p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma

Purpose: The p53 gene plays a critical role in cellular response to DNA dam age and has been implicated in the response to platinum compounds in ovaria n carcinoma patients. Because taxanes could induce p53-independent apoptosi s, we assessed the relevance of p53 gene status to response in ovarian carc inoma patients receiving paclitaxel and platinum-containing chemotherapy. Patients and Methods: Forty-eight previously untreated patients with advanc ed disease received standard paclitaxel/platinum-based chemotherapy. In tum or specimens collected at the time of initial surgery, before therapy, p53 gene status and expression were examined by single-strand conformation poly morphism, sequence analysis, and immunohistochemical analysis. Microsatelli te instability analysis was performed on available sampler from 30 patients . Results: Thirty-four (71%) of the 48 patients had ct clinical response. Pat hologic complete remission was documented in 13 (27%) of 48 patients. p53 m utations were detected in 29 (60%) of 48 tumors. Among the patients with mu tant p53 tumors, 25 patients (86%) responded to chemotherapy. Only nine (47 %) of 19 patients with wild-type p53 tumors responded to the same treatment . The overall response rate and the complete remission rate were significan tly higher among patients with mutant p53 tumors than among patients with w ild-type p53 tumors (P = .008). Most of the tested tumors not associated wi th complete remission (10 of 12 tumors) were also characterized by microsat ellite instability. The complete remission rate was higher among patients w ith tumors without microsatellite instability (five of seven patients). Conclusion: In contrast to the limited efficacy of treatment with paclitaxe l in combination with standard platinum doses against wild-type p53 ovarian tumors, patients with mutant p53 ovarian tumors were more responsive to pa clitaxel-based chemotherapy. The pattern of response to chemotherapy contai ning paclitaxel is different from that associated with high-dose cisplatin therapy. Determining p53 mutational status can be useful in predicting ther apeutic response to drugs effective in ovarian carcinoma. (C) 2000 by Ameri can Society of Clinical Oncology.