Bokemeyer C, Berger C C, Kuczyk M A, Schmoll H J
Department of Hematology/Oncology, Hannover University Medical School, Germany.
J Clin Oncol. 1996 Nov;14(11):2923-32. doi: 10.1200/JCO.1996.14.11.2923.
The current study evaluates the extent and reversibility of late sequelae after chemotherapy in longterm survivors of testicular cancer. The influence of therapy and patient characteristics and the relationship between different toxicities are assessed.
Ninety patients with a median age of 28 years (range, 19 to 53) and a median followup time of 58 months (range, 15 to 159) participated in the clinical examinations, a personal interview, and technical investigations. Overall health and the impact of late toxicity were assessed by the patients. All patients were in complete remission (CR) for at least 1 year. Chemotherapy had consisted of cisplatin (P), bleomycin (B), and vinblastine (V) in 30 patients (33%); P, B, and etoposide (E) in 26 patients (29%); P, B, E, and a vinca alkaloid in 22 patients (24%); and other P-based combination regimens in 12 patients (13%).
Alterations of gonadotropin levels (follicle-stimulating hormone [FSH] luteinizing hormone [LH]) in up to 68% of patients and Leydig cell insufficiency in one third of patients were the most frequently detected abnormalities. Approximately 20% of patients had low serum magnesium [Mg] or phosphate levels, or elevated creatinine levels. Cardiovascular risk factors were identified in one third of patients with elevated serum cholesterol levels with or without obesity; 15% had developed arterial hypertension after chemotherapy. The most frequent symptomatic toxicities were Raynaud's phenomenon (RP) in 30% of patients, ototoxicity in 21%, and peripheral neuropathy in 17%. Major risk factors for the development of toxicity were cumulative dose of P (P < .0001 for ototoxicity and neurotoxicity; P < .01 for overall toxicity, gonadal toxicity, and dehydroepiandrosteron elevation; P < .05 for hypertension and Mg depletion) and type of chemotherapy (57% of PVB-treated patients v25% of PEB +/- vincristine-treated patients with RP; P < .01).
The cumulative dose of P was a major predictor for toxicity. Patients and treatment characteristics such as noise exposure, age, history of smoking, and mode of B application were less important. Further clinical trials should evaluate the sequelae of chemotherapy treatment for testicular cancer prospectively.
本研究评估睾丸癌长期幸存者化疗后晚期后遗症的程度及可逆性。评估治疗方法、患者特征的影响以及不同毒性之间的关系。
90例患者参与了临床检查、个人访谈及技术调查，患者中位年龄为28岁（范围19至53岁），中位随访时间为58个月（范围15至159个月）。患者评估了总体健康状况及晚期毒性的影响。所有患者均处于完全缓解（CR）状态至少1年。30例患者（33%）的化疗方案为顺铂（P）、博来霉素（B）和长春碱（V）；26例患者（29%）为P、B和依托泊苷（E）；22例患者（24%）为P、B、E和一种长春花生物碱；12例患者（13%）为其他基于P的联合方案。
高达68%的患者促性腺激素水平（促卵泡激素[FSH]、黄体生成素[LH]）改变，三分之一的患者存在睾丸间质细胞功能不全，这些是最常检测到的异常情况。约20%的患者血清镁[Mg]或磷酸盐水平低，或肌酐水平升高。三分之一血清胆固醇水平升高的患者（无论是否肥胖）存在心血管危险因素；15%的患者化疗后出现动脉高血压。最常见的有症状毒性反应为30%的患者出现雷诺现象（RP），21%的患者出现耳毒性，17%的患者出现周围神经病变。毒性发生的主要危险因素为P的累积剂量（耳毒性和神经毒性P <.0001；总体毒性、性腺毒性和脱氢表雄酮升高P <.01；高血压和镁缺乏P <.05）以及化疗类型（接受PVB治疗的患者中有57%发生RP，而接受PEB±长春新碱治疗的患者中有25%发生RP；P <.01）。
P的累积剂量是毒性的主要预测因素。患者及治疗相关特征如噪声暴露、年龄、吸烟史和B的应用方式等则不太重要。进一步的临床试验应前瞻性地评估睾丸癌化疗治疗的后遗症。
