Abstract
Purpose
The aim of this review was to analyze the potential effect of the nutritional support (oral supplementation/counseling, tube feeding, parenteral nutrition) combined with chemotherapy on long-term survival of cancer patients.
Methods
Using various electronic databases, we retrieved all English language papers on the combination nutritional support and chemotherapy and including data on long-term survival.
Results
29 trials (4 non-RCT) were retrieved. No significant benefit was observed except for a longer survival in a few selected subgroups of patients, depending on the tumor stage and compliance with the nutritional support. However, no study included survival as primary endpoint or was adequately powered for this purpose, and patients were seldom affected by malnutrition, a condition which would have made them extremely vulnerable and unsafe during an intensive chemotherapy with significant gastrointestinal toxicity. Finally, nutritional regimens were often inappropriate as regards quality and quantity of nutrients or too similar in the two arms of the trial to expect a result.
Conclusion
From the review of these trials, it appears clear that there is absence of evidence more than evidence of absence of effect of the supplemental nutritional support. This poor scenario should not discourage future large multicenter trials to assess the potential of an early versus a delayed support in mildly malnourished patients. From the practical point of view, a nutritional supplementation should be considered when severe malnutrition caused by the disease or following repeated oncologic treatments can make the patients poorly compliant with further chemotherapy cycles, as recommended by the international guidelines.
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References
Schwartz GF, Green HL, Bendon ML et al (1971) Combined parenteral hyperalimentation and chemotherapy in the treatment of disseminated solid tumors. Am J Surg 121:169–173. https://doi.org/10.1016/0002-9610(71)90095-x
Brandhorst S, Harputlugil E, Mitchell JR, Longo VD (2017) Protective effects of short-term dietary restriction in surgical stress and chemotherapy. Ageing Res Rev 39:68–77. https://doi.org/10.1016/j.arr.2017.02.001
Bozzetti F, Stanga Z (2020) Does nutrition for cancer patients feed the tumour? A clinical perspective. Crit Rev Oncol Hematol 153:103061. https://doi.org/10.1016/j.critrevonc.2020.103061
Baldwin C, Spiro A, McGough C et al (2011) Simple nutritional intervention in patients with advanced cancers of the gastrointestinal tract, non-small cell lung cancers or mesothelioma and weight loss receiving chemotherapy: a randomised controlled trial. J Hum Nutr Diet 24(5):431–440. https://doi.org/10.1111/j.1365-277X.2011.01189.x
Bourdel-Marchasson I, Blanc-Bisson C, Doussau A et al (2014) Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: a two-year randomized controlled trial. PLoS ONE 9(9):e108687. https://doi.org/10.1371/journal.pone.0108687
Cox S, Powell C, Carter B et al (2016) Role of nutritional status and intervention in oesophageal cancer treated with definitive chemoradiotherapy: outcomes from SCOPE1. Br J Cancer 115:172–177. https://doi.org/10.1038/bjc.2016.129
Dobrila-Dintinjana R, Trivanovic D, Zelic M et al (2013) Nutritional support in patients with colorectal cancer during chemotherapy: does it work. Hepatogastroenterology 60:475–480
Evans WK, Nixon DW, Daly JM et al (1987) A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer. J Clin Oncol 5(1):113–124. https://doi.org/10.1200/JCO.1987.5.1.113
Furness K, Silvers MA, Savva J et al (2017) Long-term follow-up of the potential benefits of early nutritional intervention in adults with upper gastrointestinal cancer: a pilot randomised trial. Support Care Cancer 25:3587–3593. https://doi.org/10.1007/s00520-017-3789-2
Klek S, Scislo L, Walewska E et al (2017) Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: a randomized, controlled trial. Nutrition 36:46–53. https://doi.org/10.1016/j.nut.2016.03.016
