Kupryjanczyk Jolanta, Kraszewska Ewa, Ziolkowska-Seta Izabela, Madry Radoslaw, Timorek Agnieszka, Markowska Janina, Stelmachow Jerzy, Bidzinski Mariusz
Department of Molecular Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland.
BMC Cancer. 2008 Jan 29;8:27. doi: 10.1186/1471-2407-8-27.
Taxane-platinum therapy (TP) has replaced platinum-based therapy (PC or PAC, DNA damaging chemotherapy) in the postoperative treatment of ovarian cancer patients; however, it is not always effective. TP53 protein plays a differential role in response to DNA-damaging agents and taxanes. We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC.
We compared the effectiveness of PC/PAC (n = 253) and TP (n = 199) with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+)] and without TP53 accumulation [TP53(-)].
The advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+), and not in the TP53(-) group. In the TP53(+) group taxane-platinum therapy enhanced the probability of complete remission (p = .018), platinum sensitivity (p = .014), platinum highly sensitive response (p = .038) and longer survival (OS, p = .008). Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+) group. In the TP53(-) group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010). However, in the TP53(-) group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077). Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation.
Our results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+) tumors or older than 53 years. In the group of patients < or =53 yrs and with TP53(-) tumors platinum-based therapy is possibly equally efficient. We provide hints for planning randomized trials to verify these observations.
紫杉烷 - 铂类疗法（TP）已在卵巢癌患者术后治疗中取代了铂类疗法（PC或PAC，DNA损伤化疗）；然而，其并非总是有效。TP53蛋白在对DNA损伤剂和紫杉烷的反应中发挥不同作用。我们试图确定从TP中获益最大的患者特征以及那些可用PC治疗的患者特征。
我们比较了PC/PAC（n = 253）和TP（n = 199）在FIGO分期为IIB - IV期的卵巢癌患者中肿瘤TP53积累方面的有效性；这是一项非随机回顾性研究。对452例存档肿瘤进行免疫组化分析；在所有患者以及有TP53积累[TP53(+)]和无TP53积累[TP53(-)]的亚组中，采用Cox模型和逻辑回归模型进行单因素和多因素分析。
在TP53(+)组而非TP53(-)组中观察到紫杉烷 - 铂类疗法优于铂类疗法。在TP53(+)组中，紫杉烷 - 铂类疗法提高了完全缓解概率（p = 0.018）、铂敏感性（p = 0.014）、铂高敏反应（p = 0.038）以及延长了生存期（OS，p = 0.008）。肿瘤分化差削弱了TP53(+)组中紫杉烷 - 铂类疗法的优势。在TP53(-)组中，PC/PAC至少与紫杉烷 - 铂类疗法同样有效，且提高了铂高敏反应的机会（p = 0.010）。然而，在TP53(-)组中，紫杉烷 - 铂类疗法可能降低了53岁以上患者的死亡风险（p = 0.077）。在一些分析中，与紫杉烷 - 铂类疗法呈正相互作用的因素包括子宫内膜样和透明细胞类型、FIGO III期、大块残留肿瘤、患者年龄较大以及肿瘤中等分化。
我们的结果表明，紫杉烷 - 铂类疗法在TP53(+)肿瘤患者或53岁以上患者中尤为合理。在年龄≤53岁且TP53(-)肿瘤的患者组中，铂类疗法可能同样有效。我们为规划随机试验以验证这些观察结果提供了线索。
