Utilization of intraperitoneal chemotherapy for optimally cytoreduced advanced stage epithelial ovarian cancer: A 10-year single institution experience with a racially diverse urban population.

OBJECTIVES: The goal of our study was to define utilization and clinical results of intraperitoneal (IV/IP) compared to intravenous (IV) chemotherapy in a racially and ethnically diverse population with optimally debulked advanced stage epithelial ovarian cancer. METHODS: After IRB approval, all patients diagnosed with epithelial ovarian cancer that underwent primary cytoreductive surgery at our institution from 2005 to 2016 were identified. Death was verified by the National Social Security Death Index. Patients who received at least one IV/IP cycle were analyzed in the IV/IP cohort. Kaplan-Meier and Cox proportional hazards models were performed. RESULTS: 96 patients with advanced stage optimally cytoreduced epithelial ovarian cancer (median follow up 33months) were identified. 51% and 49% of patients received IV/IP and IV chemotherapy, respectively. 27%, 22%, and 39% of patients were of white, black, and other race. Compared with IV chemotherapy only, IV/IP chemotherapy was associated with longer OS (log rank <0.002) and IV/IP chemotherapy versus IV chemotherapy alone was associated with a lower risk of death (HR=0.31, 95% CI 0.16-0.62, P<0.001). The median overall survival for the IV/IP and IV groups was 76months (95% CI 62 - not estimated) and 38months (95% CI 30-55), respectively. There was a trend toward higher risk of death for patients who completed fewer than 6cycles of IV/IP chemotherapy compared to women who completed 6 IV/IP cycles (HR=3.2, 95% CI 0.98-9.27 (P=0.05). No differences in patient or tumor characteristics were identified between these two groups of patients. CONCLUSIONS: In our racially diverse urban patients, 50% of patients received IV/IP chemotherapy and it was associated with improved overall survival compared to IV chemotherapy alone. Further investigation is needed to identify barriers to use of IV/IP chemotherapy.

Phase II trial of adjuvant pelvic radiation "sandwiched" between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma.

OBJECTIVE: To evaluate the safety and survival in women treated with adjuvant pelvic radiation "sandwiched" between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. METHODS: Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m(2)) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. RESULTS: A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43-82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3 and 4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1 and 2 patients was 65.5 ± 3.6 months and 76.5 ± 4.3 months, respectively. PFS and OS for combined stage 3 and 4 patients was 25.8 ± 3.0 and 35.9 ± 5.3 months, respectively. Three-year % survival probability for stage 1 and 2 patients was 84% and for stage 3 and 4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. CONCLUSIONS: Compared to prior studies of single modality adjuvant therapy, RT "sandwiched" between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC.

Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma.

OBJECTIVE: Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin "sandwiched" with RT in patients with surgically staged and completely resected uterine carcinosarcoma. METHODS: Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m(2)/day×5 days) with cisplatin (20 mg/m(2)/day×5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m(2)/day×5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods. RESULTS: In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both 'sandwiched' with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p=0.16), so they were combined for analysis. 19 patients (70%) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 ± 1.12 months; log-rank p=0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 ± 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18%, 4% and 4% of cycles, respectively. CONCLUSIONS: Ifosfamide "sandwiched" with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this 'sandwich' regimen comes with a moderate but tolerable toxicity profile.