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TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: a non-randomized retrospective study.

Kupryjanczyk J, Kraszewska E, Ziolkowska-Seta I, Madry R, Timorek A, Markowska J, Stelmachow J, Bidzinski M, Polish Ovarian Cancer Study Group (POCS - BMC Cancer (2008)

Bottom Line: We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland. jkupry@coi.waw.pl

ABSTRACT

Background: 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.

Methods: 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(-)].

Results: 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.

Conclusion: 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.

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Kaplan-Meier curves for overall survival in the TP53(-) group in patients at the age of 53 years (median) or younger.
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Figure 2: Kaplan-Meier curves for overall survival in the TP53(-) group in patients at the age of 53 years (median) or younger.

Mentions: Overall survival curves have shown that in the TP53(-) group patient's age over median determined benefits from TP therapy (log rank: p = 0.0027, fig. 1). TP therapy in the group of patients ≤53 yrs did not seem to improve overall survival when compared with PC/PAC therapy (log rank: p = 0.37, fig. 2). In multivariate analysis there was a trend only (beyond the border of significance) suggesting that TP therapy might diminish the risk of death in patients older than 53 years (Table 2).


TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: a non-randomized retrospective study.

Kupryjanczyk J, Kraszewska E, Ziolkowska-Seta I, Madry R, Timorek A, Markowska J, Stelmachow J, Bidzinski M, Polish Ovarian Cancer Study Group (POCS - BMC Cancer (2008)

Kaplan-Meier curves for overall survival in the TP53(-) group in patients at the age of 53 years (median) or younger.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2268700&req=5

Figure 2: Kaplan-Meier curves for overall survival in the TP53(-) group in patients at the age of 53 years (median) or younger.
Mentions: Overall survival curves have shown that in the TP53(-) group patient's age over median determined benefits from TP therapy (log rank: p = 0.0027, fig. 1). TP therapy in the group of patients ≤53 yrs did not seem to improve overall survival when compared with PC/PAC therapy (log rank: p = 0.37, fig. 2). In multivariate analysis there was a trend only (beyond the border of significance) suggesting that TP therapy might diminish the risk of death in patients older than 53 years (Table 2).

Bottom Line: We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland. jkupry@coi.waw.pl

ABSTRACT

Background: 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.

Methods: 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(-)].

Results: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus