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?

Differential stress resistance against oxidants and genotoxins in yeast

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)

Short-term starvation protects against high dose etoposide, in vivo

DSR in cancer-bearing mice

Model for DSR in response to STS

Effect of diet on serum IGF-1 in murine models

Brandhorst et al., Exp Gerontology 2013

Fontana et al., Science 2010

Fontana et al., Science 2010

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

Cases

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

Measurement of Side Effects

Measurement of Side Effects

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

Further discussion

• What is the real world application, would patients be amenable?

• Can we utilize fasting induced chemoprotection in the clinic?– Weight loss goal or length of time?

• Current standard of care for diet during chemo?

• Risks related to fasting that should be considered?