A B S T R A C T PurposeIntraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed. Patients and MethodsTreatment was as follows: paclitaxel 135 mg/m 2 IV over 3 hours day 1, cisplatin 75 mg/m 2 IP day 2, and paclitaxel 60 mg/m 2 IP day 8. Bevacizumab 15 mg/kg IV was given after paclitaxel on day 1 beginning in cycle 2. After six cycles of chemotherapy, bevacizumab was given every 3 weeks for 17 additional treatments. The primary end point was safety and tolerability determined by whether 60% of patients completed six cycles of IV/IP chemotherapy. ResultsOf 41 treated patients, 30 (73%) received six cycles of IV/IP chemotherapy and 35 (85%) received at least four cycles. Three (27%) of those who discontinued chemotherapy did so because of complications related to bevacizumab (hypertension, n ϭ 2; perforation, n ϭ 1). Grades 3 to 4 toxicities included neutropenia (34%), vasovagal syncope (10%), hypertension (7%), nausea/ vomiting (7%), hypomagnesemia (7%), and abdominal pain (7%). There were three grade 3 small bowel obstructions (7%) during cycles 3, 9, and 15. One patient died following rectosigmoid anastomotic dehiscence during cycle 4. Estimated median PFS is 28.6 months (95% CI, 19.1 to 38.9 months). Three patients (7%) had IP port malfunction. ConclusionThe addition of bevacizumab to this IP regimen is feasible; however, bevacizumab may increase the risk of bowel obstruction/perforation. The observed median PFS is similar to that seen with IP/IV chemotherapy alone.

5539 Background: IP cisplatin (Cis) plus IV/IP paclitaxel (Tax) is a standard therapy for optimally debulked ovarian cancer. Bevacizumab (Bev) is a recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor. Activity of Bev in recurrent ovarian cancer has been reported in phase II trials. In this study IP Cis and IV/IP Tax are combined with IV Bev as front-line therapy. Methods: Patients with optimal (<1 cm residual), FIGO stage II or III, epithelial ovarian, fallopian tube, or peritoneal cancer, acceptable organ function, and KPS ≥ 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev: Tax 135 mg/m2 IV over 3 hours on Day 1, Cis 75 mg/m2 IP on Day 2, Tax 60 mg/m2 IP on Day 8, Bev 15 mg/kg IV on Day 1 (starting cycle 2). Bev is continued every 3 weeks for 17 treatments after chemotherapy is complete. This study will enroll 41 patients. The primary endpoint is safety and tolerability, determined by whether at least 60% of patients complete the prescribed 6 cycles of cytotoxic chemotherapy without unacceptable toxicity. Results: Thirty-nine women [median age 56 (40–69)] have been treated on study: 26 (67%) completed 6 IV/IP cycles; 5 (13%) are receiving ongoing IV/IP treatment; 4 (10%) experienced IP port malfunction (3 finished 5 IV/IP cycles, 1 came off study for port revision); 3 (8%) switched from IP Cis to IV carboplatin due to grade 3 nephrotoxicity in cycle 1 (n = 2) or grade 3 hypertension in cycle 6 (n = 1); and 1 (2.5%) patient died following rectosigmoid anastomotic dehiscence during cycle 4. Grade 3/4 treatment-related toxicities include hypertension (10%), vasovagal events (10%), neutropenia (26%), nausea/vomiting (10%), and hypomagnesemia (8%). There were 3 occurrences of grade 3 abdominal pain (8%); and 3 adhesion-related grade 3 small bowel obstructions (8%), during cycles 3, 9, and 15, respectively. Conclusions: The addition of Bev to this IV/IP regimen appears to be feasible. Bev may increase the risk of small bowel obstruction/perforation in these patients. Enrollment continues and updated results will be presented. [Table: see text]

5523 Background: IP Cis plus IV/IP Tax is a standard therapy for optimally debulked ovarian cancer. Bev is a recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor (VEGF). Activity of Bev against recurrent ovarian cancer has been reported in phase II trials. In this study IP Cis and IV/IP Tax are combined with IV Bev as front-line therapy to assess safety and tolerability. Methods: Patients with optimal (<1 cm residual), FIGO stage II or III, epithelial ovarian, fallopian tube, or peritoneal cancer, acceptable organ function, and KPS = 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev (starting cycle 2): Tax 135 mg/m2 IV over 3 hours on Day 1, Cis 75 mg/m2 IP on Day 2, Tax 60 mg/m2 IP on Day 8, Bev 15 mg/kg IV on Day 1. Extended treatment with Bev is continued every 3 weeks for 17 treatments after chemotherapy is complete. The study will enroll 41 patients. The primary endpoint is safety and tolerability, determined by the proportion of patients who complete the prescribed 6 cycles of cytotoxic chemotherapy without discontinuation and without dose-limiting non-hematologic and non-electrolyte toxicity. A stopping rule will be applied if excessive toxicity is encountered. Results: To date, 8 women have been treated on the study. Median age: 53 (48–59). All 31 planned doses of chemotherapy have been administered in full. One dose of IP Tax was delayed for 2 days due to abdominal pain. One patient had her first dose of Bev delayed for 1 cycle due to surgical wound infection. There have been no toxicities > grade 3. Grade 1/2 toxicities include: fatigue (87.5%); nausea (50%); and hypomagnesemia (37.5%). Grade 3 toxicities per patient: fatigue (12.5%); hyponatremia (25%); hypokalemia (25%); hypertension (12.5%); abdominal pain (12.5%); and neutropenia (12.5%). Of the 5 patients with pretreatment CA125 >35 Units/mL, 4 normalized their value after 1 cycle of chemotherapy and 1 patient normalized after 2 cycles. Conclusions: Preliminary experience suggests that the combination of IV Bev with IP Cis plus IV/IP Tax may be well tolerated. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.