Fasting Reduces the Incidence of Delayed-Type Vomiting Associated with Doxorubicin Treatment in Dogs with Lymphoma

Abstract

Fasting reduces gastrointestinal cellular proliferation rates through G1 cycle blockade and can promote cellular protection of normal but not cancer cells through altered cell signaling including down-regulation of insulin-like growth factor 1 (IGF-1). Consequently, the purpose of this study was to determine the effects of fasting on delayed-type chemotherapy-induced nausea and vomiting in dogs receiving doxorubicin. This prospective randomized crossover study involved intended administration of two doses of doxorubicin. Cancer-bearing dogs were randomized to be fasted for 24 hours beginning at 6 P.M. the night before the first or second doxorubicin administration, and all treatments were administered within an hour before or after 12 P.M. Dogs were fed normally before the alternate dose. Circulating IGF-1 concentrations were determined from serum samples obtained immediately before each doxorubicin treatment. Data from 35 doses were available from 20 dogs enrolled. Dogs that were fasted exhibited a significantly lower incidence of vomiting, when compared to fed dogs (10% compared to 67%, P = .020). Furthermore, among the 15 dogs that completed crossover dosing, vomiting was abrogated in four of five dogs that experienced doxorubicin-induced vomiting when fed normally (P = .050). No differences in other gastrointestinal, constitutional, or bone marrow toxicities or serum IGF-1 levels were observed.

Retrospective analysis of doxorubicin and prednisone as first-line therapy for canine B-cell lymphoma

“…However, both of these dogs were also documented to have progressive disease at this time as well, so it is challenging to elucidate retrospectively how lack of response to treatment may have played a role in the decision to euthanize when gastrointestinal signs secondary to DOX developed. Gastrointestinal toxicity is a common sequala of DOX administration, with up to 2/3 of dogs developing some degree of gastrointestinal toxicosis with < 15% of those considered severe to life-threatening [ 17 , 24 , 25 ]. .A fourth dog was euthanized after becoming septic after DOX-induced toxicity 9 days after treatment.…”

Gut microbiota modulation of chemotherapy efficacy and toxicity

“…Some evidence suggests that fasting might also minimize the adverse effects of some chemotherapies; for example, it has been shown to reduce the vomiting associated with doxorubicin treatment in dogs 76 . Although these approaches have yet to be extensively studied as diet-microbiota-chemotherapy interactions in cancer, data from human obesity and dietary studies clearly shows that the microbiota has a critical role in the modulation of cellular metabolism and the disease phenotype through both direct and indirect (for example SCFA, branched-chain amino acid metabolism and bile acids).…”

Protective effects of short-term dietary restriction in surgical stress and chemotherapy

“…The fasting-induced protection against otherwise lethal doses of the chemotherapeutic drugs has been demonstrated in vivo : fasting protects various mouse strains from high-dose etoposide toxicity (Raffaghello et al, 2008; Tinkum et al, 2015), protects CD-1 mice from high-dose doxorubicin (Lee et al, 2010), and protects FabplCre;Apc 15lox/+ mice against irinotecan induced weight loss, reduced activity, ruffled coat, hunched-back posture, diarrhea, and leukopenia (Huisman et al, 2015). Fasting reduces the delayed-type chemotherapy-induced nausea and vomiting in cancer-bearing dogs receiving doxorubicin (Withers et al, 2014). Analogously, the conditional liver-specific igf-1 gene deletion (LID) in transgenic mice, which results in a 70–80% reduction in circulating IGF-1 levels, results in the protection against cytotoxic chemotherapy drugs such as cyclophosphamide, doxorubicin and fluorouracil (Lee et al, 2010).…”