Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome

S. Dueland, A. H. Ree, K. K. Grøholt, M. G. Saelen, S. Folkvord, K. H. Hole, T. Seierstad, S. G. Larsen, K. E. Giercksky, J. N. Wiig, K. Boye, K. Flatmark

Research output: Contribution to journalArticle

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Abstract

Aims This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. Materials and methods Ninety-seven patients (57 T2–3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m2 day 1 and bolus 5-fluorouracil 500 mg/m2 and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. Results Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. Conclusions In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.

Original languageEnglish (US)
Pages (from-to)532-539
Number of pages8
JournalClinical Oncology
Volume28
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

oxaliplatin
Rectal Neoplasms
Neoplasms
Therapeutics
Neoadjuvant Therapy
Leucovorin
Chemoradiotherapy
Fluorouracil
Disease-Free Survival
Survival Rate
Radiation

Keywords

  • 5-fluorouracil
  • chemoradiotherapy
  • locally advanced rectal cancer
  • neoadjuvant chemotherapy
  • oxaliplatin

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer : Local Response, Toxicity and Long-term Outcome. / Dueland, S.; Ree, A. H.; Grøholt, K. K.; Saelen, M. G.; Folkvord, S.; Hole, K. H.; Seierstad, T.; Larsen, S. G.; Giercksky, K. E.; Wiig, J. N.; Boye, K.; Flatmark, K.

In: Clinical Oncology, Vol. 28, No. 8, 01.08.2016, p. 532-539.

Research output: Contribution to journalArticle

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title = "Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome",
abstract = "Aims This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. Materials and methods Ninety-seven patients (57 T2–3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m2 day 1 and bolus 5-fluorouracil 500 mg/m2 and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. Results Good histologic tumour regression was obtained in 72{\%} of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95{\%} of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61{\%} and 83{\%}, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. Conclusions In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.",
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T1 - Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer

T2 - Local Response, Toxicity and Long-term Outcome

AU - Dueland, S.

AU - Ree, A. H.

AU - Grøholt, K. K.

AU - Saelen, M. G.

AU - Folkvord, S.

AU - Hole, K. H.

AU - Seierstad, T.

AU - Larsen, S. G.

AU - Giercksky, K. E.

AU - Wiig, J. N.

AU - Boye, K.

AU - Flatmark, K.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Aims This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. Materials and methods Ninety-seven patients (57 T2–3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m2 day 1 and bolus 5-fluorouracil 500 mg/m2 and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. Results Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. Conclusions In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.

AB - Aims This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. Materials and methods Ninety-seven patients (57 T2–3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m2 day 1 and bolus 5-fluorouracil 500 mg/m2 and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. Results Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. Conclusions In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.

KW - 5-fluorouracil

KW - chemoradiotherapy

KW - locally advanced rectal cancer

KW - neoadjuvant chemotherapy

KW - oxaliplatin

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