Breton Xavier, Lechevallier Eric, Coulange Christian
Service d'Urologie, Hôpital Salvator, Marseille, France.
Prog Urol. 2005 Jun;15(3):398-404.
The current management of hormone-refractory metastatic prostate cancer is purely palliative. The use of chemotherapy in this indication was revised in 1996, based on the results of studies with a combination of mitoxantrone and prednisone. This combination demonstrated a significant improvement of quality of life (+48%) and pain (+30%), but without any overall survival benefit. Two studies using taxols, TAX_327 and SWOG_9916, were published in the New England Journal of Medicine on 7 October 2004, with, for the first time, a median overall survival benefit of 2 months. However, the encouraging results of these 2 studies, which will probably modify the management of hormone-refractory prostate cancer, need to be interpreted cautiously. First of all, they were conducted in selected study populations (mean age less than 70 years, Kamofsky index greater than 80% in more than 85% of cases, local disease control in more than 70% of cases). They also comprise many methodological imprecisions and biases with especially, in the TAX 327 study, a change of treatment arm in 1/3 of patients without exclusion of these patients from the final analysis. The results obtained are also at the limit of statistical significance. The target improvement of overall survival, +25% and +33%, respectively, was not achieved at the end of these studies. Finally, from a palliative point of view, only one of these 2 studies (TAX_327) demonstrated a palliative benefit compared to mitoxantrone: 9% for pain, for a sixfold higher cost. Adverse effects were significantly more frequent than with mitoxantrone. Patient selection and details about the indications are necessary. Taxols should not be used systematically in this indication. Furthermore, although several studies are underway, the benefit of taxols at earlier stages of the disease are unknown. Urologists must be aware of the place of chemotherapy in the treatment of prostate cancer in order to remain at the centre of the treatment decision.
目前,激素难治性转移性前列腺癌的治疗纯粹是姑息性的。基于米托蒽醌与泼尼松联合用药的研究结果,1996年对该适应症化疗的使用进行了修订。这种联合用药显示生活质量显著改善(提高48%),疼痛缓解(提高30%),但对总生存期并无益处。2004年10月7日,《新英格兰医学杂志》发表了两项使用紫杉烷类药物的研究(TAX_327和SWOG_9916),首次显示总生存期的中位数获益为2个月。然而,这两项研究令人鼓舞的结果可能会改变激素难治性前列腺癌的治疗方式,但仍需谨慎解读。首先,这些研究是在特定的研究人群中进行的(平均年龄小于70岁,超过85%的病例卡氏指数大于80%,超过70%的病例局部疾病得到控制)。这些研究还存在许多方法上的不精确性和偏差,特别是在TAX 327研究中,三分之一的患者更换了治疗组,而在最终分析中并未将这些患者排除。所获得的结果也处于统计学意义的临界值。在这些研究结束时,并未实现分别提高25%和33%的总生存期改善目标。最后,从姑息治疗的角度来看,这两项研究中只有一项(TAX_327)显示与米托蒽醌相比有姑息治疗益处:疼痛缓解率为9%,但成本高出六倍。不良反应比使用米托蒽醌时明显更频繁。患者选择和适应症细节很有必要。紫杉烷类药物不应在此适应症中常规使用。此外,尽管有几项研究正在进行,但紫杉烷类药物在疾病早期阶段的益处尚不清楚。泌尿科医生必须了解化疗在前列腺癌治疗中的地位,以便在治疗决策中处于核心位置。