Prognostic Impact of Early Treatment and Oxaliplatin Discontinuation in Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 11 Adjuvant Trials

Author(s): Claire Gallois, MD1; Qian Shi, PhD2; Jeffrey P. Meyers, MD2; Timothy Iveson, MD3; Steven R. Alberts, MD, MPH4; Aimery de Gramont, MD5; Alberto F. Sobrero, PhD6; Daniel G. Haller, MD7; Eiji Oki, MD8; Anthony Frank Shields, MD, PhD9; Richard M. Goldberg, MD10; Rachel Kerr, MD11; Sara Lonardi, MD12; Greg Yothers, PhD13; Caroline Kelly, PhD14; Ioannis Boukovinas, MD, PhD15; Roberto Labianca, MD16; Frank A. Sinicrope, MD4; Ioannis Souglakos, MD, PhD17; Takayuki Yoshino, MD18; Jeffrey A. Meyerhardt, MD, MPH19; Thierry André, MD, PhD20; Demetris Papamichael, MD21; and Julien Taieb, MD, PhD1
Source: DOI: 10.1200/JCO.21.02726 Journal of Clinical Oncology 41, no. 4 (February 01, 2023) 803-815.

Dr. Maen Hussein's Thoughts

Stopping oxaliplatinum and cont. of 5FU is better than stopping all chemotherapy. An option for patients with worsening neuropathy or other oxaliplatinum toxicity.

 

PURPOSE

Oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) for 6 months remains a standard in high-risk stage III patients. Data are lacking as to whether early discontinuation of all treatment (ETD) or early discontinuation of oxaliplatin (EOD) could worsen the prognosis.

MATERIALS AND METHODS

We studied the prognostic impact of ETD and EOD in patients with stage III CC from the ACCENT/IDEA databases, where patients were planned to receive 6 months of infusional fluorouracil, leucovorin, and oxaliplatin or capecitabine plus oxaliplatin. ETD was defined as discontinuation of treatment and EOD as discontinuation of oxaliplatin only before patients had received a maximum of 75% of planned cycles. Association between ETD/EOD and overall survival and disease-free survival (DFS) were assessed by Cox models adjusted for established prognostic factors.

RESULTS

Analysis of ETD and EOD included 10,447 (20.9% with ETD) and 7,243 (18.8% with EOD) patients, respectively. Compared with patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, with Eastern Cooperative Oncology Group performance status ≥ 1, and for ETD, older with a lower body mass index. In multivariable analyses, ETD was associated with a decrease in disease-free survival and overall survival (hazard ratio [HR], 1.61, P < .001 and HR, 1.73, P < .001), which was not the case for EOD (HR, 1.07, P = .3 and HR, 1.13, P = .1). However, patients who received < 50% of the planned cycles of oxaliplatin had poorer outcomes.

CONCLUSION

In patients treated with 6 months of oxaliplatin-based chemotherapy for stage III CC, ETD was associated with poorer oncologic outcomes. However, this was not the case for EOD. These data favor discontinuing oxaliplatin while continuing fluoropyrimidine in individuals with significant neurotoxicity having received > 50% of the planned 6-month chemotherapy.

Author Affiliations

1Paris‐Cité University, Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, SIRIC CARPEM, Paris, France; 2Department of Health Science Research, Mayo Clinic, Rochester, MN; 3Department of Medical Oncology, University of Southampton, Southampton, United Kingdom; 4Department of Oncology, Mayo Clinic, Rochester, MN; 5Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France; 6Medical Oncology, IRCCS San Martino IST, Genoa, Italy; 7Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA; 8Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 9Karmanos Cancer Institute, Wayne State University, Detroit, MI; 10West Virginia University Cancer Institute and the Mary Babb Randolph Cancer Center, Morgantown, WV; 11Department of Oncology, Oxford University, Oxford, United Kingdom; 12Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IRCCS, Padua, Italy; 13Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA; 14Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom; 15Bioclinic Thessaloniki Medical Oncology Unit, Thessaloniki, Greece; 16Ospdale Papa Giovanni XXIII, Bergamo, Italy; 17Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece; 18Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; 19Dana-Farber Cancer Institute, Boston, MA; 20Sorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France; 21Division of Medical Oncology, Bank Of Cyprus Oncology Centre, Nicosia, Cyprus

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