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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Dynapenia could predict chemotherapy-induced dose-limiting neurotoxicity in digestive cancer patients

Authors: Damien Botsen, Marie-Amélie Ordan, Coralie Barbe, Camille Mazza, Marine Perrier, Johanna Moreau, Mathilde Brasseur, Yohann Renard, Barbara Taillière, Florian Slimano, Eric Bertin, Olivier Bouché

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

FIGHTDIGO study showed the feasibility and acceptability of handgrip strength (HGS) measure in routine in 201 consecutive patients with digestive cancer treated with ambulatory chemotherapy. The present study focuses on the second aim of FIGHTDIGO study: the relationships between pre-therapeutic dynapenia and chemotherapy-induced Dose-Limiting Toxicities (DLT).

Methods

In this ancillary prospective study, DLT were analyzed in a sub-group of 45 chemotherapy-naive patients. Two bilateral consecutive measures of HGS were performed with a Jamar dynamometer before the first cycle of chemotherapy. Dynapenia was defined as HGS < 30 kg (men) and < 20 kg (women). DLT and/or Dose-Limiting Neurotoxicity (DLN) were defined as any toxicity leading to dose reduction, treatment delays or permanent treatment discontinuation.

Results

Two-thirds of chemotherapies were potentially neurotoxic (n = 31 [68.7%]) and 22 patients (48.9%) received FOLFOX (5FU, leucovorin plus oxaliplatin) regimen chemotherapy. Eleven patients (24.4%) had pre-therapeutic dynapenia. The median number of chemotherapy cycles was 10 with a median follow-up of 167 days. Twenty-two patients experienced DLT (48.9%). There was no significant association between pre-therapeutic dynapenia and DLT (p = 0.62). Nineteen patients (42.2%) experienced DLN. In multivariate analysis, dynapenia and tumoral location (stomach, biliary tract or small intestine) were independent risk factors for DLN (HR = 3.5 [1.3; 9.8]; p = 0.02 and HR = 3.6 [1.3; 10.0]; p = 0.01, respectively).

Conclusions

Digestive cancer patients with pre-therapeutic dynapenia seemed to experience more DLN. HGS routine measurement may be a way to screen patients with frailty marker (dynapenia) who would require chemotherapy dose adjustment and adapted physical activity programs.

