Expanding Beyond Maximum Grade: Chemotherapy Toxicity over Time by Age and Performance Status in Advanced Non-Small Cell Lung Cancer in CALGB 9730 (Alliance A151729)

The oncologist

article

Melisa L. Wong¹  Christine Miaskowski³  Harvey J. Cohen⁴  William A. Wood⁵  Josephine L. Feliciano⁶  Thomas E. Stinchcombe⁷  Xiaofei Wang⁸  Junheng Gao⁸  Gita Thanarajasingam⁹  Jeff A. Sloan^1,10  Amylou C. Dueck^1,10  Paul J. Novotny¹  Aminah Jatoi^1,11  Arti Hurria^1,12  Louise C. Walter² 

[1] Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California;Division of Geriatrics, University of California, San Francisco and San Francisco Veterans Affairs Medical Center;Department of Physiological Nursing, University of California;Center for the Study of Aging and Human Development, Duke University;Lineberger Comprehensive Cancer Center, Division of Hematology/Oncology, University of North Carolina;Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Center;Duke Cancer Institute, Duke University;Alliance Statistics and Data Center, Duke University;Department of Hematology, Mayo Clinic;Alliance Statistics and Data Center, Mayo Clinic;Division of Medical Oncology, Mayo Clinic;Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center;Deceased.

关键词: Geriatric oncology;    Chemotherapy;    Lung cancer;    Fatigue;    Neuropathy;   

DOI  :  10.1002/onco.13527

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes. Materials and Methods To compare fatigue and neuropathy longitudinally by age (<65, ≥65 years) and PS (0–1, 2), we analyzed data from a large phase III trial of carboplatin and paclitaxel versus paclitaxel for advanced non-small cell lung cancer (CALGB 9730, n = 529). We performed multivariable (a) linear mixed models to estimate mean AE grade over time, (b) linear regression to estimate area under the curve (AUC), and (c) proportional hazards models to estimate the hazard ratio of developing grade ≥2 AE, as well as traditional maximum grade analyses. Results Older patients had on average a 0.17-point (95% confidence interval [CI], 0.00–0.34; p = .049) higher mean fatigue grade longitudinally compared with younger patients. PS 2 was associated with earlier development of grade ≥2 fatigue (hazard ratio [HR], 1.56; 95% CI, 1.07–2.27; p = .02). For neuropathy, older age was associated with earlier development of grade ≥2 neuropathy (HR, 1.41; 95% CI, 1.00–1.97; p = .049). Patients with PS 2 had a 1.30 point lower neuropathy AUC (95% CI, −2.36 to −0.25; p = .02) compared with PS 0–1. In contrast, maximum grade analyses only detected a higher percentage of older adults with grade ≥3 fatigue and neuropathy at some point during treatment. Conclusion Our comparison of complementary but distinct aspects of chemotherapy toxicity identified important longitudinal differences in fatigue and neuropathy by age and PS that are missed by the traditional maximum grade approach. Clinical trial identification number : NCT00003117 (CALGB 9730) Implications for Practice The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time. This toxicity over time analysis of fatigue and neuropathy during chemotherapy for advanced non-small cell lung cancer demonstrates how to use longitudinal methods to comprehensively characterize AEs over time by age and performance status (PS). We identified important longitudinal differences in fatigue and neuropathy that are missed by the maximum grade approach. This new information about how older adults and patients with PS 2 experience these toxicities longitudinally may be used clinically to improve discussions about treatment options and what to expect to inform shared decision making and symptom management.

【 授权许可】

CC BY|CC BY-NC