Skip to main content
Top
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Safety and feasibility of fasting in combination with platinum-based chemotherapy

Authors: Tanya B. Dorff, Susan Groshen, Agustin Garcia, Manali Shah, Denice Tsao-Wei, Huyen Pham, Chia-Wei Cheng, Sebastian Brandhorst, Pinchas Cohen, Min Wei, Valter Longo, David I. Quinn

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients.

Methods

3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state.

Results

The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period.

Conclusion

Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting.

Trial registration

NCT00936364, registered propectively on July 9, 2009.
Appendix
Available only for authorised users
Literature
1.
go back to reference Appenroth D, Frob S, Kersten L, et al. Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats. Arch Toxicol. 1997;71:677–83.CrossRefPubMed Appenroth D, Frob S, Kersten L, et al. Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats. Arch Toxicol. 1997;71:677–83.CrossRefPubMed
2.
go back to reference DeMartinis BS, Bianchi MD. Effect of vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats. Pharmacol Res. 2001;44:317–20.CrossRef DeMartinis BS, Bianchi MD. Effect of vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats. Pharmacol Res. 2001;44:317–20.CrossRef
3.
go back to reference Yuce A, Atessahin A, Ceribasi AO, Aksakal M. Ellagic acid prevents cisplatin induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharm Toxicol. 2007;101:345–9.CrossRef Yuce A, Atessahin A, Ceribasi AO, Aksakal M. Ellagic acid prevents cisplatin induced oxidative stress in liver and heart tissue of rats. Basic Clin Pharm Toxicol. 2007;101:345–9.CrossRef
4.
go back to reference Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int J Cancer. 2008;123:1227–39.CrossRefPubMed Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int J Cancer. 2008;123:1227–39.CrossRefPubMed
5.
go back to reference Raffaghello L, Lee C, Safdie FM, et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci. 2008;105:8215-20. Raffaghello L, Lee C, Safdie FM, et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci. 2008;105:8215-20.
6.
go back to reference Csizsar A, Labinskyy N, Jimenez R, et al. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT-1. Mech Age Develop. 2009;130:518–27.CrossRef Csizsar A, Labinskyy N, Jimenez R, et al. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT-1. Mech Age Develop. 2009;130:518–27.CrossRef
7.
go back to reference Lee C, Raffaghello L, Brandhorst S, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012;4:124–7.CrossRef Lee C, Raffaghello L, Brandhorst S, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med. 2012;4:124–7.CrossRef
8.
go back to reference Mansell PI, Macdonald IA. The effect of starvation on insulin-induced glucose disposal and thermogenesis in humans. Metabolism. 1990;39:502–10.CrossRefPubMed Mansell PI, Macdonald IA. The effect of starvation on insulin-induced glucose disposal and thermogenesis in humans. Metabolism. 1990;39:502–10.CrossRefPubMed
9.
go back to reference Romijin JA, Godfried MH, Hommes MJT, et al. Decreased glucose oxidation during short-term starvation. Metabolism. 1990;39:525–30.CrossRef Romijin JA, Godfried MH, Hommes MJT, et al. Decreased glucose oxidation during short-term starvation. Metabolism. 1990;39:525–30.CrossRef
10.
go back to reference NgoTH BRJ, Tymchuk CN, et al. Effect of diet and exercise on serum insulin, IGF-1, and IGFBP-1 levels and growth of LNCaP Cells in Vitro. Cancer Causes Control. 2002;13:929–35.CrossRef NgoTH BRJ, Tymchuk CN, et al. Effect of diet and exercise on serum insulin, IGF-1, and IGFBP-1 levels and growth of LNCaP Cells in Vitro. Cancer Causes Control. 2002;13:929–35.CrossRef
11.
go back to reference O’Sullivan U, Gluckman PD, Breier BH, et al. Insulin-like growth factor-1 (IGF-1) in mice reduces weight loss during starvation. Endocrinology. 1989;125:2793–4.CrossRefPubMed O’Sullivan U, Gluckman PD, Breier BH, et al. Insulin-like growth factor-1 (IGF-1) in mice reduces weight loss during starvation. Endocrinology. 1989;125:2793–4.CrossRefPubMed
12.
go back to reference Muzumdar RH, Ma X, Fishman S, Yang X, Atzmon G, et al. Central and opposing effects of IGF-1 and IGF-binding protein-3 on systemic insulin action. Diabetes. 2006;55:2788–96.CrossRefPubMed Muzumdar RH, Ma X, Fishman S, Yang X, Atzmon G, et al. Central and opposing effects of IGF-1 and IGF-binding protein-3 on systemic insulin action. Diabetes. 2006;55:2788–96.CrossRefPubMed
