title: Phase II study of intraperitoneal paclitaxel plus cisplatin and intravenous paclitaxel plus bevacizumab as adjuvant treatment of optimal stage II/III epithelial ovarian cancer.
abstract: OBJECTIVE
  Intraperitoneal (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.
  
  
  METHODS
  Treatment 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.
  
  
  RESULTS
  Of 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 = 2; perforation, n = 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.
  
  
  CONCLUSIONS
  The 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.
authors: Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. konnerj@mskcc.org
authors: Jason A
authors: JA
authors: Konner
authors: Diana M
authors: DM
authors: Grabon
authors: Scott R
authors: SR
authors: Gerst
authors: Alexia
authors: A
authors: Iasonos
authors: Howard
authors: H
authors: Thaler
authors: Sandra D
authors: SD
authors: Pezzulli
authors: Paul J
authors: PJ
authors: Sabbatini
authors: Katherine M
authors: KM
authors: Bell-McGuinn
authors: William P
authors: WP
authors: Tew
authors: Martee L
authors: ML
authors: Hensley
authors: David R
authors: DR
authors: Spriggs
authors: Carol A
authors: CA
authors: Aghajanian
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D000077216:Carcinoma, Ovarian Epithelial; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D017239:Paclitaxel; D002945:Cisplatin