Top

International Journal of Clinical Oncology

Published in:

01-04-2019 | Original Article

Body composition as a predictor of toxicity after treatment with eribulin for advanced soft tissue sarcoma

Authors: Hiroshi Kobayashi, Tomotake Okuma, Hiroyuki Oka, Koichi Okajima, Yuki Ishibashi, Liuzhe Zhang, Toshihide Hirai, Takahiro Ohki, Yusuke Tsuda, Masachika Ikegami, Ryoko Sawada, Yusuke Shinoda, Toru Akiyama, Hirotaka Kawano, Takahiro Goto, Sakae Tanaka

Published in: International Journal of Clinical Oncology | Issue 4/2019

Abstract

Background

Despite the clinical benefits of eribulin on overall survival of advanced soft tissue sarcoma (STS) patients, treatment-related toxicity reduces their QOL. Body composition metrics (BCMs) are associated with poor outcome and drug toxicities in several cancers. This study investigated whether BCMs could predict drug toxicity occurrence in advanced STS patients treated with eribulin.

Methods

This study included 23 advanced STS patients treated with eribulin between March 2016 and April 2018. BCMs were evaluated using a CT scan obtained within 1 month before or after treatment initiation. The relationship of BCMs and other clinical factors was evaluated and CART analysis used to develop classification models for risk groups of drug toxicity.

Results

Sixteen patients (69.6%) experienced any grade 3/4 toxicity. Eleven patients (47.8%) developed G4 hematologic toxicity, which was significantly higher in those with low skeletal muscle gauge (SMG) (P = 0.02) and low pretreatment neutrophil count (P = 0.0002). Six patients (26.1%) had grade 3/4 non-hematologic toxicity, and was higher in those with low SMG (P = 0.004), and low serum albumin level (P = 0.02). Five patients with high BMI (P = 0.03) experienced febrile neutropenia (FN) and low pretreatment neutrophil count (P = 0.02). CART analysis classified three risk groups, and area under the receiver operating characteristic curve (AUROCC) was 0.92, 0.88, 0.92 in G4 hematologic AE, G3/4 non-hematologic AE, FN, respectively.

Conclusions

SMG is a significant predictive factor of eribulin drug toxicity in advanced STS patients. Risk classification of drug toxicity through combining predictive factors, could improve the therapeutic strategy used in chemotherapy.

Clark MA, Fisher C, Judson I et al (2005) Soft-tissue sarcomas in adults. N Engl J Med 353:701–711CrossRef

Mastrangelo G, Coindre JM, Ducimetière F et al (2012) Incidence of soft tissue sarcoma and beyond: a population-based prospective study in 3 European regions. Cancer 118:5339–5348CrossRefPubMed

Stiller CA, Trama A, Serraino D et al (2013) Descriptive epidemiology of sarcomas in Europe: report from the RARECARE project. Eur J Cancer 49:684–695CrossRef

Byerly S, Chopra S, Nassif NA et al (2016) The role of margins in extremity soft tissue sarcoma. J Surg Oncol 113:333–338CrossRefPubMed

Callegaro D, Miceli R, Bonvalot S et al (2016) Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol 17:671–680CrossRefPubMed

van der Graaf WT, Blay JY, Chawla SP et al (2012) Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet 379:1879–1886CrossRefPubMed

Schöffski P, Chawla S, Maki RG et al (2016) Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet 387:1629–1637CrossRefPubMed

Kawai A, Araki N, Sugiura H et al (2015) Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol 16:406–416CrossRefPubMed

Demetri GD, Chawla SP, von Mehren M et al (2009) Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol 27:4188–4196CrossRefPubMed

10.

Smith JA, Wilson L, Azarenko O et al (2010) Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry 49:1331–1337CrossRefPubMedPubMedCentral

11.

Towle MJ, Salvato KA, Wels BF et al (2011) Eribulin induces irreversible mitotic blockade: implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions. Cancer Res 71:496–505CrossRefPubMed

12.

Dybdal-Hargreaves NF, Risinger AL, Mooberry SL (2015) Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent. Clin Cancer Res 21:2445–2452CrossRefPubMedPubMedCentral

13.

Funahashi Y, Okamoto K, Adachi Y et al (2014) Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. Cancer Sci 105:1334–1342CrossRefPubMedPubMedCentral

14.

Yoshida T, Ozawa Y, Kimura T et al (2014) Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states. Br J Cancer 110:1497–1505CrossRefPubMedPubMedCentral

15.

Schöffski P, Ray-Coquard IL, Cioffi A et al (2011) Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. Lancet Oncol 12:1045–1052CrossRefPubMed

16.

Schöffski P, Chawla S, Maki R et al (2016) Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet 387:1629–1637CrossRefPubMed

17.

Kawai A, Araki N, Naito Y et al (2017) Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma. Jpn J Clin Oncol 47(2):137–144CrossRefPubMed

18.

Baracos VE, Arribas L (2018) Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol 1;29

19.

Prado CM, Lieffers JR, McCargar LJ et al (2008) Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9(7):629–635CrossRefPubMed

20.

