title: Increased incidence of severe gastrointestinal events with first-line paclitaxel, carboplatin, and vorinostat chemotherapy for advanced-stage epithelial ovarian, primary peritoneal, and fallopian tube cancer.
abstract: OBJECTIVE
  We sought to assess the response rate and toxicity of paclitaxel, carboplatin, andvorinostat primary induction therapy for the treatment of advanced-stage ovarian carcinoma.
  
  
  METHODS
  Patients were treated with 6 cycles of weekly paclitaxel (80 mg/m), carboplatin (6 times area under the curve), and vorinostat (200 mg) every 28 days according to an institutional review board-approved protocol. The subjects were eligible for response evaluation; in patients who achieved stable disease or better following the conclusion of primary induction chemotherapy, they were subsequently treated with a planned 12 cycles of paclitaxel (135 mg/m) and vorinostat (400 mg) maintenance chemotherapy every 28 days.
  
  
  RESULTS
  Eighteen patients received a combined 90 cycles (median, 6 cycles; range, 1-6 cycles) of primary induction chemotherapy. Of the 18 subjects, 7 demonstrated a complete response, and 2 subjects exhibited a partial response (a total response rate of 50.0%). Eight patients also received a combined total of 50 cycles (median, 5 cycles; range, 1-12 cycles) of consolidation therapy. Grade 3/4 neutropenia and thrombocytopenia were observed in 9 (56.3%) and 2 (12.5%) patients. One patient (6.3%) developed grade 3 anemia, and another (6.3%) manifested a grade 3 neuropathy. Remarkably, we observed a significant gastrointestinal event (eg, bowel anastomotic perforation) in 3 patients, which effectuated the study's closure.
  
  
  CONCLUSIONS
  Because the current study was prematurely terminated, we cannot derive a conclusive assessment regarding the efficacy of this treatment. Nevertheless, the high incidence of severe gastrointestinal toxicity warrants further consideration when using vorinostat in the adjuvant setting for patients who have undergone a bowel resection as part of their initial tumor debulking.
authors: Gynecologic Oncology Associates, Newport Beach, CA, USA. bram@gynoncology.com
authors: Alberto A
authors: AA
authors: Mendivil
authors: John P
authors: JP
authors: Micha
authors: John V
authors: JV
authors: Brown
authors: Mark A
authors: MA
authors: Rettenmaier
authors: Lisa N
authors: LN
authors: Abaid
authors: Katrina L
authors: KL
authors: Lopez
authors: Bram H
authors: BH
authors: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D015994:Incidence; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D000077337:Vorinostat; D016190:Carboplatin; D017239:Paclitaxel