Oxaliplatin Overused in Patients with Colon Cancer
San Francisco, CA—Oxaliplatin (Eloxatin) may be overused in the adjuvant treatment of colon cancer, based on
results of a survey of community-based oncologists and clinical investigators that was presented at the 2013 Gastrointestinal Cancers Symposium.
“Our results suggest that expectations for oxaliplatin benefit often exceed reality, and that oncologists may need to revisit the decision process,” said Kathryn Ziel, PhD, of Research To Practice in Miami, FL. “In a nutshell, oncologists may be using too much oxaliplatin. Given the toxicity profile, especially neurotoxicity that can persist for years, the decision to use adjuvant oxaliplatin should be made in the context of the actual benefit accrued to patients.”
Recent long-term clinical trial follow-up suggests that adding oxaliplatin to a fluoropyrimidine in the adjuvant treatment of colon cancer may provide less benefit than was originally believed. A recent report showed a lack of overall survival and disease-free survival benefits when oxaliplatin was added to the treatment regimen of 2246 patients with stage II colon cancer and elderly patients with colon cancer (Tournigand C, et al. J Clin Oncol. 2012;30:3353-3360).
“We wanted to document current usage of adjuvant chemotherapy and physician perceptions and practices in this regard,” Dr Ziel said.
Dr Ziel and colleagues recruited 25 clinical investigators specializing in gastrointestinal oncology and 77 practicing oncologists to complete a survey and provide data for 408 recent cases from their practices. Approximately 50% of the participants had ordered the 12-gene Oncotype DX Colon Cancer Assay to assist in decision-making.
The participants were asked, “What is the absolute benefit in recurrence risk reduction you believe is needed to justify using a fluoropyrimidine and oxaliplatin?” Their answer was a 5-year 5% reduction to use a fluoropyrimidine, and another 5% reduction to add oxaliplatin.
The investigators posed a number of hypothetical scenarios involving patients of various ages with different tumor burdens and disease characteristics, and participants had to estimate risk and say how they would treat these patients. Finally, they were queried about the last 3 patients they treated with stage II and stage III colon cancer.
The results showed that:
- Significant heterogeneity was evident in the treatment of a 60-year-old versus a 75-year-old patient. Not surprisingly, the use of oxaliplatin was less frequent for older patients, but 1 of 6 oncologists would choose this approach for a 75-year-old patient with a low-risk (T3N0M0) tumor
- For a higher-risk stage II tumor (T4N0M0), the oncologists estimated the risk of recurrence to be modestly different with and without treatment, and their predictions were in line with those derived from Adjuvant!Online
- For a stage III tumor with 2 positive nodes, the respondents correctly predicted a relatively substantial benefit that is similar to what is derived from Adjuvant!Online, but their estimates may not reflect recent long-term follow-up showing less benefit with oxaliplatin than previously believed
- When T stage increased, treatment preferences shifted dramatically toward a fluoropyrimidine plus oxaliplatin regimen, even for older patients; observation without treatment was infrequently used
- For grade 2 T4N0M0 patients, treatment was similar regardless of recurrence score, indicating that physicians have not embraced or are unaware of recent data showing that Oncotype DX can assist in deciding whether to include oxaliplatin for stage II and III diseases
- Consistent with predicted benefits, almost all participants recommended a fluoropyrimidine plus oxaliplatin regimen for both younger and older patients with 2 positive nodes.
Patients aged ≥70 years with stage II disease received considerably less intensive therapy. The majority of patients with stage III tumors received a fluorouracil/capecitabine regimen.
“The physicians wanted to see a 5% benefit in order to use oxaliplatin; in actuality, in stage II patients the benefit is only about 2%, according to Adjuvant!Online,” Dr Zeil noted.
“Roughly one third of the oncologists [36% of investigators and 29% of practicing oncologists] would treat a 60-year-old T3N0M0 patient with oxaliplatin,” Dr Zeil reported.
For T3N0M0 stage II tumors and for T4N0M0, patients aged >60 years were less likely to be prescribed oxaliplatin, “but we still saw that 17% would add oxaliplatin in the treatment of a T3N0M0 patient older than 60,” Dr Ziel added.
She suggested that the greater use of predictive assays will help physicians avoid using oxaliplatin in cases where its use is not justified.