Understanding FOLFOX Toxicity: Some Subsets Have Higher Risks

TON - March/April 2014 Vol 7 No 2 - Supportive Care
Caroline Helwick

Subsets of patients with colon cancer may benefit from increased surveillance for toxicities associated with adjuvant FOLFOX (leucovorin, fluorouracil, oxaliplatin) treatment, Canadian researchers suggest, based on their detailed analysis of the toxicity profile of this common regimen and their identification of factors that predict toxicity. They presented their findings at the 2014 Gastrointestinal Cancers Symposium, held January 16-18, in San Francisco, California.

The identification of patients with colon cancer at increased risk for side effects of adjuvant treatment allows clinicians to be more vigilant in preventing and managing these issues. “This enables the optimal delivery of chemotherapy,” said lead author Gillian Gresham, formerly of the University of Ottawa and now a doctoral candidate at Johns Hopkins University School of Public Health, Baltimore, Maryland.

The study sought to identify the key side effects associated with adjuvant FOLFOX in early colon cancer, and to look for their associations with clinical and patient-related factors.

The study included patients with stage III colon cancer treated at the 5 regional cancer centers of the British Columbia Cancer Agency. The researchers retrospectively reviewed the charts of 475 patients who received adjuvant FOLFOX. Their median age was 62 years, and 55% were male.

Renal, Cardiovascular, and Sensory Toxicities Were Common

The most common toxicities were abnormal kidney function (61.7%), neuropathy (54.9%), and cardiovascular-related side effects (hypertension, hypotension, thromboembolism, cardiac arrest; 51.4%). Gastrointestinal (GI) toxicities, including nausea, vomiting, and diarrhea, were recorded in 44% of patients.

Other common toxicities included anemia (76%), abnormal liver enzymes (61.7%), thrombocytopenia (28%), and neutropenia (27.8%).

In a multivariate analysis, renal dysfunction (glomerular filtration rate [GFR] <50) carried a 69% increased risk of any GI toxicity.

The risk of significant neutropenia was increased 2- to 3-fold among patients whose time between diagnosis and receipt of adjuvant chemotherapy exceeded 8 weeks; those with poor performance status; those older than 70 years; and patients with low white blood cell count (<6.4 x 109).

Interestingly, multiple toxicities were more prevalent among patients who waited more than 8 weeks to initiate adjuvant FOLFOX, Gresham added.

“It’s possible that patients who wait longer to initiate adjuvant therapy may already be sicker at baseline,” she said. “Neuropathy was interesting, because abnormal creatinine seemed to be predictive in both the univariate and multivariate models.”

Focus on GI Toxicities

The researchers also developed a 5-point scoring system to stratify patients into low- and high-risk groups for GI toxicity, based on baseline clinical factors. Low-risk patients (score 0-2) had a 45% risk for toxicity, whereas high-risk patients (score 3-5) had a 59% risk.

In the multivariate model for risk of any GI toxicity, age <70 years carried an odds ratio (OR) of 2.6 (P = .049); GFR <50 had an OR of 1.69 (P = .0038); and delayed time to adjuvant chemotherapy had an OR of 1.79 (P = .0059). Patients received 2 points each for delayed time to adjuvant treatment and poor GFR, and 1 point for advanced age. Gresham said that the scoring system could be useful, but it needs to be validated first.

Gresham suggested that considering important baseline characteristics—such as time to adjuvant treatment, advanced age, renal function, and certain laboratory parameters—when recommending adjuvant FOLFOX can be useful in identifying patients who are likely to experience serious side effects.

“We think this group of patients may benefit from increased monitoring in order to enable optimal doses of curative chemotherapy to be delivered,” she said. “Our recommendation would be to look for and recognize these characteristics at baseline. Monitor these patients more closely, and treat more proactively.”

Gresham G, Sidhu J, Malhi N, et al. Predicting toxicities from adjuvant treatment in a population-based cohort of early colon cancer (CC) patients (pts): a strategy to improve use of curative chemotherapy. J Clin Oncol. 2014;32(suppl 3):Abstract 412.

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Last modified: May 23, 2014