X光监视下将导管插入十二指肠上下动脉,将健择1000mg／m^2以0．9％氯化钠溶液（NS）溶解后每次注入1/2量,氟脲苷（FUDR）0．5g、顺铂（DDP）60mg同样以0．9％氯化钠溶液（NS）溶解后每次靶动脉注入1／2量,d2～d5予全身联合化疗,28d为1周期,完成3个周期评价疗效。结果全组无CR病例,PR11例（55％）,NC6例（30％）,总有效率为55％。结论健择为主介入治疗联合全身化疗治疗晚期胰腺癌有较好的疗效,同时能减轻症状,提高病人的生存质量,但确切疗效有待扩大样本进一步探讨。     

吉西他滨治疗晚期恶性实体瘤的疗效观察

目的 :观察以吉西他滨 (健择 ,gemcitabine)为主的联合化疗方案对晚期实体瘤的近期疗效、毒副反应。方法 :30例晚期恶性实体瘤患者中 ,初治 2 2例 ,复治 8例。肺癌、乳腺癌用健择加顺铂方案 ;胰腺癌用健择加LF方案 ;肝癌肺转移用健择加羟基喜树碱。每例化疗持续 2周期以上 ,共 68个周期治疗。结果 :30例化疗患者有效率 (RR)达 4 6.7% ,稳定 (SD)者占 4 6.7% ,进展 (PD) 6.7%。毒副反应Ⅲ～Ⅳ度白细胞减少者为 2 0 .6% ,Ⅲ～Ⅳ度血小板减少者为 2 9.4 % ,Ⅲ～Ⅳ度血红蛋白降低者为8 8%。因毒副反应而周期内延期 14次 (2 0 .6% ) ,但整个化疗方案仍得以顺利实施。其他毒副反应不影响化疗方案的进行。结论 :健择是治疗晚期恶性实体瘤较为安全可靠的抗癌药物之一 ,毒副反应轻微 ,易耐受 ,疗效满意 ,值得进一步研究和推广使用     

健择联合顺铂方案治疗晚期胰腺癌的疗效观察

目的 :观察GP (健择 DDP)方案治疗晚期胰腺癌的近期疗效与不良反应。方法 :将 2 0例晚期胰腺癌给予GP方案化疗 2个周期 ,按WHO标准评定疗效和不良反应。结果 :有效率 (CR PR)为35 % ,不良反应主要为骨髓抑制和胃肠道反应。结论 :健择加顺铂是治疗晚期胰腺癌的一种安全有效的化疗方案。     

健择联合顺铂每周用药治疗晚期非小细胞肺癌的临床观察

目的:评价健择联合顺铂每周用药治疗晚期非小细胞肺癌的疗效和毒性反应.方法:37例晚期非小细胞肺癌患者应用联合方案化疗,健择1000mg/m2,静滴半小时,第1、8天;DDP 50mg/m2,静滴,第1、8天.结果:37例中,CR 1例,PR 15例,CR+PR 16例,总有效率为43.2%.主要不良反应为白细胞及血小板减少,绝大部分病人均能耐受.结论:健择联合顺铂每周用药方案对晚期非小细胞肺癌有较好疗效,不良反应可以耐受.     

Low-dose cisplatin and UFT for hormone refractory prostate cancer

OBJECTIVES: Biochemical modulation (BM) was initially used to enhance the effect of 5-fluorouracil (5-FU) by modulating its pharmacological action with the addition of other drugs. BM with low-dose cisplatin and 5-FU or UFT has been examined in cases of advanced gastric or pancreas cancer and 30 to 40% response rates have been reported. In the present study, the effect of BM on hormone refractory prostate cancer (HRPC) patients was examined. METHODS: BM consisting of 5 mg/body of cisplatin 3 times per week and 300-450 mg of UFT/day was given to 30 HRPC patients (median and range of age: 66 and 52-72, respectively). The ECOG performance status was 0 to 1. Gleason score was 7 in 8 patients, 8 in 10 patients and 9 in 12 patients, respectively. The metastatic site was bone in 29 patients (extent of disease on bone scan [EOD] grade 1: 10, 2: 10, 3: 8, 4: 1), lymph node in 8 and liver in 1. RESULTS: Among the 29 patients assessable for bone metastasis, 5 (17%) obtained marked improvement on bone scan. One was EOD grade 4 (super bone scan) and 4 were EOD grade 1-3. Eight (28%) were stable and 16 (55%) progressed on bone scan. Among 8 patients with lymph node metastasis, 4 (50%) showed partial response and 4 (50%) progression. One patient with liver metastasis showed complete response. Fourteen (47%) out of 30 patients showed a PSA decline of 50% or greater. Their median response duration was 8 months (range; 2 to 44 months). Among the 25 patients assessable for bone pain, 7 (28%) improved, 12 (48%) remained stable and 6 (24%) progressed. A side effect of Grade II anemia was seen in one patient. CONCLUSION: BM is effective in almost half of hormone refractory prostate cancer patients.     

