Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma

P. Gibbs, C. Do, L. Lipton, D.N. Cade, M.J. Tapner, D. Price, G.D. Bower, R. Dowling, M. Lichtenstein, Guy Van Hazel

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    Abstract

    © 2015 Gibbs et al. Background: This prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma. Methods: Patients received yttrium-90-labelled (90Y) resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) as a single procedure on day 2 of the first weekly cycle of 5-fluorouracil (5FU; 600 mg/m2) with the option to switch to gemcitabine (1000 mg/m2) after 8 weeks of 5FU. Statistical analysis was conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA). The primary endpoint of the study was PFS in the liver, with a median of ≥16 weeks defined as the threshold for clinical significance. PFS and overall survival (OS) were summarised by the Kaplan-Meier method using non-parametric estimates of the survivor function. Results: Fourteen eligible patients were enrolled; ten had primary tumour in situ and eight had liver-only metastases. Patients received a median 90Y activity of 1.1 GBq and 8 weekly doses of 5FU; seven patients received a median of two doses of gemcitabine. Disease control in the liver was 93 % (two confirmed partial responses [PR], one unconfirmed PR, ten stable disease). Median reduction in cancer antigen 19-9 was 72 %. Median PFS was 5.2 months in the liver, which met the primary endpoint of the study, and 4.4 months at any site. PFS was prolonged in those with a resected primary compared with patients with primary in situ (median 7.8 vs. 3.4 months; p = 0.017). Median OS was 5.5 months overall and 13.6 months in patients with a resected primary. Grade 3/4 adverse events occurred in eight (57 %) patients during days 0-60. There was one sudden death and another patient who died from possible treatment-related liver failure 7.0 months after SIRT. Conclusions: SIRT and chemotherapy appears to be an effective treatment for liver metastases from pancreatic cancer, likely to be of most benefit in selected patients with a resected primary tumour and liver only disease. Significant toxicity was observed and the safety of this approach in patients with metastatic pancreatic cancer will need to be confirmed in subsequent studies. Further study is warranted with SIRT and modern chemotherapies. Trial registration:ACTRN12606000015549
    Original languageEnglish
    Pages (from-to)Article number 802
    JournalBMC Cancer
    Volume15
    DOIs
    Publication statusPublished - 2015

    Fingerprint

    Adenocarcinoma
    Radiotherapy
    Neoplasm Metastasis
    Drug Therapy
    Liver
    Disease-Free Survival
    gemcitabine
    Fluorouracil
    Pancreatic Neoplasms
    Yttrium
    Neoplasms
    Survival
    Liver Failure
    Sudden Death
    Microspheres
    Survivors
    Liver Diseases
    Therapeutics
    Safety
    Antigens

    Cite this

    Gibbs, P. ; Do, C. ; Lipton, L. ; Cade, D.N. ; Tapner, M.J. ; Price, D. ; Bower, G.D. ; Dowling, R. ; Lichtenstein, M. ; Van Hazel, Guy. / Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma. In: BMC Cancer. 2015 ; Vol. 15. pp. Article number 802.
    @article{1b009cac494a4f229dffcf7cdd29a9ca,
    title = "Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma",
    abstract = "{\circledC} 2015 Gibbs et al. Background: This prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma. Methods: Patients received yttrium-90-labelled (90Y) resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) as a single procedure on day 2 of the first weekly cycle of 5-fluorouracil (5FU; 600 mg/m2) with the option to switch to gemcitabine (1000 mg/m2) after 8 weeks of 5FU. Statistical analysis was conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA). The primary endpoint of the study was PFS in the liver, with a median of ≥16 weeks defined as the threshold for clinical significance. PFS and overall survival (OS) were summarised by the Kaplan-Meier method using non-parametric estimates of the survivor function. Results: Fourteen eligible patients were enrolled; ten had primary tumour in situ and eight had liver-only metastases. Patients received a median 90Y activity of 1.1 GBq and 8 weekly doses of 5FU; seven patients received a median of two doses of gemcitabine. Disease control in the liver was 93 {\%} (two confirmed partial responses [PR], one unconfirmed PR, ten stable disease). Median reduction in cancer antigen 19-9 was 72 {\%}. Median PFS was 5.2 months in the liver, which met the primary endpoint of the study, and 4.4 months at any site. PFS was prolonged in those with a resected primary compared with patients with primary in situ (median 7.8 vs. 3.4 months; p = 0.017). Median OS was 5.5 months overall and 13.6 months in patients with a resected primary. Grade 3/4 adverse events occurred in eight (57 {\%}) patients during days 0-60. There was one sudden death and another patient who died from possible treatment-related liver failure 7.0 months after SIRT. Conclusions: SIRT and chemotherapy appears to be an effective treatment for liver metastases from pancreatic cancer, likely to be of most benefit in selected patients with a resected primary tumour and liver only disease. Significant toxicity was observed and the safety of this approach in patients with metastatic pancreatic cancer will need to be confirmed in subsequent studies. Further study is warranted with SIRT and modern chemotherapies. Trial registration:ACTRN12606000015549",
    author = "P. Gibbs and C. Do and L. Lipton and D.N. Cade and M.J. Tapner and D. Price and G.D. Bower and R. Dowling and M. Lichtenstein and {Van Hazel}, Guy",
    year = "2015",
    doi = "10.1186/s12885-015-1822-8",
    language = "English",
    volume = "15",
    pages = "Article number 802",
    journal = "BMC Cancer",
    issn = "1471-2407",
    publisher = "BioMed Central",

    }

    Gibbs, P, Do, C, Lipton, L, Cade, DN, Tapner, MJ, Price, D, Bower, GD, Dowling, R, Lichtenstein, M & Van Hazel, G 2015, 'Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma' BMC Cancer, vol. 15, pp. Article number 802. https://doi.org/10.1186/s12885-015-1822-8

    Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma. / Gibbs, P.; Do, C.; Lipton, L.; Cade, D.N.; Tapner, M.J.; Price, D.; Bower, G.D.; Dowling, R.; Lichtenstein, M.; Van Hazel, Guy.