Trial registration

NCT02797197 June 13, 2016 retrospectively registered.
Literature
1.
2.
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.CrossRef
3.
Manini TM, Clark BC. Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci. 2012;67(1):28–40.CrossRef
4.
Evans WJ, Campbell WW. Sarcopenia and age-related changes in body composition and functional capacity. J Nutr. 1993;123(2 Suppl):465–8.CrossRef
5.
Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis. Age Ageing. 2010;39(4):412–23.CrossRef
6.
Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutr. 1989;5(5):303–11 discussion 312-13.
7.
Massicotte M-H, Borget I, Broutin S, Baracos VE, Leboulleux S, Baudin E, et al. Body composition variation and impact of low skeletal muscle mass in patients with advanced medullary thyroid carcinoma treated with vandetanib: results from a placebo-controlled study. J Clin Endocrinol Metab. 2013;98(6):2401–8.CrossRef
8.
Huillard O, Boissier E, Blanchet B, Thomas-Schoemann A, Cessot A, Boudou-Rouquette P, et al. Drug safety evaluation of sorafenib for treatment of solid tumors: consequences for the risk assessment and management of cancer patients. Expert Opin Drug Saf. 2014;13(5):663–73.CrossRef
9.
Cousin S, Hollebecque A, Koscielny S, Mir O, Varga A, Baracos VE, et al. Low skeletal muscle is associated with toxicity in patients included in phase I trials. Investig New Drugs. 2014;32(2):382–7.CrossRef
10.
Huillard O, Mir O, Peyromaure M, Tlemsani C, Giroux J, Boudou-Rouquette P, et al. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer. 2013;108(5):1034–41.CrossRef
11.
Mir O, Coriat R, Blanchet B, Durand J-P, Boudou-Rouquette P, Michels J, et al. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS One. 2012;7(5):e37563.CrossRef
12.
Daly LE, Power DG, O’Reilly Á, Donnellan P, Cushen SJ, O’Sullivan K, et al. The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma. Br J Cancer. 2017;116(3):310–7.CrossRef
13.
Prado CMM, Antoun S, Sawyer MB, Baracos VE. Two faces of drug therapy in cancer: drug-related lean tissue loss and its adverse consequences to survival and toxicity. Curr Opin Clin Nutr Metab Care. 2011;14(3):250–4.CrossRef
14.
Sawyer M, Ratain MJ. Body surface area as a determinant of pharmacokinetics and drug dosing. Investig New Drugs. 2001;19(2):171–7.CrossRef
15.
Gurney H. How to calculate the dose of chemotherapy. Br J Cancer. 2002;86(8):1297–302.CrossRef
16.
Morgan DJ, Bray KM. Lean body mass as a predictor of drug dosage. Implications for drug therapy. Clin Pharmacokinet. 1994;26(4):292–307.CrossRef
17.
Aslani A, Smith RC, Allen BJ, Pavlakis N, Levi JA. The predictive value of body protein for chemotherapy-induced toxicity. Cancer. 2000;88(4):796–803.CrossRef
18.
Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015;14(1):58–74.CrossRef
19.
Kilgour RD, Vigano A, Trutschnigg B, Hornby L, Lucar E, Bacon SL, et al. Cancer-related fatigue: the impact of skeletal muscle mass and strength in patients with advanced cancer. J Cachexia Sarcopenia Muscle. 2010;1(2):177–85.CrossRef
20.
Norman K, Stobäus N, Smoliner C, Zocher D, Scheufele R, Valentini L, et al. Determinants of hand grip strength, knee extension strength and functional status in cancer patients. Clin Nutr Edinb Scotl. 2010;29(5):586–91.CrossRef
21.
Chen C-H, Null H-C, Huang Y-Z, Hung T-T. Hand-grip strength is a simple and effective outcome predictor in esophageal cancer following esophagectomy with reconstruction: a prospective study. J Cardiothorac Surg. 2011;6:98.CrossRef
22.
Kilgour RD, Vigano A, Trutschnigg B, Lucar E, Borod M, Morais JA. Handgrip strength predicts survival and is associated with markers of clinical and functional outcomes in advanced cancer patients. Support Care Cancer. 2013;21(12):3261–70.CrossRef
23.
Ordan M-A, Mazza C, Barbe C, Perrier M, Botsen D, Renard Y, et al. Feasibility of systematic handgrip strength testing in digestive cancer patients treated with chemotherapy: the FIGHTDIGO study: feasibility of handgrip strength. Cancer. 2017; [Epub ahead of print].
24.
Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc. 2002;50(5):889–96.CrossRef
25.
Prado CMM, Lieffers JR, Bowthorpe L, Baracos VE, Mourtzakis M, McCargar LJ. Sarcopenia and physical function in overweight patients with advanced cancer. Can J Diet Pract. 2013;74(2):69–74.CrossRef
26.
27.
André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343–51.CrossRef
28.
Puts MTE, Monette J, Girre V, Pepe C, Monette M, Assouline S, et al. Are frailty markers useful for predicting treatment toxicity and mortality in older newly diagnosed cancer patients? Results from a prospective pilot study. Crit Rev Oncol Hematol. 2011;78(2):138–49.CrossRef
29.
Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRef
30.
Wagner AD, Grothe W, Behl S, Kleber G, Grothey A, Haerting J, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2005;2:CD004064.
31.
Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer. 2007;96(6):896–902.CrossRef
32.
Kishiki T, Masaki T, Matsuoka H, Kobayashi T, Suzuki Y, Abe N, et al. Modified Glasgow prognostic score in patients with incurable stage IV colorectal cancer. Am J Surg. 2013;206(2):234–40.CrossRef
33.
McMillan DC. The systemic inflammation-based Glasgow prognostic score: a decade of experience in patients with cancer. Cancer Treat Rev. 2013;39(5):534–40.CrossRef
34.
Prado CMM, Maia YLM, Ormsbee M, Sawyer MB, Baracos VE. Assessment of nutritional status in cancer--the relationship between body composition and pharmacokinetics. Anti Cancer Agents Med Chem. 2013;13(8):1197–203.CrossRef
35.
Prado CMM, Baracos VE, McCargar LJ, Mourtzakis M, Mulder KE, Reiman T, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res Off J Am Assoc Cancer Res. 2007;13(11):3264–8.CrossRef
36.
Ali R, Baracos VE, Sawyer MB, Bianchi L, Roberts S, Assenat E, et al. Lean body mass as an independent determinant of dose-limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens. Cancer Med. 2016;5(4):607–16.CrossRef
37.
Gebremedhn EG, Shortland PJ, Mahns DA. The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review. BMC Cancer. 2018;18(1):410.CrossRef
38.
Steffl M, Musalek M, Kramperova V, Petr M, Kohlikova E, Holmerova I, et al. Assessment of diagnostics tools for sarcopenia severity using the item response theory (IRT). J Nutr Health Aging. 2016;20(10):1051–5.CrossRef
39.
Baracos VE, Arribas L. Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol Off J Eur Soc Med Oncol. 2018;29(suppl_2):ii1–9.CrossRef
40.
Anandavadivelan P, Brismar TB, Nilsson M, Johar AM, Martin L. Sarcopenic obesity: a probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients. Clin Nutr Edinb Scotl. 2016;35(3):724–30.CrossRef
41.
Antoun S, Borget I, Lanoy E. Impact of sarcopenia on the prognosis and treatment toxicities in patients diagnosed with cancer. Curr Opin Support Palliat Care. 2013;7(4):383–9.CrossRef
42.
Gray M, Glenn JM, Binns A. Predicting sarcopenia from functional measures among community-dwelling older adults. Age Dordr Neth. 2016;38(1):22.CrossRef
43.
Dodds RM, Syddall HE, Cooper R, Kuh D, Cooper C, Sayer AA. Global variation in grip strength: a systematic review and meta-analysis of normative data. Age Ageing. 2016;45(2):209–16.CrossRef
44.
Sampaio RAC, Sampaio PYS, Castaño LAA, Barbieri JF, Coelho HJ, Arai H, et al. Cutoff values for appendicular skeletal muscle mass and strength in relation to fear of falling among Brazilian older adults: cross-sectional study. Sao Paulo Med J Rev Paul Med. 2017;135(5):434–43.CrossRef
Metadata
Title
Dynapenia could predict chemotherapy-induced dose-limiting neurotoxicity in digestive cancer patients
Authors
Damien Botsen
Marie-Amélie Ordan
Coralie Barbe
Camille Mazza
Marine Perrier
Johanna Moreau
Mathilde Brasseur
Yohann Renard
Barbara Taillière
Florian Slimano
Eric Bertin
Olivier Bouché
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4860-1

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