Chemo-endocrine therapy with low-dose cisplatin, UFT, and dexamethasone for hormone-refractory prostate cancer patients

Since September 2005, twenty-two patients with hormone-refractory prostate cancer (aged 55-81 years) were treated with LH-RH agonist and low-dose cisplatin, UFT, and dexamethasone after proving resistant to estramustine phosphate therapy. The regimen of this therapy consists of 5 mg/body of cisplatin intravenously once a week, 300 mg/day of UFT and 1 mg/day of dexamethasone orally, every day. All patients suffered from clinical progression such as local recurrence in 11 patients who had already received radiation therapy, lymph node metastasis in 7 patients, and bone metastasis in 15 patients. Initial PSA value ranged from 1.7 ng/mL to 215.1 ng/mL. The PSA response rate, which decreased more than 50% in PSA values was 72. 7% (16/22). The follow-up term ranged from 2 to 43 months, and nine patients died of cancer progression. The median time to progression was 11 months, and median overall survival was 19 months. There were no severe adverse effects, and stoppages of the therapy for 13 patients were all due to disease progression. Following this therapy, 9 patients received best supportive care and 4 patients received docetaxel chemotherapy. We considered this therapy to be effective for patients with hormone-refractory prostate cancer because it maintained their good QOL.     

激素抵抗性前列腺癌化疗15例报告

目的：探讨多西紫杉醇联合泼尼松治疗内分泌治疗失败前列腺癌的应用价值。方法：入选15例非激素依赖性前列腺癌患者,给予多西紫杉醇75 mg/m^2,第1天;泼尼松5 mg bid,第1-21天,21天为1个周期,每例接受化疗6-10个周期不等。结果：本组病例随访6-87周,中位61周。其中26.7%（4/15）完全缓解,46.7%（7/15）部分缓解,20.0%（3/15）稳定,6.66%（1/15）进展。缓解和稳定患者的PSA进展中位时间是40.3周（13-67周）。8例骨痛患者中5例疼痛缓解。 中位生存期大于12个月。不良反应可耐受。结论：多西紫杉醇联合泼尼松治疗激素抵抗性前列腺癌有较好疗效,不良反应轻。     

Clinical outcome of oral uracil/tegafur (UFT) therapy for patients with hormone refractory prostate cancer

There is no standard therapeutic strategy for advanced hormone refractory prostate cancer after the initial hormonal therapy fails. The objective of this study was to retrospectively evaluate the clinical outcome of the oral anticancer agent, uracil/tegafur (UFT) for patients with hormone refractory prostate cancer. This study included 68 patients with hormone refractory prostate cancer treated by oral administration of UFT (300-600 mg/day). All patients had previously received maximum androgen blockade (MAB) which failed. In this series, response was defined as more than 50% decrease from the baseline prostate specific antigen (PSA) value at the start of second line therapy. Upon initiating administration of UFT, a reduction in PSA value was observed in 41 of the 68 patients (60.3%), among whom 13 (19.1%) were regarded as responders; however, PSA value continued to increase in the remaining 27 (39.7%). Median duration of PSA response was 7 months (range 1-22 months). During the observation period, there were no severe side effects due to UFT administration, but 7 patients transiently presented appetite loss. Patients without bone metastasis at the initial diagnosis or whose serum PSA value at the start of UFT therapy was less than 2.0 ng/ml showed a significantly higher incidence of PSA response to UFT; however, other factors examined had no significant impact on PSA response to UFT. Furthermore, cause-specific survival in responders to UFT therapy was significantly better than that in non-responders. These findings suggest that administration of UFT after the failure of initial MAB therapy can achieve a comparatively favorable PSA response without severe side effects; therefore, it may be worthy to consider administering UFT to patients with hormone refractory prostate cancer.     

Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer: re-induction of endocrine sensitivity an unexpected finding

The management of androgen independent prostate cancer is increasingly disputed. Diethylstilbestrol and steroids have useful second-line activity in its management. The value of chemotherapy still remains contentious. This paper reports a phase 2 study of two orally active chemotherapy drugs in patients who are absolutely hormone refractory having failed primary androgen blockade and combined oestrogens and corticosteroids. In total, 37 patients who were biochemically castrate with absolute hormone refractory prostate cancer and performance status of 0-3 were enrolled. Therapy consisted of chlorambucil 1 mg kg(-1) given as 6 mg a day until the total dose was reached and lomustine 2 mg kg(-1) given every 56 days (CL56). During this time all hormone therapy was stopped. One patient normalised his PSA with a further two having a greater than 50% decline leading to an objective response rate of 10%. The median time to progression was 3.6 months with an overall survival of 7.1 months. The median survival of this group of patients from first becoming androgen independent was 23.5 months. Eight of 17 (47%) patients who were subsequently re-challenged with hormonal therapy following failure of chemotherapy had a further PSA reduction, three (17%) of which were >50%. The median progression-free interval for the eight patients was 4 months. In conclusion, CL56 has a low objective response rate in the management of absolute hormone refractory prostate cancer. Toxicity was mild. Re-induction of hormone sensitivity following failure of chemotherapy was an unexpected finding that requires further study.     

