Provided are methods and compositions for prolonging survival and/or reducing or inhibiting tumor growth in a cancer subject receiving a regimen of one or more chemotherapeutic agents, an inhibitor of soluble epoxide hydrolase (sEHi) and a non-steroidal anti-inflammatory drug (NSAID) that inhibits one or more enzymes selected from the group consisting of cyclo-oxygenase (“COX”)-1, COX-2, and 5-lipoxygenase (“5-LOX”). The methods and compositions decrease toxicity and/or adverse side effects in subjects receiving a regimen of one or more chemotherapeutic agents.