目的 评价188Re-1-羟基-1,1-二膦酸钠乙烷(即依替膦酸盐,HEDP)治疗肿瘤骨转移疼痛患者的安全性.方法 符合入选标准的31例患者(前列腺癌10例,乳腺癌9例,肺癌3例,肝癌5例,直肠癌2例,食管癌1例,肾癌1例,均随时间顺序人选)知情同意后接受了按体质量肘静脉单次注射188ReHEDP,据药物递增剂量分为4个组:20 MBq/kg组6例、30 MBq/kg组6例、40 MBq/kg组9例、50 MBq/kg组10例.低剂量组安全性分析结束并显示安全后,才开始下一剂量组试验.如果患者出现由于用药引起的不可耐受的、WHO公布的Ⅲ或Ⅳ级骨髓毒性,即终止剂量递增,并认为前一组剂量为最大可接受剂量.观察指标包括给药前及给药后8周内每例患者的生命体征(用药后1,6,12,24,48,72 h和1,2,3,4,6,8周),血细胞计数(用药后1,2,3,4,6和8周),心电图,肝、肾功能,ALP(用药后4,8周),"反跳痛"以及不良反应等.统计分析主要针对符合方案集(PP)人群,包括统计描述和统计推断(t检验).结果 31例患者中有27例属于PP人群:20 MBq/kg组5例、30 MBq/kg组5例、40 MBq/kg组8例、50 MBq/kg组9例.在受试剂量范围内,没有观察到188Re-HEDP对患者生命体征、心电图、肝肾功能和ALP的不良影响.20 MBq/kg组的5例患者中仅1例自细胞出现WHO Ⅰ级毒性;30 MBq/kg组5例患者中2例白细胞出现WHO Ⅰ级毒性,其中1例合并血小板Ⅲ级毒性,但给药后8周白细胞和血小板均恢复正常;40 MBq/kg组8例患者中2例白细胞和血小板同时出现毒性反应,分别为WHO Ⅰ级和Ⅱ级,表现为白细胞和血小板同时、同级减低;50 MBq/kg组9例患者中3例白细胞出现WHOⅡ级毒性.全部患者的血小板均在给药后4周达最低水平,平均为143.5×109/L;白细胞均在给药后6周达最低水平,平均为5.4×109/L(两者与给药前基线值比较,t值分别为3.1325和3.3156,P均＜0.05),给药后8周自细胞和血小板均恢复到基线水平;而血红蛋白在给药后8周最低(与基线值比较,t值为3.4917,P＜0.05).PP人群27例中有2例出现"反跳痛",发生率7.41%(2/27).结论 按体质量注射188Re-HEDP 20,30,40和50 MBq/kg对肿瘤骨转移患者均无明显毒性及不良反应,且随着用药剂量增加,188Re-HEDP对骨髓的抑制有增加趋势.
目的 評價188Re-1-羥基-1,1-二膦痠鈉乙烷(即依替膦痠鹽,HEDP)治療腫瘤骨轉移疼痛患者的安全性.方法 符閤入選標準的31例患者(前列腺癌10例,乳腺癌9例,肺癌3例,肝癌5例,直腸癌2例,食管癌1例,腎癌1例,均隨時間順序人選)知情同意後接受瞭按體質量肘靜脈單次註射188ReHEDP,據藥物遞增劑量分為4箇組:20 MBq/kg組6例、30 MBq/kg組6例、40 MBq/kg組9例、50 MBq/kg組10例.低劑量組安全性分析結束併顯示安全後,纔開始下一劑量組試驗.如果患者齣現由于用藥引起的不可耐受的、WHO公佈的Ⅲ或Ⅳ級骨髓毒性,即終止劑量遞增,併認為前一組劑量為最大可接受劑量.觀察指標包括給藥前及給藥後8週內每例患者的生命體徵(用藥後1,6,12,24,48,72 h和1,2,3,4,6,8週),血細胞計數(用藥後1,2,3,4,6和8週),心電圖,肝、腎功能,ALP(用藥後4,8週),"反跳痛"以及不良反應等.統計分析主要針對符閤方案集(PP)人群,包括統計描述和統計推斷(t檢驗).結果 31例患者中有27例屬于PP人群:20 MBq/kg組5例、30 MBq/kg組5例、40 MBq/kg組8例、50 MBq/kg組9例.在受試劑量範圍內,沒有觀察到188Re-HEDP對患者生命體徵、心電圖、肝腎功能和ALP的不良影響.20 MBq/kg組的5例患者中僅1例自細胞齣現WHO Ⅰ級毒性;30 MBq/kg組5例患者中2例白細胞齣現WHO Ⅰ級毒性,其中1例閤併血小闆Ⅲ級毒性,但給藥後8週白細胞和血小闆均恢複正常;40 MBq/kg組8例患者中2例白細胞和血小闆同時齣現毒性反應,分彆為WHO Ⅰ級和Ⅱ級,錶現為白細胞和血小闆同時、同級減低;50 MBq/kg組9例患者中3例白細胞齣現WHOⅡ級毒性.全部患者的血小闆均在給藥後4週達最低水平,平均為143.5×109/L;白細胞均在給藥後6週達最低水平,平均為5.4×109/L(兩者與給藥前基線值比較,t值分彆為3.1325和3.3156,P均＜0.05),給藥後8週自細胞和血小闆均恢複到基線水平;而血紅蛋白在給藥後8週最低(與基線值比較,t值為3.4917,P＜0.05).PP人群27例中有2例齣現"反跳痛",髮生率7.41%(2/27).結論 按體質量註射188Re-HEDP 20,30,40和50 MBq/kg對腫瘤骨轉移患者均無明顯毒性及不良反應,且隨著用藥劑量增加,188Re-HEDP對骨髓的抑製有增加趨勢.
