title: Feasibility of interval cytoreduction following neoadjuvant chemotherapy with carboplatin, weekly paclitaxel, and bevacizumab for advanced ovarian cancer--a phase 1 study.
abstract: OBJECTIVE
  The objective of this study was to determine a dosing schedule of neoadjuvant chemotherapy using carboplatin, paclitaxel, and bevacizumab in women with advanced ovarian cancer, evaluating feasibility and outcomes from interval cytoreductive surgery (ICS).
  
  
  METHODS
  Using a "3+3" design, eligible patients received carboplatin (area under the curve, 5) and bevacizumab (15 mg/kg) every 3 weeks with escalating doses of weekly paclitaxel (60, 70, and 80 mg/m) for 3 cycles. Patients then received 1 cycle of chemotherapy without bevacizumab followed by ICS. The primary objective was to determine a feasible dosing schedule. Secondary objectives included defining toxicity, response rates based on imaging, and surgical outcomes defined by residual disease following ICS and 30-day postoperative outcomes.
  
  
  RESULTS
  Nine patients were enrolled with a median age of 64 years. There were no dose-limiting toxicities, and weekly paclitaxel 80 mg/m was deemed feasible. During chemotherapy treatment, there were a total of 7 attributable grade 3 toxicities, which most commonly included neutropenia and thromboembolism. All patients demonstrated a response on imaging before surgery, with a median reduction in disease of 56.4% (range, 36.9%-100%). Optimal ICS was performed in all patients, and 78% had no gross residual tumor. There were no intraoperative complications; however, 1 patient experienced an anastomotic leak (grade 4) 10 days after surgery requiring repeat operation.
  
  
  CONCLUSIONS
  A 4-cycle neoadjuvant regimen of carboplatin area under the curve of 5, weekly paclitaxel 80 mg/m, and bevacizumab 15 mg/kg for cycles 1 to 3, followed by interval cytoreduction, was feasible. Optimal ICS was achieved in all patients, and surgery was associated with acceptable morbidity.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Medical Center, Columbus, OH.
authors.forename: Ritu
authors.initials: R
authors.lastname: Salani
authors.forename: David M
authors.initials: DM
authors.lastname: O'Malley
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Copeland
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
authors.forename: Floor J
authors.initials: FJ
authors.lastname: Backes
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Fowler
authors.forename: Eric L
authors.initials: EL
authors.lastname: Eisenhauer
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000473:pathology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D010052:Ovariectomy; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel