Format

Send to

Choose Destination
Gynecol Oncol. 2017 Mar;144(3):480-485. doi: 10.1016/j.ygyno.2017.01.008. Epub 2017 Jan 12.

Phase II trial of albumin-bound paclitaxel and granulocyte macrophage colony-stimulating factor as an immune modulator in recurrent platinum resistant ovarian cancer.

Author information

1
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.
2
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.
3
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.
4
Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, 850 Republican St, Seattle, WA 98195, United States.
5
Seattle Cancer Care Alliance, 825 Eastlake Ave. E., Seattle, WA 98109, United States.
6
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, United States.

Abstract

BACKGROUND:

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.

METHODS:

Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m2 days 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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Chemo-immunotherapy; GM-CSF; Myeloid derived suppressor cells; Nab-paclitaxel; Ovarian cancer

PMID:
28089377
DOI:
10.1016/j.ygyno.2017.01.008
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center