Predictive model of chemotherapy-related toxicity in elderly Chinese cancer patients

Purpose: Older cancer patients are more likely to develop and die from chemotherapy-related toxicity. However, evidence on drug safety and optimal effective doses is relatively limited in this group. The aim of this study was to develop a tool to identify elderly patients vulnerable to chemotherapy toxicity. Patients and methods: Elderly cancer patients ≥60 years old who visited the oncology department of Peking Union Medical College Hospital between 2008 and 2012 were included. Each round of chemotherapy was regarded as a separate case. Clinical factors included age, gender, physical status, chemotherapy regimen and laboratory tests results were recorded. Severe (grade ≥3) chemotherapy-related toxicity of each case was captured according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Univariate analysis was performed by chi-square statistics to determine which factors were significantly associated with severe chemotherapy toxicity. Logistic regression was used to build the predictive model. The prediction model was validated by calculating the area under the curve of receiver operating characteristic (ROC). Results: A total of 253 patients and 1,770 cases were included. The average age of the patients was 68.9 years. The incidence of grade 3–5 adverse events was 24.17%. Cancer type (non-GI cancers), BMI<20 kg/m2, KPS<90%, severe comorbidity, polychemotherapy, standard dose chemotherapy, low white blood cells count, anemia, low platelet cells count, low creatine level and hypoalbuminemia were associated with severe chemotherapy-related toxicity. We used these factors to construct a chemotherapy toxicity prediction model and the area under the ROC curve was 0.723 (95% CI, 0.687–0.759). Risk of toxicity increased with higher risk score (11.98% low, 31.51% medium, 70.83% high risk; p < 0.001). Conclusion: We constructed a predictive model of chemotherapy toxicity in elderly cancer patients based on a Chinese population. The model can be used to guide clinicians to identify vulnerable population and adjust treatment regimens accordingly.

[1]  R. de Bree,et al.  The association between skeletal muscle measures and chemotherapy‐induced toxicity in non‐small cell lung cancer patients , 2022, Journal of cachexia, sarcopenia and muscle.

[2]  Wei-Ming Huang,et al.  Pulmonary vascular volume is associated with DLCO and fibrotic score in idiopathic pulmonary fibrosis: an observational study , 2021, BMC Medical Imaging.

[3]  Sudeep Gupta,et al.  Cancer Aging Research Group (CARG) score in older adults undergoing curative intent chemotherapy: a prospective cohort study , 2021, BMJ Open.

[4]  A. Pan,et al.  Epidemiology and determinants of obesity in China. , 2021, The lancet. Diabetes & endocrinology.

[5]  H. Grabsch,et al.  Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer , 2021, JAMA oncology.

[6]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[7]  K. Shiu,et al.  Challenges in the treatment of gastric cancer in the older patient. , 2020, Cancer treatment reviews.

[8]  C. Gross,et al.  Associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors , 2020, Cancer.

[9]  Jun Zhang,et al.  Prospective comparison of the value of CRASH and CARG toxicity scores in predicting chemotherapy toxicity in geriatric oncology , 2019, Oncology letters.

[10]  F. Lordick,et al.  The performance of three oncogeriatric screening tools - G8, optimised G8 and CARG - in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study. , 2019, Journal of geriatric oncology.

[11]  N. Kassebaum,et al.  Measuring population ageing: an analysis of the Global Burden of Disease Study 2017 , 2019, The Lancet. Public health.

[12]  M. Reni,et al.  Chemotherapy in elderly patients with pancreatic cancer: Efficacy, feasibility and future perspectives. , 2019, Cancer treatment reviews.

[13]  J. Feliu,et al.  Can we avoid the toxicity of chemotherapy in elderly cancer patients? , 2018, Critical reviews in oncology/hematology.

[14]  Myung Ah Lee,et al.  Predicting cumulative incidence of adverse events in older patients with cancer undergoing first-line palliative chemotherapy: Korean Cancer Study Group (KCSG) multicentre prospective study , 2018, British Journal of Cancer.

[15]  P. Valent,et al.  Anemia at older age: etiologies, clinical implications, and management. , 2018, Blood.

[16]  F. Bozzetti,et al.  Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy. , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  T. Hsu,et al.  Comprehensive Geriatric Assessment in the Older Adult with Cancer: A Review. , 2017, European urology focus.

[18]  C. Gross,et al.  Predictors of chemotherapy dose reduction at first cycle in patients age 65 years and older with solid tumors. , 2015, Journal of geriatric oncology.

[19]  S. Yusuf,et al.  The burden of disease in older people and implications for health policy and practice , 2015, The Lancet.

[20]  H. Cohen,et al.  Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  H. Chun,et al.  Chemotherapy for Advanced Gastric Cancer: Review and Update of Current Practices , 2013, Gut and liver.

[22]  G. Lyman,et al.  Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High‐Age Patients (CRASH) score , 2012, Cancer.

[23]  F.–C. Zhang,et al.  Capecitabine for the treatment for advanced gastric cancer: efficacy, safety and ethnicity , 2012, Journal of clinical pharmacy and therapeutics.

[24]  J. Sabate,et al.  Nutritional Status Affects Treatment Tolerability and Survival in Metastatic Colorectal Cancer Patients: Results of an AGEO Prospective Multicenter Study , 2012, Oncology.

[25]  Joseph O. Deasy,et al.  Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Based Hybrid Patient and Physician Questionnaire for Head and Neck (HN) Radiotherapy Symptom Reporting , 2011 .

[26]  Supriya G Mohile,et al.  Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  B. Goh,et al.  Comparison of the pharmacokinetics and pharmacodynamics of S‐1 between Caucasian and East Asian patients , 2011, Cancer science.

[28]  W. Cheung,et al.  Impact of comorbidity on chemotherapy use and outcomes in solid tumors: a systematic review. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  O. Arrieta,et al.  Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study , 2010, BMC Cancer.

[30]  A. Brunello,et al.  Dose adjustment and supportive care before and during treatment. , 2009, Cancer treatment reviews.

[31]  E. Van Cutsem,et al.  Potential regional differences for the tolerability profiles of fluoropyrimidines. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  Lesley Seymour,et al.  Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  O. Gajic,et al.  Low baseline serum creatinine concentration predicts mortality in critically ill patients independent of body mass index* , 2007, Critical care medicine.

[34]  D. Berry,et al.  Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  T. Hickish,et al.  Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: A pooled analysis of three clinical trials. , 2006, European journal of cancer.

[36]  J. Ajani,et al.  Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  S. Wade,et al.  Prevalence and outcomes of anemia in cancer: a systematic review of the literature. , 2004, The American journal of medicine.

[38]  R. Fortinsky,et al.  Development and validation of a prognostic index for 1-year mortality in older adults after hospitalization. , 2000, JAMA.

[39]  M. Highley,et al.  Role of red blood cells in pharmacokinetics of chemotherapeutic agents. , 1999, Anti-cancer drugs.

[40]  J. Concato,et al.  The Risk of Determining Risk with Multivariable Models , 1993, Annals of Internal Medicine.

[41]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.

[42]  W. Youden,et al.  Index for rating diagnostic tests , 1950, Cancer.