13.
go back to reference Milman S, Atzmon G, Huffman DM, Wan J, Crandall JP, et al. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell. 2014;13:769–71.CrossRefPubMedPubMedCentral Milman S, Atzmon G, Huffman DM, Wan J, Crandall JP, et al. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell. 2014;13:769–71.CrossRefPubMedPubMedCentral
15.
go back to reference Olive PL, Wlodek D, Durand RE, Banath JP. Factors influencing DNA migration from individual cells subjected to gel electrophoresis. Exp Cell Res. 1992;198:259–67.CrossRefPubMed Olive PL, Wlodek D, Durand RE, Banath JP. Factors influencing DNA migration from individual cells subjected to gel electrophoresis. Exp Cell Res. 1992;198:259–67.CrossRefPubMed
16.
go back to reference Everitt AV, LeCouteur DG. Life extension by calorie restriction in humans. Ann NY Acad Sci. 2007;1114:428–33.CrossRefPubMed Everitt AV, LeCouteur DG. Life extension by calorie restriction in humans. Ann NY Acad Sci. 2007;1114:428–33.CrossRefPubMed
17.
go back to reference Dunn SE, Ehrlich M, Sharp NJH, et al. A dominant negative mutant of the insulin-like growth factor-1 receptor inhibits the adhesion, invasion and metastasis of breast cancer. Cancer Res. 1998;58:3353–61.PubMed Dunn SE, Ehrlich M, Sharp NJH, et al. A dominant negative mutant of the insulin-like growth factor-1 receptor inhibits the adhesion, invasion and metastasis of breast cancer. Cancer Res. 1998;58:3353–61.PubMed
18.
go back to reference Kritchevsky D. Diet and cancer: what’s next? J Nutr. 2003;133:3827S–9.PubMed Kritchevsky D. Diet and cancer: what’s next? J Nutr. 2003;133:3827S–9.PubMed
19.
go back to reference Lee C, Safdie FM, Raffaghello L, et al. Reduced levels of IGF-1 mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res. 2010;70:1564–72.CrossRefPubMedPubMedCentral Lee C, Safdie FM, Raffaghello L, et al. Reduced levels of IGF-1 mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res. 2010;70:1564–72.CrossRefPubMedPubMedCentral
20.
21.
go back to reference Chan JM, Gann PH, Giovannucci GL. Role of diet in prostate cancer development and progression. J Clin Oncol. 2005;23:8152–60.CrossRefPubMed Chan JM, Gann PH, Giovannucci GL. Role of diet in prostate cancer development and progression. J Clin Oncol. 2005;23:8152–60.CrossRefPubMed
22.
go back to reference Kjeldsen-Kragh J, Borchgrevink CF, Laerum E, et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet. 1991;338:899–902.CrossRefPubMed Kjeldsen-Kragh J, Borchgrevink CF, Laerum E, et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet. 1991;338:899–902.CrossRefPubMed
23.
go back to reference Varady KA, Hellerstein MK. Alternate day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr. 2007;86:7–13.PubMed Varady KA, Hellerstein MK. Alternate day fasting and chronic disease prevention: a review of human and animal trials. Am J Clin Nutr. 2007;86:7–13.PubMed
25.
go back to reference Ngo TH, Barnard RJ, Anton T, Tran C, Elashoff D, Heber D, et al. Effect of isocaloric low-fat diet on prostate cancer xenograft progression to androgen independence. Cancer Res. 2004;64:1252.CrossRefPubMed Ngo TH, Barnard RJ, Anton T, Tran C, Elashoff D, Heber D, et al. Effect of isocaloric low-fat diet on prostate cancer xenograft progression to androgen independence. Cancer Res. 2004;64:1252.CrossRefPubMed
26.
go back to reference Smith WJ, Underwood LE, Clemmons DR. Effects of caloric or protein restriction on insulin-like growth factor-1 (IGF-1) and IGF-binding protein in children and adults. J Clin Endocrinol Metab. 1995;80:443–9.PubMed Smith WJ, Underwood LE, Clemmons DR. Effects of caloric or protein restriction on insulin-like growth factor-1 (IGF-1) and IGF-binding protein in children and adults. J Clin Endocrinol Metab. 1995;80:443–9.PubMed
27.
go back to reference Cheng C-W, Adams GB, Perin L, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic stem cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014;14:810–23.CrossRefPubMedPubMedCentral Cheng C-W, Adams GB, Perin L, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic stem cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014;14:810–23.CrossRefPubMedPubMedCentral
Metadata
Title
Safety and feasibility of fasting in combination with platinum-based chemotherapy
Authors
Tanya B. Dorff
Susan Groshen
Agustin Garcia
Manali Shah
Denice Tsao-Wei
Huyen Pham
Chia-Wei Cheng
Sebastian Brandhorst
Pinchas Cohen
Min Wei
Valter Longo
David I. Quinn
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2370-6

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine