Neoadjuvant therapy of BRCA1-driven ovarian cancer by combination of cisplatin, mitomycin C and doxorubicin.

BACKGROUND: Cisplatin, mitomycin C and anthracyclines demonstrate high activity in BRCA1-deficient tumors. This study aimed to evaluate the efficacy of the triplet combination of these drugs in BRCA1-driven high-grade serous ovarian carcinomas (HGSOCs). METHODS: Ten HGSOC patients with germ-line BRCA1 mutation received neoadjuvant chemotherapy (NACT) consisting of mitomycin C 10 mg/m2 (day 1), doxorubicin 30 mg/m2 (days 1 and 8) and cisplatin 80 mg/m2 (day 1), given every 4 weeks (MAP regimen). The comparator group included 16 women, who received standard NACT combination of paclitaxel 175 mg/m2 and carboplatin (6 AUC), given every 3 weeks (TCbP scheme). RESULTS: None of the patients treated by the MAP scheme demonstrated complete pathologic response in ovaries, while 4 women showed absence of tumor cells in surgically excised omental specimens. When chemotherapy response scores (CRS) were considered, poor responsiveness (CRS 1) was not observed in the MAP group, but was common for the TCbP regimen (6/16 (38 %) for ovaries and 5/16 (31 %) for omentum; p = 0.05 and 0.12, respectively). Median treatment-free interval (TFI) was not reached in women treated by the MAP, but was 9.5 months for the TCbP scheme (p = 0.1). The rate of the recurrence within 1 year after the completion of the treatment was 4/10 (40 %) for the MAP and 10/13 (77 %) for the TCbP (p = 0.1). CONCLUSIONS: The attempt to intensify NACT by administering combination of 3 drugs did not result in high rate of complete pathologic responses. However, there was a trend towards higher efficacy of the MAP regimen versus conventional TCbP scheme with regard to CRS and clinical outcomes.

Efficacy of Neoadjuvant Therapy With Cisplatin Plus Mitomycin C in BRCA1-Mutated Ovarian Cancer.

OBJECTIVES: Cisplatin and mitomycin C exert high activity towards BRCA1-deficient cells. This study aimed to evaluate the efficacy of a combination of these drugs in hereditary BRCA1-associated ovarian cancer (OC). METHODS: Twelve OC patients, who could not be treated by primary debulking surgery owing to extensive tumor spread, were given neoadjuvant cisplatin (100 mg/m) and mitomycin C (10 mg/m) every 4 weeks for 3 (n = 9), 2 (n = 2), or 4 (n = 1) cycles. RESULTS: The decrease of tumor burden and complete surgical cytoreduction were achieved in all patients. Pathologic complete response, defined as the absence of tumor cells in surgically removed tissues, was observed in 2 (17%) of 12 cases. Retrospective analysis of 62 OC in BRCA1 mutation carriers subjected to conventional neoadjuvant chemotherapy schemes revealed 36 objective tumor responses (58%) and 37 instances (60%) of complete cytoreductive surgery; however, none of these patients demonstrated pathologic complete response. CONCLUSIONS: The combination of cisplatin plus mitomycin C showed promising results in BRCA1-driven OC and therefore deserves further clinical evaluation.

Both heat and new chemotherapeutic drug dioxadet in hyperthermic intraperitoneal chemoperfusion improved survival in rat ovarian cancer model.

BACKGROUND AND OBJECTIVES: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the time of Cytoreductive Surgery (CRS) is an actively researched treatment in patients with advanced ovarian cancer. Relative contribution of heat and chemotherapeutic agents during HIPEC as well as efficacy of a new agent dioxadet for regional chemotherapy in a rat model of ovarian cancer was studied. METHODS: Sixty rats were divided into three groups: no treatment control group (n = 19), hyperthermia without chemotherapy (HIPEP) (n = 14), HIPEC + cisplatin (n = 14), HIPEC + dioxadet (n = 13). The intra-abdominal tumor was not resected. End points were: median survival (primary), cause of death (secondary). RESULTS: The median survival of the animals in the control group, HIPEP group, HIPEC + cisplatin, HIPEC + dioxadet were 9 (CI; 8-23), 22.5 (CI; 12-43), 25.5 (CI; 13-62), 49 (Cl; 28-70) days, respectively. The P-values control versus HIPEP, HIPEC + cisplatin versus HIPEC + dioxadet were 0.006, 0.002, and 0.001, respectively. CONCLUSION: During HIPEC both the heat and the cytotoxic drug had antitumor effects in a rat ovarian cancer model. Dioxadet showed potential as a drug for regional chemotherapy. J. Surg. Oncol. 2016;113:438-442. © 2015 Wiley Periodicals, Inc.