Phase I trial outcomes in older patients with advanced solid tumours

• Published in: British journal of cancer Vol. 114; no. 3; pp. 262 - 268
• Main Authors: Khan, K H, Yap, T A, Ring, A, Molife, L R, Bodla, S, Thomas, K, Zivi, A, Smith, A, Judson, I, Banerji, U, de Bono, J S, Kaye, S B
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.02.2016; Nature Publishing Group
• Subjects: 692/308/2779/109/1940; 692/308/409; 692/699/67/1059; 692/700/1518; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical Study; Clinical Trials, Phase I as Topic; Cohort Studies; Comorbidity; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Molecular Medicine; Neoplasm Metastasis; Neoplasms - drug therapy; Neoplasms - epidemiology; Neoplasms - pathology; Oncology; Prognosis; Retrospective Studies; Treatment Outcome; Tumor Burden; Young Adult; experimental therapy; older patients; geriatric oncology; phase 1
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.477

Background: This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients. Methods: Clinico-pathological characteristics and treatment outcomes of all patients treated consecutively from 2005 to 2009 in phase I trials at the RMH were recorded. All toxicity and clinical outcome data were compared between patients aged below and above 65 years of age. Results: One thousand and four patients were treated in 30 Phase I trials, with 315 (31%) patients aged 65 years and older. Grade 3–5 toxicities (22.8% vs 24.8% ( P =0.52)), trial discontinuation (6% vs 4%; P =0.33), and dose interruptions (8.0% vs 8.0% ( P =0.96)) were observed at similar rates in patients below and above 65 years of age, respectively. The overall response rate 5.2% vs 4.1%, progression-free survival (PFS) 1.9 vs 3.5 months and clinical benefit rate (CBR) at 6 months 15.2% vs 14.3% were comparable in both groups. To avoid bias due to the potential therapeutic benefit of abiraterone, comparisons were repeated excluding prostate cancer patients with similar results (ORR 4.6% vs 4%, PFS 1.8 vs 3.0 months, CBR at 6 months 13.5% vs 9.5%). Multivariate analysis indicated that the previously identified RMH score (including albumin and lactate dehydrogenase levels) was an accurate predictor of outcome. Conclusions: Phase I clinical trials should be considered in patients with advanced cancers regardless of age, as older patients who enter these have similar safety and efficacy outcomes as their younger counterparts. The RMH prognostic score can assist in the selection of suitable older patients.