SAN FRANCISCO—Postoperative adjuvant chemotherapy is superior to standard oral fluoropyrimidine regimens in high-risk stage III colon cancer patients with advanced disease.
The ACTS-CC 02 trial was designed to verify the superiority of postoperative adjuvant chemotherapy with S-1/oxaliplatin (SOX) over tegafur and uracil (UFT) with leucovorin (UFT/LV), one of the standard oral fluoropyrimidine regimens in Japan. Previously, researchers showed the completion rate of adjuvant SOX and its incidence of adverse events were acceptable in patients with colon cancer.
At the 2018 Gastrointestinal Cancers Symposium, Takao Takahashi, MD, of the Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan, presented 3-year disease-free survival (DFS) data in 966 patients with high-risk stage III colon cancer, including any T, N2, or positive nodes around the origin of the feeding arteries (Abstract 484).
Patients underwent curative resection for pathologically confirmed high-risk stage III colon cancer. Then they were randomly assigned to receive either UFT/LV (300-600 mg/day of UFT according to body surface area and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80-120 mg/day of S-1 according to body surface area on days 1-14, every 21 days, 8 courses).
From April 2010 through October 2014, the 966 patients, median age 65 years, were enrolled at 260 institutions. The full analysis set, excluding patients who withdrew informed consent before protocol treatment, comprised 478 patients in the UFT/LV group and 477 patients in the SOX group. The vast majority (94%) of patients had ECOG PS of 0 and disease stage IIIB (50.2%) or stage IIIC (48.6%).
The results show a 3-year DFS rate of 60.6 percent in the UFT/LV group and 62.7 percent in the SOX group, demonstrating non-superiority of SOX over UFT/LV. In the stage IIIB group, the 3-year DFS rate was 69.3 percent in the UFT/LV group and 68.5 percent in the SOX group. In stage IIIC, the 3-year DFS rate was 50.6 percent and 55.8 percent in the UFT/LV group and SOX group, respectively.
“Notably, in the N2b subgroup, the 3-year DFS rate was 46 percent in the UFT/LV group and 54.7 percent in the SOX group,” said Takahashi.
In conclusion, he noted: “SOX was not shown to be superior to UFT/LV in patients with high-risk stage III colon cancer. However, the oxaliplatin-based regimen was suggested to be more effective in advanced disease, such as stage IIIC and N2b.”
Adjuvant Chemo for Peritoneal Metastases
In another presentation at the meeting, researchers examined the effectiveness of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal metastases.
Adjuvant HIPEC appears to be safe, with a low risk of perioperative morbidity and mortality, and regional therapy may provide a benefit to patients in the adjuvant setting. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay.
About one-quarter of patients with T4 or perforated colon cancer are at high risk of peritoneal metastases. “Sensitivity of imaging modalities for peritoneal metastases is limited and the majority of patients are diagnosed in a palliative setting. This provides a rationale for adjuvant HIPEC,” said Charlotte Emma Louise Klaver, MD, of Amsterdam UMC, University of Amsterdam, the Netherlands.
In a multicenter trial (Abstract 482), patients with T4 (either cT4 or pT4, N0-2, M0) or perforated colon cancer who underwent curative resection were randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy or to adjuvant systemic chemotherapy alone. Adjuvant HIPEC with oxaliplatin was performed simultaneously (9% of patients) or within 5-8 weeks (91% of patients) after the primary tumor resection. Patients without evidence of recurrent disease at 18 months based on CT imaging underwent diagnostic laparoscopy in both arms. The primary endpoint was peritoneal metastases-free survival at 18 months.
Between April 2015 and January 2017, 204 patients were randomized, 102 patients in the control arm and 102 patients in the experimental arm (two patients dropped out). Surgical exploration at the start of the HIPEC procedure revealed metastases in 11 patients (peritoneal metastases in 9 of 11 patients) in the experimental arm, and adjuvant HIPEC was not utilized.
Adjuvant systemic chemotherapy was administered in 89 of 100 eligible patients after a median of 6 weeks in the control arm and in 84 of 89 patients after 10 weeks in the experimental arm. The peritoneal metastases rate after completion of 18 months follow-up was 22 of 102 control patients and 18 of 100 experimental patients.
In the intent-to-treat analysis, no difference in 18-month peritoneal metastases-free survival was observed: 77 percent (control) versus 81 percent (experimental). Also, no differences were observed in 18-month DFS and overall survival. One patient developed encapsulating peritoneal sclerosis after HIPEC.
In conclusion, Klaver said: “Adjuvant HIPEC with oxaliplatin for patients with T4 or perforated colon cancer does not result in improved 18-month peritoneal metastases-free survival. Long-term results have to be awaited to assess the role of HIPEC in the adjuvant setting.”
Mark L. Fuerst is a contributing writer.
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