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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
Authors:Gould Natalie  Sill Michael W  Mannel Robert S  Thaker P H  Disilvestro Paul  Waggoner Steve  Yamada S Diane  Armstrong Deborah K  Wenzel Lari  Huang Helen  Fracasso Paula M  Walker Joan L
Institution:
  • a Division of Gynecologic Oncology, Women's Cancer Center of Nevada, Las Vegas NV 89169, USA
  • b Gynecologic Oncology Group Statistical and Data Center, Buffalo NY 14263, USA
  • c Division of Gynecologic Oncology, University of Oklahoma, OK 73190, USA
  • d Division of Gynecologic Oncology, Washington University, St Louis, MO 63110, USA
  • e Division of Gynecologic Oncology, Women and Infants Hospital, Providence RI 02905, USA
  • f Division of Gynecologic Oncology, Case Western Reserve University, Cleveland, OH 44106, USA
  • g Section of Gynecologic Oncology, University of Chicago, Chicago IL 60637, USA
  • h Gynecology and Obstretrics, Johns Hopkins Oncology Center, Baltimore, MD 21231, USA
  • i Center for Health Policy Research, University of California, Irvine, Irvine, CA 92697, USA
  • j Department of Medicine and the UVA Cancer Center, University of Virginia, Charlottesville VA 22908, USA
  • 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/m2 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/m2 IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m2 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/m2 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/m2 IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m2 IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.
    Keywords:Phase I trial  Intraperitoneal chemotherapy  Carboplatin  Paclitaxel  Ovarian cancer
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