Orell H, Schwab U, Saarilahti K et al (2019) Nutritional counseling for head and neck cancer patients undergoing (chemo) radiotherapy-a prospective randomized trial. Front Nutr 18(6):22. https://doi.org/10.3389/fnut.2019.00022
Ovesen L, Allingstrup L, Hannibal J et al (1993) Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study. J Clin Oncol 11:2043–2049. https://doi.org/10.1200/JCO.1993.11.10.2043
Persson CR, Johansson BB, Sjöden PO et al (2002) A randomized study of nutritional support in patients with colorectal and gastric cancer. Nutr Cancer 42(1):48–58. https://doi.org/10.1207/S15327914NC421_7
Ravasco P, Monteiro-Grillo I, Camilo M (2012) Individualized nutrition intervention is of major benefit to colorectal cancer patients: long-term follow-up of a randomized controlled trial of nutritional therapy. Am J Clin Nutr 96:1346–1353. https://doi.org/10.3945/ajcn.111.018838
Scislo L, Pach R, Nowak A et al (2018) The impact of postoperative enteral immunonutrition on postoperative complications and survival in gastric cancer patients - randomized clinical trial. Nutr Cancer 70:453–459. https://doi.org/10.1080/01635581.2018.1445770
Trépanier M, Minnella EM, Paradis T et al (2019) Improved disease-free survival after prehabilitation for colorectal cancer surgery. Ann Surg 270:493–501. https://doi.org/10.1097/SLA.0000000000003465
van der Werf A, Langius JAE, Beeker A et al (2020) The effect of nutritional counseling on muscle mass and treatment outcome in patients with metastatic colorectal cancer undergoing chemotherapy: a randomized controlled trial. Clin Nutr 39:3005–3013. https://doi.org/10.1016/j.clnu.2020.01.009
Ho YW, Yeh KY, Hsueh SW, Hung CY, Lu CH, Tsang NM, Wang HM, Hung YS, Chou WC (2020) Impact of early nutrition counseling in head and neck cancer patients with normal nutritional status. Support Care Cancer. https://doi.org/10.1007/s00520-020-05804-3
Gogos CA, Ginopoulos P, Salsa B et al (1998) Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Cancer. 82:395–402. https://doi.org/10.1002/(sici)1097-0142(19980115)82:2%3c403::aid-cncr21%3e3.0.co;2-1
Fearon KC, Barber MD, Moses AG et al (2006) Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia. J Clin Oncol 24:3401–3407. https://doi.org/10.1200/JCO.2005.04.5724
Murphy RA, Mourtzakis M, Chu QS et al (2011) Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer 117:3774–3780. https://doi.org/10.1002/cncr.25933
Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, Giacosa A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ (2003) Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 52(10):1479–1486. https://doi.org/10.1136/gut.52.10.1479
Jatoi A, Rowland K, Loprinzi CL, Sloan JA, Dakhil SR, MacDonald N, Gagnon B, Novotny PJ, Mailliard JA, Bushey TI, Nair S, Christensen B, North Central Cancer Treatment Group (2004) An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. J Clin Oncol 22(12):2469–76. https://doi.org/10.1200/JCO.2004.06.024
Sánchez-Lara K, Turcott JG, Juárez-Hernández E et al (2014) Effects of an oral nutritional supplement containing eicosapentaenoic acid on nutritional and clinical outcomes in patients with advanced non-small cell lung cancer: randomised trial. Clin Nutr 33:1017–1023. https://doi.org/10.1016/j.clnu.2014.03.006
Laviano A, Calder PC, Schols A et al (2020) Targeted medical nutrition in pre-cachectic patients with non-small-cell lung cancer: a subgroup analysis. Nutr Cancer 1–2. https://doi.org/10.1080/01635581.2020.1773873
Boisselier P, Kaminsky MC, Thézenas S, Galloch, et al (2020) A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX. Am J Clin Nutr. nqaa227. https://doi.org/10.1093/ajcn/nqaa227
Bouleuc C, Anota A, Cornet C et al (2020) Impact on health-related quality of life of parenteral nutrition for patients with advanced cancer cachexia: results from a randomized controlled trial. Oncologist 25(5):e843–e851. https://doi.org/10.1634/theoncologist.2019-0856
