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采用博来霉素-依托泊苷-卡铂(BEC(90))联合化疗治疗的睾丸癌患者的睾丸功能

Testicular function in patients with testicular cancer treated with bleomycin-etoposide-carboplatin (BEC(90)) combination chemotherapy.

作者信息

Pectasides Dimitrios, Pectasides Melina, Farmakis Dimitrios, Nikolaou Maria, Koumpou Maria, Kostopoulou Vassiliki, Mylonakis Nikolaos

机构信息

2nd Department of Medical Oncology, Metaxas Memorial Cancer Hospital, 51 Botassi St, 18537 Piraeus, Greece.

出版信息

Eur Urol. 2004 Feb;45(2):187-93. doi: 10.1016/j.eururo.2003.09.010.

Abstract

OBJECTIVE

To investigate the impact of bleomycin-etoposide-carboplatin combination chemotherapy on long-term fertility in patients with testicular germ cell tumors.

METHODS

Twenty-five patients with high risk stage I and IM non-seminomatous germ cell tumors (NSGCT, Group A) and 44 with advanced seminoma or NSGCT (Group B) were treated with bleomycin 30 mg (days 2, 9, 16), etoposide 165 mg/m(2) (days 1-3) and carboplatin 400mg/m(2) or AUC 5 (day 1) (BEC(90)). Treatment was repeated every 3 weeks. Group A patients received 2 cycles of BEC(90), while Group B ones received 4 to 5 cycles of BEC(90). Sperm count and hormonal analyses were examined pre- and post-chemotherapy. Counts were classified as normospermia (NS) if >20 x 10(6)ml(-1), oligospermia (OS) if 1-20 x 10(6)ml(-1) and azoospermia (AS) if <1 x 10(6)ml(-1).

RESULTS

Patients were followed for a median of 2.9 years post-chemotherapy. The post-orchidectomy median luteinizing hormone (LH) serum levels were slightly above the upper normal limit while the serum levels of follicle stimulating hormone (FSH) and testosterone (T) were within the reference interval. Thirty-eight (55%) patients had NS pre-chemotherapy. None of the 14 NS patients who received 2 cycles of BEC(90) had AS post-chemotherapy, while only 1 of the 24 NS patients who were treated with > or =4 cycles of BEC(90) had AS post-treatment. Among the NS patients, 93% and 83%, respectively, remained NS following chemotherapy. Overall, 90% of patients had recovery (61% NS, 29% OS) of spermatogenesis after treatment. The median FSH serum values were significantly elevated at least 1-year post-chemotherapy when compared with the pre-treatment levels. Eighteen months post-chemotherapy the median FSH values had returned to the reference limits. Serum LH and T levels were unaffected by treatment. The pre-treatment sperm count and the bulk of disease were significantly associated with recovery of spermatogenesis. No association was found between recovery of spermatogenesis and 2 or > or =4 cycles of chemotherapy, age > or =30 years and post-chemotherapy lymph node dissection. Thirteen patients (4 with OS) fathered 16 children. No congenital abnormalities occurred in any of these children.

CONCLUSION

The BEC(90) regimen has no major effect on fertility and Leydig cell function. However, carboplatin-based chemotherapy has been proved less effective than cisplatin-based chemotherapy and is not currently used in the treatment of testicular cancer.

摘要

目的

探讨博来霉素-依托泊苷-卡铂联合化疗对睾丸生殖细胞肿瘤患者长期生育能力的影响。

方法

25例高危I期和IM期非精原细胞性生殖细胞肿瘤(NSGCT,A组)患者和44例晚期精原细胞瘤或NSGCT患者(B组)接受博来霉素30mg(第2、9、16天)、依托泊苷165mg/m²(第1 - 3天)和卡铂400mg/m²或AUC 5(第1天)(BEC(90))治疗。每3周重复治疗。A组患者接受2个周期的BEC(90),而B组患者接受4至5个周期的BEC(90)。化疗前后进行精子计数和激素分析。如果精子计数>20×10⁶/ml⁻¹则分类为正常精子症(NS),1 - 20×10⁶/ml⁻¹为少精子症(OS),<1×10⁶/ml⁻¹为无精子症(AS)。

结果

化疗后患者中位随访2.9年。睾丸切除术后黄体生成素(LH)血清中位水平略高于正常上限,而卵泡刺激素(FSH)和睾酮(T)血清水平在参考区间内。38例(55%)患者化疗前为NS。接受2个周期BEC(90)的14例NS患者化疗后均无AS,而接受≥4个周期BEC(90)治疗的24例NS患者中只有1例化疗后出现AS。在NS患者中,分别有93%和83%在化疗后仍为NS。总体而言,90%的患者治疗后精子发生恢复(61%为NS,29%为OS)。与治疗前水平相比,化疗后至少1年FSH血清中位值显著升高。化疗后18个月,FSH中位值恢复到参考范围。血清LH和T水平不受治疗影响。治疗前精子计数和疾病范围与精子发生恢复显著相关。未发现精子发生恢复与2个或≥4个周期化疗、年龄≥30岁及化疗后淋巴结清扫之间存在关联。13例患者(4例为OS)生育了16个孩子。这些孩子均未出现先天性异常。

结论

BEC(90)方案对生育能力和睾丸间质细胞功能无重大影响。然而,已证明基于卡铂的化疗不如基于顺铂的化疗有效,目前未用于睾丸癌治疗。

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