Post on 17-Dec-2015
transcript
Could fasting while receiving chemotherapy be beneficial?
18 July 2014
Michaela Onstad MD, MPHKristina Stemler PhD
Starvation-dependent differential stress resistance protects normal but not
cancer cells against high-dose chemotherapy
Lizzia Raffaghello, Changhan Lee, Fernando M. Safdie, Min Wei, Federica Madia, Giovanna Bianchi,
and Valter D. Longo
PNAS 2008
Quick Summary
• Aim – Constitutively active oncogenes prevent effective differential stress resistance
• Methods– Stress yeast, primary cancer cell lines with H2O2
and chemo after STS– Stress cancer-bearing mice and controls with
chemo after STS• Results (to come)• Where is the field now?
In vitro DSR to H2O2 treatment
Rat glioma cell line
Human glioma cell line Human neuroblastoma cell line
In vitro DSR to cyclophosphamide treatment
Human glioma cell line Human neuroblastoma cell line
CP treatment (15 mg/ml)
Fasting and cancer treatment in humans: A case series report
Fernando M. Safdie, Tanya Dorff, David Quinn, Luigi Fontana, Min Wei, Changan Lee, Pinchas Cohen,
and Valter D. Longo
Aging 2009
Quick Summary• Aim- Determine feasibility and effect of fasting in cancer patients
undergoing chemotherapy• Methods
– Descriptive case series– 10 patients with different malignancies– Voluntary fasting during chemotherapy– Reported side-effects– Effects on tumor volume, serum tumor markers
• Results– Fasting was well tolerated– Fasting was associated with reduced fatigue, weakness and GI side
effects– No adverse effects on tumor volume or serum tumor markers
Fasting Regimens
• Varied in length– 48-140 hours prior to chemotherapy– 5-56 hours following chemotherapy
• What was consumed during fasting was not well defined for most patients
• Diet during non-fasting chemotherapy cycles was not described
Other Reported Effects
• Complete blood count– Absolute neutrophil count– Hemoglobin– Platelets
• Tumor markers• Tumor size on imaging studies
Adverse Effects of Fasting
• No specific survey described to detect adverse side effects of fasting– “Minor complaints that arose during fasting included
dizziness, hunger, and headaches at a level that did not interfere with daily activities”
• Weight loss– “Weight lost during fasting was rapidly recovered in
most of the patients and did not lead to any detectable harm”
• Other measures of nutritional status?
Conclusions
• Fasting was well tolerated• Self-reported reduction in chemotherapy-
induced side effects• Fasting did not prevent chemotherapy-
induced reduction of tumor volume or tumor markers
Current trials
• Mayo Clinic (NCI)– All cancer types, goal recruitment 12 patients– Fast 24 hours before day 1 of course 2 of chemo. If well
tolerated, escalate fasting by 12 hours for each subsequent course for up to 3 courses in the absence of unacceptable toxicity
– Evaluate weight changes– Get a preliminary estimate of the longest fewasible
fasting perod prior to chemo– Evaluate toxicity profile of chemo during fasting– Evaluate changes in glucose, insulin, IGF1
Current Trials
• University of Southern California– Patients with advanced urothelial and pulmonary
malignancies (on gemcitabine, cisplatin)– Goal 70 patients– Groups
• Group I- patients fast for 24 hours prior to chemo• Group II- Fast for 48 hours prior to chemo• Group III- Fast for 72 hours prior to chemo• Group IV- Modified 48 hour fast with minimal caloric intake
– Evaluate toxicity, change in plasma markers
Current Trials
• Charite University, Berlin– 30 women with breast or ovarian cancer– Randomized controlled cross-over trial• Fast for 60-72 hours during the first half of a 4-6 cycle
regimen of chemo or fast for the same time period during the second half of chemo
– Evaluate QOL using FACT-O– Evaluate fatigue, intensity of adverse affects, and
laboratory assessments