Background: Chemotherapy toxicity impacts dose intensity as well as temporarily deteriorating quality of life; some toxicity can be permanent, such as neuropathy. We previously demonstrated that fasting induces Differential Stress Resistance and hypothesized that fasting may protect normal host cells from chemotherapy toxicity, while potentially sensitizing cancer cells to chemotherapy. A low calorie, low protein fasting-mimicking diet (FMD) may be more acceptable than pure fasting. We are studying whether FMD will reduce chemotherapy toxicity and/or enhance efficacy. Changes in glucose and insulin‐like growth factor 1 (IGF1) may mediate or be biomarkers for the protective effects of fasting and will be studied in the trial population. Methods: Randomized phase II in 2 parallel cohorts (Prostate, n = 60, Breast n = 60). Treatment: Arm A = restricted diet consumed 3 days prior to and 24 hours after chemotherapy for 4 cycles. Arm B = regular diet. Eligibility: breast cancer with AC or TC in neoadjuvant setting, prostate cancer treated with Docetaxel, up-front or for mCRPC. BMI > 18.5. Exclusion: Diabetes Mellitus. Endpoints: Primary: Grade 2+ non-hematologic symptomatic toxicities experienced during 4 courses; additionally, radiographic (RECIST) response and PSA changes. Secondary: toxicity (all grade 2-4 events, dose reductions/delays) and efficacy (pathologic response for breast cancer, PSA/RECIST response for prostate cancer). Biomarker: plasma insulin, glucose, IGF1 and IGF binding protein (IGFBP) at baseline, and each cycle. Statistics: Proportion of patients with grade 2-4 symptomatic toxicities will be compared between treatment arms using stratified Mantel-Haenszel test; p-value ≤ 0.20 indicates the diet intervention is promising. With 60 patients in each cohort there is 88% power; initial analyses will evaluate breast/prostate cancer separately, yielding standard error no more than +/- 0.18 for estimates of the difference in the proportions of patients who experience a specific toxicity (or the composite). Quality of life will be assessed with SWOG questionnaire on day 1 of each chemotherapy cycle. Progress: 70 of 120 planned subjects have been accrued. Clinical trial information: NCT01802346