NEW YORK (Reuters Health) Sep 09 - Adding oxaliplatin to a fluorouracil/leucovorin regimen for stage II or III colon cancer appears to cut younger patients' risk of death, according to an update from the National Surgical Adjuvant Breast and Bowel Project C-07 trial.
The first analysis of C-07, published in 2007 - and also the initial data from the MOSAIC trial, published in 2004 -- indicated that adding oxaliplatin to fluorouracil and leucovorin significantly improved disease-free survival (DFS).
Those two studies made oxaliplatin a standard part of adjuvant therapy for early-stage colon cancer, but there's been a persisting controversy over whether that regimen is universally appropriate for patients with stage II or III disease.
Results from MOSAIC suggested that the benefit of oxaliplatin for overall survival (OS) and DFS might be restricted to patients younger than age 70. A pooled analysis of data from MOSAIC and other trials suggested the same thing. The 2007 C-07 report didn't include any analyses of OS.
Fast forward to this summer, when study investigators published the updated C-07 data online August 22nd in the Journal of Clinical Oncology.
Exploratory analyses, with subjects stratified by age and disease stage, suggested "a robust effect of oxaliplatin for both DFS and OS in younger stage III patients," said lead author Dr. Greg Yothers of the University of Pittsburgh in email to Reuters Health.
"The benefit of oxaliplatin is less clear for unselected stage II patients," Dr. Yothers added, "and any true benefit may not outweigh the increased risk of toxicity, including persistent neuropathy."
He and his colleagues wrote, "In making treatment decisions for individual patients, we suggest that advanced age be one factor taken into account when oxaliplatin is being considered. We do not favor a rigid rule using chronologic age of older than 70 years to determine the use of oxaliplatin.... Consideration should be given to the patient's overall state of health and potential for tolerating adverse events."
The 2,409 patients in the C-07 study received either fluorouracil and leucovorin only, or those two drugs plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 of three eight-week treatment cycle.
Everyone in the study had either stage II (T3-4, N0, M0) or stage III (T1-4, N1-2, M0) colon cancer and had no evidence of residual malignant disease after surgical resection.
At a median follow-up of eight years, OS in the full study cohort did not differ significantly by treatment. Estimated five-year OS was 80.2% with oxaliplatin and 78.4% without it.
Adding oxaliplatin did significantly improve DFS in the full cohort (P = 0.002), consistent with the study's initial report.
The interactions between age (less than 70 years versus older) and treatment (with or without oxaliplatin) were significant. In patients younger than 70, the 5-year OS estimates were 81.8% with oxaliplatin and 78.8% without it (P=0.0733). For patients older than 70, however, five-year OS was lower with oxaliplatin (71.6% vs 76.3%, P=0.0391).
The authors suspect treatment-related toxicity was the cause of this difference in older patients, as they were more likely than younger patients to experience grade 4 or 5 toxicity on oxaliplatin.
The first analysis of C-07, published in 2007 - and also the initial data from the MOSAIC trial, published in 2004 -- indicated that adding oxaliplatin to fluorouracil and leucovorin significantly improved disease-free survival (DFS).
Those two studies made oxaliplatin a standard part of adjuvant therapy for early-stage colon cancer, but there's been a persisting controversy over whether that regimen is universally appropriate for patients with stage II or III disease.
Results from MOSAIC suggested that the benefit of oxaliplatin for overall survival (OS) and DFS might be restricted to patients younger than age 70. A pooled analysis of data from MOSAIC and other trials suggested the same thing. The 2007 C-07 report didn't include any analyses of OS.
Fast forward to this summer, when study investigators published the updated C-07 data online August 22nd in the Journal of Clinical Oncology.
Exploratory analyses, with subjects stratified by age and disease stage, suggested "a robust effect of oxaliplatin for both DFS and OS in younger stage III patients," said lead author Dr. Greg Yothers of the University of Pittsburgh in email to Reuters Health.
"The benefit of oxaliplatin is less clear for unselected stage II patients," Dr. Yothers added, "and any true benefit may not outweigh the increased risk of toxicity, including persistent neuropathy."
He and his colleagues wrote, "In making treatment decisions for individual patients, we suggest that advanced age be one factor taken into account when oxaliplatin is being considered. We do not favor a rigid rule using chronologic age of older than 70 years to determine the use of oxaliplatin.... Consideration should be given to the patient's overall state of health and potential for tolerating adverse events."
The 2,409 patients in the C-07 study received either fluorouracil and leucovorin only, or those two drugs plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 of three eight-week treatment cycle.
Everyone in the study had either stage II (T3-4, N0, M0) or stage III (T1-4, N1-2, M0) colon cancer and had no evidence of residual malignant disease after surgical resection.
At a median follow-up of eight years, OS in the full study cohort did not differ significantly by treatment. Estimated five-year OS was 80.2% with oxaliplatin and 78.4% without it.
Adding oxaliplatin did significantly improve DFS in the full cohort (P = 0.002), consistent with the study's initial report.
The interactions between age (less than 70 years versus older) and treatment (with or without oxaliplatin) were significant. In patients younger than 70, the 5-year OS estimates were 81.8% with oxaliplatin and 78.8% without it (P=0.0733). For patients older than 70, however, five-year OS was lower with oxaliplatin (71.6% vs 76.3%, P=0.0391).
The authors suspect treatment-related toxicity was the cause of this difference in older patients, as they were more likely than younger patients to experience grade 4 or 5 toxicity on oxaliplatin.
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