    In: BMC Cancer, Vol. 15, 2015, p. Article number 802.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Phase II trial of selective internal radiation therapy and systemic chemotherapy for liver-predominant metastases from pancreatic adenocarcinoma

    AU - Gibbs, P.

    AU - Do, C.

    AU - Lipton, L.

    AU - Cade, D.N.

    AU - Tapner, M.J.

    AU - Price, D.

    AU - Bower, G.D.

    AU - Dowling, R.

    AU - Lichtenstein, M.

    AU - Van Hazel, Guy

    PY - 2015

    Y1 - 2015

    N2 - © 2015 Gibbs et al. Background: This prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma. Methods: Patients received yttrium-90-labelled (90Y) resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) as a single procedure on day 2 of the first weekly cycle of 5-fluorouracil (5FU; 600 mg/m2) with the option to switch to gemcitabine (1000 mg/m2) after 8 weeks of 5FU. Statistical analysis was conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA). The primary endpoint of the study was PFS in the liver, with a median of ≥16 weeks defined as the threshold for clinical significance. PFS and overall survival (OS) were summarised by the Kaplan-Meier method using non-parametric estimates of the survivor function. Results: Fourteen eligible patients were enrolled; ten had primary tumour in situ and eight had liver-only metastases. Patients received a median 90Y activity of 1.1 GBq and 8 weekly doses of 5FU; seven patients received a median of two doses of gemcitabine. Disease control in the liver was 93 % (two confirmed partial responses [PR], one unconfirmed PR, ten stable disease). Median reduction in cancer antigen 19-9 was 72 %. Median PFS was 5.2 months in the liver, which met the primary endpoint of the study, and 4.4 months at any site. PFS was prolonged in those with a resected primary compared with patients with primary in situ (median 7.8 vs. 3.4 months; p = 0.017). Median OS was 5.5 months overall and 13.6 months in patients with a resected primary. Grade 3/4 adverse events occurred in eight (57 %) patients during days 0-60. There was one sudden death and another patient who died from possible treatment-related liver failure 7.0 months after SIRT. Conclusions: SIRT and chemotherapy appears to be an effective treatment for liver metastases from pancreatic cancer, likely to be of most benefit in selected patients with a resected primary tumour and liver only disease. Significant toxicity was observed and the safety of this approach in patients with metastatic pancreatic cancer will need to be confirmed in subsequent studies. Further study is warranted with SIRT and modern chemotherapies. Trial registration:ACTRN12606000015549

    AB - © 2015 Gibbs et al. Background: This prospective, open-label phase II study assessed the impact of liver-directed therapy with selective internal radiation therapy (SIRT) and systemic chemotherapy on progression-free survival (PFS) in liver-dominant metastatic pancreatic adenocarcinoma. Methods: Patients received yttrium-90-labelled (90Y) resin microspheres (SIR-Spheres; Sirtex Medical Limited, Sydney, Australia) as a single procedure on day 2 of the first weekly cycle of 5-fluorouracil (5FU; 600 mg/m2) with the option to switch to gemcitabine (1000 mg/m2) after 8 weeks of 5FU. Statistical analysis was conducted using Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA). The primary endpoint of the study was PFS in the liver, with a median of ≥16 weeks defined as the threshold for clinical significance. PFS and overall survival (OS) were summarised by the Kaplan-Meier method using non-parametric estimates of the survivor function. Results: Fourteen eligible patients were enrolled; ten had primary tumour in situ and eight had liver-only metastases. Patients received a median 90Y activity of 1.1 GBq and 8 weekly doses of 5FU; seven patients received a median of two doses of gemcitabine. Disease control in the liver was 93 % (two confirmed partial responses [PR], one unconfirmed PR, ten stable disease). Median reduction in cancer antigen 19-9 was 72 %. Median PFS was 5.2 months in the liver, which met the primary endpoint of the study, and 4.4 months at any site. PFS was prolonged in those with a resected primary compared with patients with primary in situ (median 7.8 vs. 3.4 months; p = 0.017). Median OS was 5.5 months overall and 13.6 months in patients with a resected primary. Grade 3/4 adverse events occurred in eight (57 %) patients during days 0-60. There was one sudden death and another patient who died from possible treatment-related liver failure 7.0 months after SIRT. Conclusions: SIRT and chemotherapy appears to be an effective treatment for liver metastases from pancreatic cancer, likely to be of most benefit in selected patients with a resected primary tumour and liver only disease. Significant toxicity was observed and the safety of this approach in patients with metastatic pancreatic cancer will need to be confirmed in subsequent studies. Further study is warranted with SIRT and modern chemotherapies. Trial registration:ACTRN12606000015549

    U2 - 10.1186/s12885-015-1822-8

    DO - 10.1186/s12885-015-1822-8

    M3 - Article

    VL - 15

    SP - Article number 802

    JO - BMC Cancer

    JF - BMC Cancer

    SN - 1471-2407

    ER -