A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors.

PURPOSE: This study aimed at evaluating the effect of rucaparib on the pharmacokinetics of rosuvastatin and oral contraceptives in patients with advanced solid tumors and the safety of rucaparib with and without coadministration of rosuvastatin or oral contraceptives. METHODS: Patients received single doses of oral rosuvastatin 20 mg (Arm A) or oral contraceptives ethinylestradiol 30 µg + levonorgestrel 150 µg (Arm B) on days 1 and 19 and continuous doses of rucaparib 600 mg BID from day 5 to 23. Serial blood samples were collected with and without rucaparib for pharmacokinetic analysis. RESULTS: Thirty-six patients (n = 18 each arm) were enrolled and received at least 1 dose of study drug. In the drug-drug interaction analysis (n = 15 each arm), the geometric mean ratio (GMR) of maximum concentration (Cmax) with and without rucaparib was 1.29 for rosuvastatin, 1.09 for ethinylestradiol, and 1.19 for levonorgestrel. GMR of area under the concentration-time curve from time zero to last quantifiable measurement (AUC0-last) was 1.34 for rosuvastatin, 1.43 for ethinylestradiol, and 1.56 for levonorgestrel. There was no increase in frequency of treatment-emergent adverse events (TEAEs) when rucaparib was given with either of the probe drugs. In both arms, most TEAEs were mild in severity and considered unrelated to study treatment. CONCLUSION: Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib. ClinicalTrials.gov NCT03954366; Date of registration May 17, 2019.

Sorafenib as a third line therapy in patients with epithelial ovarian cancer or primary peritoneal cancer: a phase II study.

PURPOSE: New agents are required for the patients with epithelial ovarian cancer (EOC) who progress after first and second line of the treatment. Tumor vasculature targeted agents are potentially active in EOC. We aimed to assess the activity of sorafenib in patients with recurrent EOC who had received two prior therapies. PATIENTS AND METHODS: A phase II non-randomized, open-label, single-arm study aimed to assess the efficacy, safety and tolerance of sorafenib monotherapy as a third line therapy in patients with EOC or primary peritoneal cancer (PPC). Sorafenib was administered as 400 mg twice daily on days 1-28 of each 4-week cycle. The primary end point of the study was to demonstrate the progression free survival (PFS). RESULTS: Eleven patients were enrolled. The median number of cycles was two. Among the 11 patients eligible for efficacy analysis, no patients experienced a partial response or complete response or stable disease lasting longer than 6 months according to RECIST criteria. Thus, the trial stopped at the end of the first stage of study design. The median PFS was 2.00 months (95% CI, 1,80-3,90). The median OS was 11.78 months (95% CI, 7.66 to 15.39). There were no grade 4 toxicities and few grade 3 toxicities. CONCLUSION: Sorafenib fails to achieve sufficient objective response or sustained disease stabilization as third-line treatment for EOC.

Serous peritoneal psammocarcinoma with an aggressive course: a case and review of the literature.

BACKGROUND: Primary serous peritoneal psammocarcinoma (PSPP) is a rare variant of serous carcinoma characterized by massive psammoma body formation and low-grade cytological features. Patients with serous psammocarcinoma have a protracted clinical course and relatively favourable prognosis, although a more aggressive course of PSPP may occur. CASE PRESENTATION: A 52-year-old woman suffering from abdominal pain with ascites and serum CA-125 level substantially elevated underwent an exploratory laparoscopy which revealed bulk disease. The pathology report detected PPSP at the FIGO stage IIIC. The patient received neoadjuvant chemotherapy (3 courses of paclitaxel/pegylated liposomal doxorubicin/carboplatin). Optimal interval debulking surgery was performed as the next step, followed by three courses of adjuvant chemotherapy (paclitaxel/carboplatin). Due to the fact that the patient had residual disease, at the second-look surgery she received consolidation therapy with intraperitoneal and intravenous chemotherapy carboplatin. Eight months after the completion of treatment the patient developed disease recurrence in the peritoneum. Palliative surgery (enterostomy) was performed. Furthermore, the patient received two lines of chemotherapy consisting of cyclophosphamide/cisplatin and then gemcitabine. After twenty five months she developed brain metastases, treated with palliative radiotherapy. The patient died twenty-eight months since her primary presentation of PSPP. CONCLUSION: PSPP is an infrequent variant of epithelial cancer with favourable prognosis. The disease may however, take a more aggressive course. Thus, an aggressive therapy is required to postpone the progression.