3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome

N. Spry, J. Harvey, C. Macleod, M. Borg, S.Y. Ngan, J.L. Millar, P. Graham, Y. Zissiadis, A. Kneebone, S. Carroll, T. Davies, W.H.H. Reece, Barry Iacopetta, D. Goldstein

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Abstract

Purpose: The aim of this Phase 11 study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer.Methods and Materials: Patients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m(2) weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m(2)/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks.Results: For the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7%) and 7 (11.1%) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (RI 54.5%), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6% and 31.8%. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p <0.0001, respectively).Conclusions: This three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial. (c) 2008 Elsevier Inc.
Original languageEnglish
Pages (from-to)1438-1446
JournalInternational Journal of Radiation: Oncology - Biology - Physics
Volume70
Issue number5
DOIs
Publication statusPublished - 2008

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gemcitabine
chemotherapy
Pancreatic Neoplasms
radiation therapy
Radiotherapy
cancer
Drug Therapy
Fluorouracil
toxicity
Conformal Radiotherapy
Microsatellite Instability
Survival
Chemoradiotherapy
Head and Neck Neoplasms
microsatellites
metastasis
antigens
strata
Survival Rate
mutations

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Spry, N. ; Harvey, J. ; Macleod, C. ; Borg, M. ; Ngan, S.Y. ; Millar, J.L. ; Graham, P. ; Zissiadis, Y. ; Kneebone, A. ; Carroll, S. ; Davies, T. ; Reece, W.H.H. ; Iacopetta, Barry ; Goldstein, D. / 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome. In: International Journal of Radiation: Oncology - Biology - Physics. 2008 ; Vol. 70, No. 5. pp. 1438-1446.
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title = "3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome",
abstract = "Purpose: The aim of this Phase 11 study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer.Methods and Materials: Patients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m(2) weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m(2)/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks.Results: For the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7{\%}) and 7 (11.1{\%}) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (RI 54.5{\%}), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6{\%} and 31.8{\%}. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p <0.0001, respectively).Conclusions: This three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial. (c) 2008 Elsevier Inc.",
author = "N. Spry and J. Harvey and C. Macleod and M. Borg and S.Y. Ngan and J.L. Millar and P. Graham and Y. Zissiadis and A. Kneebone and S. Carroll and T. Davies and W.H.H. Reece and Barry Iacopetta and D. Goldstein",
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Spry, N, Harvey, J, Macleod, C, Borg, M, Ngan, SY, Millar, JL, Graham, P, Zissiadis, Y, Kneebone, A, Carroll, S, Davies, T, Reece, WHH, Iacopetta, B & Goldstein, D 2008, '3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome' International Journal of Radiation: Oncology - Biology - Physics, vol. 70, no. 5, pp. 1438-1446. https://doi.org/10.1016/j.ijrobp.2007.08.070

3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome. / Spry, N.; Harvey, J.; Macleod, C.; Borg, M.; Ngan, S.Y.; Millar, J.L.; Graham, P.; Zissiadis, Y.; Kneebone, A.; Carroll, S.; Davies, T.; Reece, W.H.H.; Iacopetta, Barry; Goldstein, D.

In: International Journal of Radiation: Oncology - Biology - Physics, Vol. 70, No. 5, 2008, p. 1438-1446.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 3D radiotherapy can be safely combined with sandwich systemic gemcitabine chemotherapy in the management of pancreatic cancer: factors influencing outcome

AU - Spry, N.

AU - Harvey, J.

AU - Macleod, C.

AU - Borg, M.

AU - Ngan, S.Y.

AU - Millar, J.L.

AU - Graham, P.

AU - Zissiadis, Y.

AU - Kneebone, A.

AU - Carroll, S.

AU - Davies, T.

AU - Reece, W.H.H.

AU - Iacopetta, Barry

AU - Goldstein, D.

PY - 2008

Y1 - 2008

N2 - Purpose: The aim of this Phase 11 study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer.Methods and Materials: Patients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m(2) weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m(2)/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks.Results: For the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7%) and 7 (11.1%) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (RI 54.5%), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6% and 31.8%. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p <0.0001, respectively).Conclusions: This three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial. (c) 2008 Elsevier Inc.

AB - Purpose: The aim of this Phase 11 study was to examine whether concurrent continuous infusion 5-fluorouracil (CI 5FU) plus three-dimensional conformal planning radiotherapy sandwiched between gemcitabine chemotherapy is effective, tolerable, and safe in the management of pancreatic cancer.Methods and Materials: Patients were enrolled in two strata: (1) resected pancreatic cancer at high risk of local relapse (postsurgery arm, n = 22) or (2) inoperable pancreatic cancer in head or body without metastases (locally advanced arm, n = 41). Gemcitabine was given at 1,000 mg/m(2) weekly for 3 weeks followed by 1 week rest then 5-6 weeks of radiotherapy and concurrent CI 5FU (200 mg/m(2)/day). After 4 weeks' rest, gemcitabine treatment was reinitiated for 12 weeks.Results: For the two arms combined, treatment-related Grade 3 and 4 toxicities were reported by 25 (39.7%) and 7 (11.1%) patients, respectively. No significant late renal or hepatic toxicity was observed. In the postsurgery arm (RI 54.5%), median time to progressive disease from surgery was 11.0 months, median time to failure of local control was 32.9 months, and median survival time was 15.6 months. The 1- and 2-year survival rates were 63.6% and 31.8%. No significant associations between outcome and mutations in K-ras or TP53 or microsatellite instability were identified. Post hoc investigation of cancer antigen 19-9 levels found baseline levels and increases postbaseline were associated with shorter survival (p = 0.0061 and p <0.0001, respectively).Conclusions: This three-dimensional chemoradiotherapy regimen is safe and promising, with encouraging local control for a substantial proportion of patients, and merits testing in a randomized trial. (c) 2008 Elsevier Inc.

U2 - 10.1016/j.ijrobp.2007.08.070

DO - 10.1016/j.ijrobp.2007.08.070

M3 - Article

VL - 70

SP - 1438

EP - 1446

JO - International Journal of Radiation Oncology : Biology : Physics

JF - International Journal of Radiation Oncology : Biology : Physics

SN - 0360-3016

IS - 5

ER -