Paclitaxel-cisplatin combination versus sequential paclitaxel and cisplatin in metastatic breast cancer and the clinical importance of plasma micro-RNA : A phase II randomized trial / Wafa Hussien Buhoush ; Supervised Mostafa Mahmoud Elserafi , Ibrahim Mohammed Abdelsalam , Ahmed Abdelmabood Zeeneldin

Thesis (Ph.D.) - Cairo University - National Cancer Institute - Department of Oncology (Medical)

Introduction: Breast cancer (BC) is the commonest cancer among females in Egypt and Libya. Patients present at advanced stages and more than 50% of them will develop metastasis (MBC) at some point. Compared to single agents, combination chemotherapy produces higher response rates (RR), longer progression-free survival (PFS) than single agents. This is associated with remarkably higher toxicities. At the same time, overall survival (OS) is comparable. We aimed to compare safety and efficacy of combination and sequential chemotherapy. Methods: in this a randomized phase II study, 46 patients were randomized to receive 6 cycles of the combination of paclitaxel (175 mg/sq m) and cisplatin (70 mg/sq m) (combination PC) or paclitaxel for 3 cycles followed by cisplatin for 3 cycles (sequential PC). Endpoints were RR, PFS, OS and safety. Plasma miR10-b level was assessed in 19 health controls and in 28 MBC patients both at baseline and at the end of therapy. Results: Both combination and sequential PC produced similar RR (52% in both arms) and disease control rates (78% vs. 74%). Responses were faster in the combination arm. PFS was longer in the combination compared to the sequential arm (8.2 vs. 5 months; p=0.06). Overall survival was comparable in both arms (16.5% vs. 18.8 months; p=0.87). Combination was more toxic than sequential PC. Grade 3 toxicities were higher combination PC compared to sequential PC (40% vs. 4%, %; p= 0.007). miR10-b was significantly higher in MBC compared to healthy controls. It was higher with aggressive disease (i.e. hormone-receptor negative and HER-2 positive disease) and higher levels were associated with shorter PFS and OS. Moreover, miR10-b levels decrease at the end of therapy compared with base-line values. Conclusion: sequential agent chemotherapy proved almost similar efficacy to combination chemotherapy but with much lower toxicities. This should be considered the standard practice in most instances. miR10-b has potential diagnostic, prognostic and predictive roles in breast cancer

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