Clamon GH, Feld R, Evans WK et al (1985) Effect of adjuvant central IV hyperalimentation on the survival and response to treatment of patients with small cell lung cancer: a randomized trial. Cancer Treat Rep 69:167–177
De Waele E, Mattens S, Honoré PM et al (2015) Nutrition therapy in cachectic cancer patients. The Tight Caloric Control (TiCaCo) pilot trial. Appetite 91:298–301. https://doi.org/10.1016/j.appet.2015.04.049
Jordan WM, Valdivieso M, Frankmann C et al (1981) Treatment of advanced adenocarcinoma of the lung with ftoratur, doxorubicin, cyclophosphamide, and cisplatin (FACP) and intensive IV hyperalimentation. Cancer Treat Rep 65:197–205
Levine AS, Brennan MF, Ramu A et al (1982) Controlled clinical trials of nutritional intervention as an adjunct to chemotherapy, with a comment on nutrition and drug resistance. Cancer Res 42(Supp1):774s–778s
Nixon DW, Moffitt S, Lawson DH et al (1981) Total parenteral nutrition as an adjunct to chemotherapy of metastatic colorectal cancer. Cancer Treat Rep 65(Suppl 5):121–128
Popp MB, Fisher RI, Simon RM et al (1981) A prospective randomized study of adjuvant parenteral nutrition in the treatment of diffuse lymphoma: effect on drug tolerance. Cancer Treat Rep 65(suppl 5):129–135
Popp MB, Fisher RI, Wesley R et al (1981) A prospective randomized study of adjuvant parenteral nutrition in the treatment of advance diffuse lymphoma: Influence on survival. Surgery 90:195–203
Samuels ML, Selig DE, Ogden S et al (1981) Iv hyperalimentation and chemotherapy for stage III testicular cancer: a randomized study. Cancer Treat Rep 65(7–8):615–627
Shamberger RC, Brennan MF, Goodgame JT et al (1984) A prospective, randomized study of adjuvant parenteral nutrition in the treatment of sarcomas: results of metabolic and survival studies. Surgery 96:1–12
Valdivieso M, Bodey GP, Benjamin RS et al (1981) Role of intravenous hyperalimentation as an adjunct to intensive chemotherapy for small cell bronchogenic carcinoma. Cancer Treat Rep 65(Suppl5):145–150
Weiner RS, Kramer BS, Clamon GH et al (1985) Effects of intravenous hyperalimentation during treatment in patients with small-cell lung cancer. J Clin Oncol 3:949–957
Bozzetti F (2020) Chemotherapy-induced sarcopenia. Curr Treat Options Oncol 21(1):7. https://doi.org/10.1007/s11864-019-0691-9
Altman DG, Bland JM (1995) Absence of evidence is not evidence of absence. BMJ 311(7003):485. https://doi.org/10.1136/bmj.311.7003.485
Bozzetti F, Forbes A (2009) The ESPEN clinical practice Guidelines on Parenteral Nutrition: present status and perspectives for future research. Clin Nutr 28:359–364. https://doi.org/10.1016/j.clnu.2009.05.010
Freedman B (1987) Equipoise and the ethics of clinical research. N Engl J Med 317(3):141–145. https://doi.org/10.1056/NEJM198707163170304
Liu W, Qdaisat A, Lee E et al (2019) The association between weight stability and parenteral nutrition characteristics and survival in patients with colorectal cancer. Gastroenterol Rep (Oxf) 7(6):419–425. https://doi.org/10.1093/gastro/goz021
Kaegi-Braun N, Schuetz P, Mueller B, Kutz A. Association of nutritional support with clinical outcomes in malnourished cancer patients: a population-based matched cohort study. Front. Nutr. 7:603370. https://doi.org/10.3389/fnut.2020.603370.
Pimentel GD, Pichard C, Laviano A, Fernandes RC (2021) High protein diet improves the overall survival in older adults with advanced gastrointestinal cancer. Clin Nutr 40(3):1376–1380. https://doi.org/10.1016/j.clnu.2020.08.028. Epub 2020 Sep 1. Erratum in: Clin Nutr. 2021 Mar 6;40(4):1441
Anderson AL, Harris TB, Tylavsky FA et al (2011) Dietary patterns and survival of older adults. J Am Diet Assoc 111:84–91
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Bozzetti, F. Does nutrition support during chemotherapy increase long-term survival of cancer patients? Lessons from the past and future perspectives. Support Care Cancer 29, 7269–7277 (2021). https://doi.org/10.1007/s00520-021-06213-w
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DOI: https://doi.org/10.1007/s00520-021-06213-w