Bokemeyer C
Abteilung Hämatologie/Onkologie, Medizinische Hochschule Hannover
Med Klin (Munich). 1996 Apr 12;91 Suppl 3:60-7.
The present analysis deals with 2 main problems among therapy-associated late toxicities in patients after curative treatment for malignant tumors, such as Hodgkin's disease and testicular cancer: gonadal late toxicities in young patients after treatment for lymphomas and the risk of secondary neoplasia after curative treatment for malignant male germ cell tumors.
PATIENTS/RESULTS: In 66 patients with Hodgkin's disease and 24 patients with non-Hodgkin's lymphomas ( < 45 years), who were in complete remission for more than 2 years after chemo- and/or radiotherapy, gonadal damages were analysed based on hormone levels (FSH, LH, testosterone, estrogen), clinical examination and patients' histories. 50% of female patients with Hodgkin's disease suffered from premature ovarian failure and 65% of men were either sub- or infertile. In contrast, only 18% of patients treated for non-Hodgkin's lymphoma showed signs of gonadal toxicity. The risk for gonadal toxicity in patients with Hodgkin's disease was related to the use of procarbacine as a part of the COPP-regimen and to infradiaphragmatic radiotherapy. Sperm conservation should be offered to male patients prior to therapy. In female patients with Hodgkin's disease hormone levels should be evaluated after therapy and substitution should be initiated early in order to avoid osteoporosis, an increased cardiovascular risk and psychological problems. In patients with testicular cancer it could be demonstrated that current therapeutic strategies are associated with a small but identifiable risk for secondary neoplasia: radiotherapy causes a 2- to 3-fold increased risk for solid cancers and chemotherapy, particularly the use of etoposide-based regimens, is associated with secondary leukemias. However, a risk-benefit analysis shows that cure rates above 80% for patients with metastatic disease will outweigh the risk of secondary neoplasia.
The investigation of therapy-associated late toxicities will remain an important issue even with the use of new treatment approaches such as high-dose therapy. Prospective evaluation of late toxicities needs to be incorporated into new studies for the curative treatment of malignant tumors.
本分析涉及恶性肿瘤（如霍奇金淋巴瘤和睾丸癌）根治性治疗后患者与治疗相关的晚期毒性中的两个主要问题：淋巴瘤治疗后年轻患者的性腺晚期毒性以及男性生殖细胞恶性肿瘤根治性治疗后的继发肿瘤风险。
患者/结果：对66例霍奇金淋巴瘤患者和24例非霍奇金淋巴瘤患者（年龄<45岁）进行了分析，这些患者在化疗和/或放疗后完全缓解超过2年，基于激素水平（促卵泡生成素、促黄体生成素、睾酮、雌激素）、临床检查和患者病史对性腺损伤进行了分析。50%的霍奇金淋巴瘤女性患者患有卵巢早衰，65%的男性患者存在生育功能减退或不育。相比之下，接受非霍奇金淋巴瘤治疗的患者中只有18%表现出性腺毒性迹象。霍奇金淋巴瘤患者性腺毒性的风险与作为COPP方案一部分使用丙卡巴肼以及膈下放疗有关。应在治疗前为男性患者提供精子保存。对于霍奇金淋巴瘤女性患者，治疗后应评估激素水平，并应尽早开始替代治疗，以避免骨质疏松症、心血管风险增加和心理问题。对于睾丸癌患者，可以证明当前的治疗策略与继发肿瘤存在虽小但可识别的风险相关：放疗会使实体癌风险增加2至3倍，化疗，特别是使用依托泊苷为基础的方案，与继发性白血病有关。然而，风险效益分析表明，转移性疾病患者80%以上的治愈率将超过继发肿瘤的风险。
即使采用高剂量治疗等新的治疗方法，对与治疗相关的晚期毒性的研究仍将是一个重要问题。晚期毒性的前瞻性评估需要纳入恶性肿瘤根治性治疗的新研究中。
