Refining the Use of Adjuvant Oxaliplatin in Clinical Stage II or III Rectal Adenocarcinoma.


Journal

The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837

Informations de publication

Date de publication:
08 2019
Historique:
received: 08 06 2018
accepted: 12 12 2018
pubmed: 31 1 2019
medline: 1 8 2020
entrez: 31 1 2019
Statut: ppublish

Résumé

Current guidelines include the use of adjuvant oxaliplatin in clinical stage II or III rectal adenocarcinoma. However, its efficacy is supported by a single phase II trial. We aimed to examine whether oxaliplatin confers survival benefit in this patient population. Using the National Cancer Database (2006-2013) we identified 6,868 individuals with clinical stage II or III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy. We used multivariate Cox regression to evaluate survival differences according to treatment intensity and change from clinical to pathological stage. We demonstrated an association with improved overall survival with the use of doublet adjuvant chemotherapy in pathological stage III rectal adenocarcinoma (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.92). This association was confirmed in patients with clinical stage III and subsequent pathological stage III disease (HR, 0.69; 95% CI, 0.57-0.83) and was not observed in patients who progressed from clinical stage II to pathological stage III disease. Doublet adjuvant chemotherapy was not associated with improved overall survival in patients with pathological stage 0 or I disease, regardless of their clinical stage. Adjuvant oxaliplatin following neoadjuvant chemoradiotherapy in rectal adenocarcinoma was confirmed in patients with clinical stage III and subsequent pathological stage III disease. Omission of oxaliplatin can be considered in pathological complete response or pathological stage I disease. Current guidelines include the use of oxaliplatin as part of adjuvant chemotherapy (AC) in patients with clinical stage II or III rectal adenocarcinoma (RAC). However, its efficacy is supported only by a single phase II trial. This study found an association with improved overall survival with the use of doublet AC in patients diagnosed with clinical stage III and subsequent pathological stage III, and not in patients with pathological stage 0 or I, regardless of their clinical stage. Therefore, omission of oxaliplatin can be considered in patients with either pathological complete response or pathological stage I RAC, thereby avoiding oxaliplatin-induced neuropathy.

Sections du résumé

BACKGROUND
Current guidelines include the use of adjuvant oxaliplatin in clinical stage II or III rectal adenocarcinoma. However, its efficacy is supported by a single phase II trial. We aimed to examine whether oxaliplatin confers survival benefit in this patient population.
METHODS
Using the National Cancer Database (2006-2013) we identified 6,868 individuals with clinical stage II or III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy. We used multivariate Cox regression to evaluate survival differences according to treatment intensity and change from clinical to pathological stage.
RESULTS
We demonstrated an association with improved overall survival with the use of doublet adjuvant chemotherapy in pathological stage III rectal adenocarcinoma (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.92). This association was confirmed in patients with clinical stage III and subsequent pathological stage III disease (HR, 0.69; 95% CI, 0.57-0.83) and was not observed in patients who progressed from clinical stage II to pathological stage III disease. Doublet adjuvant chemotherapy was not associated with improved overall survival in patients with pathological stage 0 or I disease, regardless of their clinical stage.
CONCLUSION
Adjuvant oxaliplatin following neoadjuvant chemoradiotherapy in rectal adenocarcinoma was confirmed in patients with clinical stage III and subsequent pathological stage III disease. Omission of oxaliplatin can be considered in pathological complete response or pathological stage I disease.
IMPLICATIONS FOR PRACTICE
Current guidelines include the use of oxaliplatin as part of adjuvant chemotherapy (AC) in patients with clinical stage II or III rectal adenocarcinoma (RAC). However, its efficacy is supported only by a single phase II trial. This study found an association with improved overall survival with the use of doublet AC in patients diagnosed with clinical stage III and subsequent pathological stage III, and not in patients with pathological stage 0 or I, regardless of their clinical stage. Therefore, omission of oxaliplatin can be considered in patients with either pathological complete response or pathological stage I RAC, thereby avoiding oxaliplatin-induced neuropathy.

Identifiants

pubmed: 30696723
pii: theoncologist.2018-0333
doi: 10.1634/theoncologist.2018-0333
pmc: PMC6693732
doi:

Substances chimiques

Oxaliplatin 04ZR38536J
Fluorouracil U3P01618RT

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e671-e676

Informations de copyright

© AlphaMed Press 2019.

Déclaration de conflit d'intérêts

Disclosures of potential conflicts of interest may be found at the end of this article.

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Auteurs

Ofer Margalit (O)

Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel ofer.margalit@sheba.health.gov.il.
Tel-Aviv University, Tel-Aviv, Israel.

Ronac Mamtani (R)

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Scott Kopetz (S)

University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Yu-Xiao Yang (YX)

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Yaacov R Lawrence (YR)

Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
Tel-Aviv University, Tel-Aviv, Israel.
Department of Radiation Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Samir Abu-Gazala (S)

Division of Transplantation, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Kim A Reiss (KA)

Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Talia Golan (T)

Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
Tel-Aviv University, Tel-Aviv, Israel.

Naama Halpern (N)

Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
Tel-Aviv University, Tel-Aviv, Israel.

Dan Aderka (D)

Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
Tel-Aviv University, Tel-Aviv, Israel.

Bruce Giantonio (B)

Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Einat Shacham-Shmueli (E)

Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
Tel-Aviv University, Tel-Aviv, Israel.

Ben Boursi (B)

Department of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
Tel-Aviv University, Tel-Aviv, Israel.
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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