Omega 3 (Eicosapentaenoic Acid and Others)

To explore the safety and effectiveness of omega-3 poly-unsaturated fatty acid (PUFA) added to parenteral nutrition in protecting patients with leukemia from severe enterocolitis

Fourteen patients with acute myeloid leukemia (AML) who received omega-3 PUFA in a phase II trial were compared with 66 consecutive control patients not getting this intervention. Total parenteral nutrition (TPN) was given as a standard emulsion containing the full supply of carbohydrates, amino acids, and lipids, with a total energy content of 2,215 kcal in a 1,875 mL volume via central venous catheter over 24 hours. Patients included in the phase II study additionally were administered 100 mL/d of a commercially available IV omega-3 PUFA formulation over four hours. TPN and omega-3 PUFA were given up to duration of four weeks.

• N = 14  
• AGE: Unknown
• MALES, FEMALES: Unknown
• KEY DISEASE CHARACTERISTICS: De novo AML or high-risk myelodysplastic syndrome (MDS); planning to undergo chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Eligible participants were any adults with cyto- or histopathologically confirmed de novo diagnosis of either AML or high-risk MDS (IPSS score of higher than 1.5). All participants had been considered for TPN and had an Eastern Cooperative Oncology Group performance status of 2 or less and were about to undergo myeloablative induction chemotherapy.

• SITE: Single site   
• SETTING TYPE: Inpatient   
• LOCATION: Bern, Switzerland

• PHASE OF CARE: Active antitumor treatment

• Phase II trial with a historical control group of consecutive patients with AML

• Common Terminology Criteria for Adverse Events (CTCAE) v3.0

Two out of 14 patients included in the phase II trial experienced grade 3 colitis after initiation of chemotherapy (14%), and none experienced grades 4 or 5. Conversely, 16 out of 66 control patients experienced grade 3 colitis (24%), 3 experienced grade 4 (5%), and 2 died of grade 5 colitis (3%). According to blind assessments, 3 out of 14 patients included in the phase II trial experienced grade 3 colitis after initiation of chemotherapy (21%), and 1 had grade 4 colitis (7%), whereas 7 out of 66 control patients experienced grade 3 colitis (11%), 4 experienced grade 4 (6%), and 4 died of grade 5 colitis (6%). Among the 13 patients who actually received omega-3 PUFA, two were deemed to have grade 3 colitis (15%) according to open assessment, whereas three were deemed to have grade 3 colitis (23%) and one was deemed to have grade 4 colitis (8%) according to blind assessment. Odds ratios of colitis were grades 3 and above. The benefit of omega-3 PUFA was more pronounced in adjusted as compared with crude analyses and more pronounced according to open as compared with blind assessments. Formal statistical significance at the conventional α level of 0.05 was reached only for the adjusted analyses of colitis grades as determined by the open assessor, with an odds ratio of 0.27 (95% CI 0.11–0.65). The IPT weighted analysis according to blind assessments yielded a non-significant odds ratio of 0.79 (95% CI 0.35–1.78).

The study showed little evidence to suggest that the addition of omega-3 PUFA to TPN in patients with AML undergoing myeloablative chemotherapy is effective in reducing the incidence of severe neutropenic enterocolitis. Results depended on the approach chosen in assessing colitis grades (open versus blind assessment), and the nature of the analysis (crude or adjusted using inverse probability of treatment weighting).

• Small sample (less than 30)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Questionable protocol fidelity
• Other limitations/explanation: The original study design was not carried out because of accrual problems.

Therapeutic interventions remain limited in neutropenic colitis. To truly answer the question of whether this intervention would benefit patients, trials should be centrally randomized with adequate placebo controls to blind patients, blind adjudication of colitis grades, and an intention-to-treat analysis.