목적 평개188Re-1-간기-1,1-이련산납을완(즉의체련산염,HEDP)치료종류골전이동통환자적안전성.방법 부합입선표준적31례환자(전렬선암10례,유선암9례,폐암3례,간암5례,직장암2례,식관암1례,신암1례,균수시간순서인선)지정동의후접수료안체질량주정맥단차주사188ReHEDP,거약물체증제량분위4개조:20 MBq/kg조6례、30 MBq/kg조6례、40 MBq/kg조9례、50 MBq/kg조10례.저제량조안전성분석결속병현시안전후,재개시하일제량조시험.여과환자출현유우용약인기적불가내수적、WHO공포적Ⅲ혹Ⅳ급골수독성,즉종지제량체증,병인위전일조제량위최대가접수제량.관찰지표포괄급약전급급약후8주내매례환자적생명체정(용약후1,6,12,24,48,72 h화1,2,3,4,6,8주),혈세포계수(용약후1,2,3,4,6화8주),심전도,간、신공능,ALP(용약후4,8주),"반도통"이급불량반응등.통계분석주요침대부합방안집(PP)인군,포괄통계묘술화통계추단(t검험).결과 31례환자중유27례속우PP인군:20 MBq/kg조5례、30 MBq/kg조5례、40 MBq/kg조8례、50 MBq/kg조9례.재수시제량범위내,몰유관찰도188Re-HEDP대환자생명체정、심전도、간신공능화ALP적불량영향.20 MBq/kg조적5례환자중부1례자세포출현WHO Ⅰ급독성;30 MBq/kg조5례환자중2례백세포출현WHO Ⅰ급독성,기중1례합병혈소판Ⅲ급독성,단급약후8주백세포화혈소판균회복정상;40 MBq/kg조8례환자중2례백세포화혈소판동시출현독성반응,분별위WHO Ⅰ급화Ⅱ급,표현위백세포화혈소판동시、동급감저;50 MBq/kg조9례환자중3례백세포출현WHOⅡ급독성.전부환자적혈소판균재급약후4주체최저수평,평균위143.5×109/L;백세포균재급약후6주체최저수평,평균위5.4×109/L(량자여급약전기선치비교,t치분별위3.1325화3.3156,P균＜0.05),급약후8주자세포화혈소판균회복도기선수평;이혈홍단백재급약후8주최저(여기선치비교,t치위3.4917,P＜0.05).PP인군27례중유2례출현"반도통",발생솔7.41%(2/27).결론 안체질량주사188Re-HEDP 20,30,40화50 MBq/kg대종류골전이환자균무명현독성급불량반응,차수착용약제량증가,188Re-HEDP대골수적억제유증가추세.
Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3.3156, 3.4917, all P ＜ 0. 05 compared with baseline). At week 8, the mean level of platelet and leucocyte recovered to baseline. "Bounce pain" was found in 2 of 27 patients (7.41%).Conclusions The dose of 20 MBq/kg, 30 MBq/kg, 40 MBq/kg or 50 MBq/kg of 188Re-HEDP do not cause significant side effects on cancer patients with bone metastases, though there is a tendency that the haematological toxicity may increase as the dose of 188Re-HEDP increases.