培美曲塞联合顺铂方案治疗转移性乳腺癌的临床观察

目的观察培美曲塞联合顺铂方案治疗复发转移性乳腺癌的临床疗效及不良反应。方法 32例转移性乳腺癌患者,采用培美曲塞联合顺铂化疗方案：培美曲塞500mg/m2,顺铂75mg/m2,静脉滴注,每3周重复。每2个化疗周期评价疗有效率（RR）、疾病控制率（DCR）和不良反应,计算疾病进展时间（TTP）和总生存期（OS）。结果 32例入组患者均可评价临床疗效及不良反应,其中CR1例,PR11例,SD6例,PD14例。随访时间为12.5个月,中位TTP为4.2个月,中位OS为8.5个月。最常见的不良反应是消化道反应和中性粒细胞减低。结论即使转移性乳腺癌患者已对多种化疗药物产生耐药,培美曲塞联合顺铂方案仍是治疗转移性乳腺癌的有效方案,且其血液学和非血液学毒性耐受性较好。     

激素抵抗性前列腺癌化疗15例报告

目的:探讨多西紫杉醇联合泼尼松治疗内分泌治疗失败前列腺癌的应用价值.方法:入选15例非激素依赖性前列腺癌患者,给予多西紫杉醇75 mg /m2,第1天;泼尼松5 mg bid,第1 -21 天,21天为1 个周期,每例接受化疗6-10个周期不等.结果:本组病例随访6 -87 周,中位61周.其中26.7% (4 /15)完全缓解,46.7% (7 /15 ) 部分缓解,20.0% ( 3 /15 ) 稳定,6.66% (1 /15)进展.缓解和稳定患者的PSA进展中位时间是40.3周(13-67周).8例骨痛患者中5例疼痛缓解.中位生存期大于12个月.不良反应可耐受.结论:多西紫杉醇联合泼尼松治疗激素抵抗性前列腺癌有较好疗效,不良反应轻.     

Complete disappearance of metastatic lung tumors and mediastinal lymphnode in a case of hepatocellular carcinoma treated by low-dose 5-fluorouracil/cisplatin therapy

We report a case of complete disappearance of multiple lung metastases and mediastinal lymphnode metastasis by intravenous administration of 5-fluorouracil/cisplatin (FP) after operation for primary hepatocellular carcinoma (HCC). A 54-year-old male was diagnosed with HCC associated with alcoholic liver cirrhosis. He also had a single lung metastasis at the time of diagnosis. After hepatic resection for HCC, the metastatic tumor progressed and became multiple lesions with mediastinal lymphnode involvements. Low-dose FP therapy was performed. Then, 250 mg/m(2)/day of 5-fluorouracil was given intravenously for 5 days weekly by continuous infusion and 10 mg/m(2)/day of cisplatin by intravenous infusion. Both lung metastases and mediastinal lymphnode metastasis were decreasing after six cycles of this therapy. Because of alcoholism and liver damage, chemotherapy could not be continued. But all metastatic lesions were completely disappeared ten months after this therapy. Bone marrow suppression (grade 4) was observed during the chemotherapy but resolved by interruption of treatment. Low-dose FP therapy may well be useful for patients suffering from advanced HCC with distant metastasis.     

Phase I trial of the combination of daily estramustine phosphate and intermittent docetaxel in patients with metastatic hormone refractory prostate carcinoma

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 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 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.     

Characterization of prognostic factors and efficacy in a phase-II study with docetaxel and estramustine for advanced hormone refractory prostate cancer

BACKGROUND: Docetaxel based chemotherapy not only reduces pain and improves quality of life in advanced hormone refractory prostate cancer (HRPC), but it also improves survival. We investigated the combination of docetaxel and estramustine in patients with HRPC regarding efficacy and prognostic parameters. PATIENTS AND METHODS: We conducted a phase-II trial, administering docetaxel (70 mg/m(2) i.v., day 2, every 3 weeks) and estramustine (280 mg 3 times daily p.o., 1 day prior to docetaxel, on 5 consecutive days) to patients with HRPC. Patients were monitored for PSA (prostate-specific antigen) response and toxicity. RESULTS: 62 patients were treated. The median age was 67.5 years, the median PSA was 177.9 ng/ml. The median number of cycles was 6. The median time to progression (TTP) and median survival time were 14 (+/-2) and 24 (+/-5) months, respectively. A = 50% decrease in PSA levels from baseline occurred in 38 (61.3%) patients of whom 25 (40.3%) had a = 75% PSA decrease. The main grade 3-4 hematologic toxicities were neutropenia 34% and anemia 18%. CONCLUSIONS: The combination of docetaxel and estramustine exerts substantial activity in HRPC suggesting an overall survival benefit with manageable toxicity. This trial also demonstrated a survival advantage for patients with early chemotherapeutic intervention. We identified PSA relapse, baseline PSA and hemoglobin as valuable prognostic factors in this setting.