Meistrich M L, Wilson G, Brown B W, da Cunha M F, Lipshultz L I
Department of Experimental Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cancer. 1992 Dec 1;70(11):2703-12. doi: 10.1002/1097-0142(19921201)70:11<2703::aid-cncr2820701123>3.0.co;2-x.
Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men.
To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy.
From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2.
Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2.
采用多药化疗方案或放射疗法治疗癌症可导致年轻男性出现不同持续时间的暂时性无精子症或永久性无精子症。
为确定何种药物及何种剂量会导致长期或永久性无精子症，对尤因肉瘤和软组织肉瘤患者在使用CYADIC（环磷酰胺、阿霉素和达卡巴嗪）或CYVADIC（在CYADIC基础上加用长春新碱）治疗前、治疗期间及治疗后进行精液分析。部分患者还接受了其他药物治疗或放射治疗。
精子生成量从与对照对象相似的预处理水平在治疗后4个月内降至无精子症。部分患者治疗后精子生成量恢复；40%的男性在治疗后5年恢复到正常精子生成水平。此后很少有患者精子生成量持续恢复。环磷酰胺的累积剂量是恢复到正常精子生成水平的最主要决定因素；接受剂量低于7.5 g/m2（中位数为4.1 g/m2）的患者中约70%恢复，但剂量超过7.5 g/m2时只有10%恢复。
因此，年轻男性使用CYADIC和CYVADIC方案存在永久性不育风险，尤其是当环磷酰胺累积剂量大于7.5 mg/m2时。
