title: A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.
  
  
  METHODS
  Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m(2) on day 8. A standard 3+3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.
  
  
  RESULTS
  Patients were treated with paclitaxel 175 mg/m(2) IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m(2) IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), >2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m(2) IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).
  
  
  CONCLUSIONS
  Paclitaxel at 175 mg/m(2) IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m(2) IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.
authors.affiliation: Division of Gynecologic Oncology, Women's Cancer Center of Nevada, Las Vegas, NV 89169, USA. ngould@wccenter.com
authors.forename: Natalie
authors.initials: N
authors.lastname: Gould
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.forename: P H
authors.initials: PH
authors.lastname: Thaker
authors.forename: Paul
authors.initials: P
authors.lastname: Disilvestro
authors.forename: Steve
authors.initials: S
authors.lastname: Waggoner
authors.forename: S Diane
authors.initials: SD
authors.lastname: Yamada
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Armstrong
authors.forename: Lari
authors.initials: L
authors.lastname: Wenzel
authors.forename: Helen
authors.initials: H
authors.lastname: Huang
authors.forename: Paula M
authors.initials: PM
authors.lastname: Fracasso
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel