title: Phase II trial of albumin-bound paclitaxel and granulocyte macrophage colony-stimulating factor as an immune modulator in recurrent platinum resistant ovarian cancer.
abstract: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy.
  
  
  
  Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m2days 1, 8, 15 followed by GM-CSF 250μg days 16-26 every 28days for 6 planned cycles. The primary endpoint was remission duration compared to immediate prior remission. Peripheral blood was evaluated by flow cytometry and interferon-γ ELISPOT.
  
  
  
  Twenty-one patients were enrolled. Six patients (29%) achieved a biochemical complete response and 9 (43%) a partial response for an overall response rate of 72%. Median time to progression was 4months and 10% of patients achieved longer remissions than the immediate prior regimen. Median overall survival (OS) was 16.8months. Fewer myeloid derived suppressor cells (MDSC) at enrollment significantly associated with complete response (p=0.05). T-cell responses to IGF1R-p1332-1346 (r=0.827, p=0.0003) and IGF1R-p1242-1256 (r=0.850, p=0.0001) during treatment correlated with time to progression.
  
  
  
  Nab-paclitaxel combined with GM-CSF demonstrated biochemical responses in a majority of patients, although responses were not sustained. This combination did not demonstrate an advantage in OS over prior studies of nab-paclitaxel monotherapy. Agents that modulate MDSC should be studied as potential adjuvants to therapy. Strategies to expand T cells recognizing tumor-associated antigens biologically significant in ovarian cancer should also continue to be investigated.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, United States; Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States. Electronic address: johnliao@uw.edu.
authors.forename: John B
authors.initials: JB
authors.lastname: Liao
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, United States; Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States; Valley Medical Center, 400 South 43rd Street, Renton, WA 98055, United States.
authors.forename: Ron E
authors.initials: RE
authors.lastname: Swensen
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, United States; Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Kelsie J
authors.initials: KJ
authors.lastname: Ovenell
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, United States; Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Hitchcock-Bernhardt
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Reichow
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Minjun C
authors.initials: MC
authors.lastname: Apodaca
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Leonard
authors.initials: L
authors.lastname: D'Amico
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Childs
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Higgins
authors.affiliation: Seattle Cancer Care Alliance, 825 Eastlake Ave. E., Seattle, WA 98109, United States.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Buening
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, United States.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Goff
authors.affiliation: Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D007155:Immunologic Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017239:Paclitaxel
keywords: Chemo-immunotherapy; GM-CSF; Myeloid derived suppressor cells; Nab-paclitaxel; Ovarian cancer