Impact of concomitant medication on recurrence, survival and tolerability of chemotherapy in early colon cancer patients - A post-hoc analysis of the PETACC 8 trial.

BACKGROUND: Only few information is available about the impact of concomitant medication (CM) and comorbidities on the outcome of cancer patients and the tolerability of chemotherapy. METHODS: Patients of the phase III randomized trial PETACC8 had resection with curative intent of a stage III colon cancer (CC) and were treated with standard adjuvant fluoropyrimidine and oxaliplatin + /- cetuximab over 6 months. Information on CM intake has been gathered by study visits at inclusion as well as during chemotherapy. We investigated the association between number of CM as well as the 5 most frequently applied CM categories according to the WHO ATC classification system (gastro-esophageal reflux disease (GERD) treatment, anticoagulants, platelet aggregation inhibitors, cardiovascular and antidiabetic drugs) with outcome and tolerability. RESULTS: Among 2559 patients, median number of CM intake was 8 (range 0-25), with only 22 patients (0.9 %) without any CM intake. Anticoagulation treatment was the only CM category being significantly and independently associated with a shorter disease-free survival (DFS) (HR 1.29, 95 %CI 1.06-1.56, p = 0.010) as well as overall survival (OS) (HR 1.28, 95 %CI 1.02-1.59, p = 0.032). No association of number of CM (<5,5-10,>10) has been observed neither with DFS (ref.;HR 0.98;HR 1.17) nor OS (ref.;HR 0.98;HR 1.15) (p > 0.05). Patients with anticoagulants experienced significantly more grade 3/4 adverse events (AEs) (75.9 % vs 64.8 %, p = 0.002) and treatment discontinuations due to toxicity (17.7 % vs 10.8 %, p = 0.005) compared to patients without anticoagulants. DISCUSSION: Early CC patients with polypharmacy do not generally exhibit an impaired outcome. Anticoagulation was the only CM category associated with a shorter DFS and OS which might be a consequence of enhanced toxicities necessitating treatment adaptations in these patients.