Tan BH, Brammer K, Randhawa N et al (2015) Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol 41(3):333–338CrossRef

21.

Antoun S, Baracos VE, Birdsell L et al (2010) Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol 21(8):1594–1598CrossRefPubMed

22.

Daly LE, Power DG, O’Reilly Á et al (2017) The impact of body composition parameters on ipilimumab toxicity and survival in patients with metastatic melanoma. Br J Cancer 116(3):310–317CrossRefPubMedPubMedCentral

23.

Shachar SS, Deal AM, Weinberg M et al (2017) Body composition as a predictor of toxicity in patients receiving anthracycline and taxane-based chemotherapy for early-stage breast cancer. Clin Cancer Res 23(14):3537–3543CrossRefPubMedPubMedCentral

24.

Kazemi-Bajestani SM, Mazurak VC, Baracos V (2016) Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes. Semin Cell Dev Biol 54:2–10CrossRefPubMed

25.

Prado CM, Baracos VE, McCargar LJ et al (2009) Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 15:2920–2926CrossRefPubMed

26.

Weinberg M, Shachar S, Deal A et al (2016) Characterization of skeletal muscle and body mass indices in younger and older women with stage II and III breast cancer. J Am Geriatr Soc supplement:S86

27.

Kwon WA, Oh TH, Lee JW et al (2014) Predictive factors for neutropenia after docetaxel-based systemic chemotherapy in Korean patients with castration- resistant prostate cancer. Asian Pac J Cancer Prev 15(8):3443–3446CrossRefPubMed

28.

Kwon WA, Oh TH, Lee JW et al (2018) Factors that predict neutropenia in Korean patients with advanced urothelial cancer after cisplatin-based systemic chemotherapy. Urol J 15(4):168–172PubMed

29.

Razzaghdoust A, Mofid B, Moghadam M (2018) Development of a simplified multivariable model to predict neutropenic complications in cancer patients undergoing chemotherapy. Support Care Cancer. https://doi.org/10.1007/s00520-018-4224-z. (Epub ahead of print)CrossRefPubMed

30.

Nishikawa M, Miyake H, Fujisawa M (2017) Identification of risk factors predicting febrile neutropenia in patients with metastatic germ cell tumors receiving cisplatin-based combination chemotherapy. Int J Urol 24(6):449–453CrossRefPubMed

31.

Lyman GH, Dale DC, Friedberg J et al (2004) Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: a nationwide study. J Clin Oncol 22:4302–4311CrossRefPubMed

32.

Cullen MH, Billingham LJ, Gaunt CH et al (2007) Rational selection of patients for antibacterial prophylaxis after chemotherapy. J Clin Oncol 25:4821–4828CrossRefPubMed

33.

Grabowski JP, Richter R, Rittmeister H et al (2018) Impact of body mass index (BMI) on chemotherapy-associated toxicity in ovarian cancer patients. A pooled analysis of the north-eastern german society of gynecological oncology (NOGGO) databank on 1213 patients. Nticancer Res 38(10):5853–5858CrossRef

34.

Vincenzi B, Badalamenti G, Armento G et al (2018) Body mass index as a risk factor for toxicities in patients with advanced soft-tissue sarcoma treated with trabectedin. Oncology 95(1):1–7CrossRefPubMed

35.

Kosaka T, Shinojima T, Morita S et al (2018) Prognostic significance of grade 3/4 neutropenia in Japanese prostate cancer patients treated with cabazitaxel. Cancer Sci 109(5):1570–1575CrossRefPubMedPubMedCentral

36.

Di Maio M, Gridelli C, Gallo C et al (2005) Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials. Lancet Oncol 6:669–677CrossRefPubMed

37.

Shitara K, Matsuo K, Takahari D et al (2009) Neutropaenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX. Eur J Cancer 45:1757–1763CrossRefPubMed

Title: Body composition as a predictor of toxicity after treatment with eribulin for advanced soft tissue sarcoma
Authors: Hiroshi Kobayashi
Tomotake Okuma
Hiroyuki Oka
Koichi Okajima
Yuki Ishibashi
Liuzhe Zhang
Toshihide Hirai
Takahiro Ohki
Yusuke Tsuda
Masachika Ikegami
Ryoko Sawada
Yusuke Shinoda
Toru Akiyama
Hirotaka Kawano
Takahiro Goto
Sakae Tanaka
Publication date: 01-04-2019
Publisher: Springer Singapore
Published in: International Journal of Clinical Oncology / Issue 4/2019
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-018-1370-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2019

Verification of the diagnostic strategy for anterior mediastinal tumors

Histologic transformation of non-small-cell lung cancer in brain metastases

Survivin rs9904341 polymorphism significantly increased the risk of cancer: evidence from an updated meta-analysis of case–control studies

Neoadjuvant CAPOX and bevacizumab alone for locally advanced rectal cancer: long-term results from the N-SOG 03 trial

To what extent does the EQ-5D-3L correlate with the FACT-H&N of patients with oral cancer during the perioperative period?

Prognostic factors in patients who received end-of-life chemotherapy for advanced cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer