EFFICACY AND TOXICITY OF VERY HIGH-DOSE CISPLATIN IN ADVANCED OVARIAN-CARCINOMA - 4-YEAR SURVIVAL ANALYSIS AND NEUROLOGICAL FOLLOW-UP
EFFICACY AND TOXICITY OF VERY HIGH-DOSE CISPLATIN IN ADVANCED OVARIAN-CARCINOMA - 4-YEAR SURVIVAL ANALYSIS AND NEUROLOGICAL FOLLOW-UP
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DOI：
10.1046/j.1525-1438.1993.03010044.x
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发表时间：
1993-01-01
影响因子：
4.8
通讯作者：
MANCUSO, S
中科院分区：
文献类型：
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作者：
PANICI, PB;GREGGI, S;MANCUSO, S
鉴于顺铂的剂量-反应关系陡峭，在既往未经治疗的晚期卵巢癌和术后残留肿瘤（RT）患者中进行了一项关于极高剂量顺铂（HD-CDDP）的初步研究。37名患者（FIGO III-IV期; RT > 0.5 cm）接受了3个疗程的HD-CDDP（疗程为40 mg/m2/day，持续第1-5天，每28天一次）。20例患者（54%）达到临床完全缓解（CR），12例（32%）部分缓解（PR），其余5例（14%）显示疾病稳定或进展（NC-P）。所有20例临床完全缓解者均接受了二次剖腹探查术，除5例病例（病理学CR：40%）外，所有病例均证实CR，RT> 0.52 cm的患者中有71%，RT> 2 cm的患者中有15%（P < 0.001）。4年总生存率为35%（中位数：27个月，范围：7-58+），RT> 0.5-2 cm和> 2 cm的患者分别为53%和20%（P = 0.01）。总体无进展生存率为29.5%（中位数：16个月，范围2-58+），对于RT大于或小于2 cm的患者，其为20%和41.2%（P < 0.05）。病理完全缓解者未接受进一步治疗，3年无病生存率为53%。主要的毒性作用是在所有患者中观察到的迟发性周围神经病变，其中5例（13.5%）伴有需要持续辅助的步态障碍。然而，他们中没有一个成为轮椅依赖者，大约90%的存活患者在18个月的神经系统随访中恢复，这表明顺铂损伤是可逆的。在所有患者中均检测到耳毒性，但只有19%的患者有症状。HD-CDDP在RT> 0.5-2 cm的患者中显示出高活性，表明最小RT的不利意义可以通过强化化学细胞减少来部分克服。严重的神经毒性和重症监护的需要是主要的缺点。进一步的研究应描绘HD-CDDP在最佳减容患者中的确切作用，并且应做出相当大的努力，以快速获得关于神经保护剂在预防剂量限制性神经毒性中的价值的可靠数据。
Given the steep dose-response relationship with cisplatin, a pilot study on very high-dose cisplatin (HD-CDDP) was conducted in previously untreated patients with advanced ovarian carcinoma and postoperative residual tumor (RT). Thirty-seven patients (FIGO stages III-IV; RT > 0.5 cm) received three courses of HD-CDDP (a course of 40 mg m-2 day-1, for days 1-5, every 28 days). Twenty patients (54%) achieved clinical complete response (CR), 12 (32%) partial response (PR), and the remaining five (14%) showed stable or progressive disease (NC-P). All 20 clinically complete responders underwent second-look laparotomy and CR was confirmed in all but five cases (pathologic CR: 40%) and in 71% of patients with > 0.52 cm RT vs. 15 % of those with > 2 cm RT (P < 0.001). The 4-year overall survival was 35% (median: 27 months, range: 7-58+), and 53% vs. 20% for patients with > 0.5-2 cm and > 2 cm RT, respectively (P = 0.01). The overall progression-free survival was 29.5% (median: 16 months, range 2-58+) and for patients with more or less than 2 cm RT it was 20 and 41.2% (P < 0.05). Pathologically complete responders received no further treatment and showed a 3-year disease-free survival of 53%. The major toxic effect was a delayed-onset peripheral neuropathy observed in all patients, five of them (13.5%) with gait disturbances requiring continuous assistance. Nevertheless, none of them became wheelchair dependent and about 90% of the alive patients recovered at the 18-month neurologic follow-up, suggesting that cisplatin damage can be reversible. Ototoxicity was detected in all patients although only 19% of patients were symptomatic. HD-CDDP showed high activity in patients with > 0.5-2 cm RT, suggesting that the adverse significance of minimal RT may be partially overcome through an intensive chemical cytoreduction. Substantial neurotoxicity and the need for intensive care represent the major drawbacks. Further studies should delineate the exact role of HD-CDDP in optimally debulked patients, and a considerable effort should be made in rapidly achieving reliable data on the value of neuroprotectors in the prevention of the dose-limiting neurotoxicity.