Outcomes of patients ≥65 years old with advanced cancer treated on phase I trials at MD ANDERSON CANCER CENTER. Issue 1 (17th October 2016)

• Record Type: Journal Article
• Authors: Subbiah, Ishwaria M.; Wheler, Jennifer J.; Hess, Kenneth R.; Hong, David S.; Naing, Aung; Fu, Siqing; Kurzrock, Razelle; Tsimberidou, Apostolia M.
• Is Part Of: International journal of cancer. Volume 140:Issue 1(2017:Jan. 01)
• Page Start: 208
• Page End: 215
• Publication Date: 2016-10-17
• Subjects: elderly -- phase I -- toxicity -- geriatrics -- clinical trial; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30417
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Patients ≥65 years with cancer remain underrepresented in clinical trials, particularly in phase I clinical trials. We analyzed the clinical course of patients ≥65 years treated on phase I clinical trials with particular emphasis on toxicities. We identified 347 consecutive patients ≥65 years with advanced cancer in our phase I clinic from 01/2004‐12/2009 and analyzed disease characteristics, toxicities, survival and response. Overall, 251 patients received a targeted agent, of whom 241 (96%) received an investigational, non‐FDA‐approved drug. Clinical benefit (complete response + partial response + stable disease ≥ 6 months) was noted in 61 patients (18%). Eighty‐nine patients (26%) had grade 3/4 toxicity, commonly hematologic, including 6 dose‐limiting toxicities and 1 treatment‐related death (<0.01%). Median overall survival from first Phase I Clinic visit was 8.8 months (95% CI: 7.8–10.6); median time to treatment failure was 1.9 months (95% CI: 1.8–2.1). Multivariable analyses revealed 4 indicators of lack of clinical benefit (liver metastases, performance status [PS] >1, prior radiation, ≥5 prior treatments; p <0.0001). Patients age 70–79 years had a greater risk of grade 3/4 toxicities when treated with combinations (≥2 drugs) compared to monotherapy ( p = 0.006). Predictors of shorter time to treatment failure and overall survival included PS >1, thrombocytosis, >2 metastatic sites, and elevated lactate dehydrogenase ( p <0.05). Our results suggest that phase I clinical trials are well tolerated in patients ≥65 years. Additionally, we identified risk factors that may facilitate patient selection for clinical trial participation. Abstract : What's new? The incidence of cancer is nine times higher in persons over age 65 than it is in younger individuals. Yet, senior patients are underrepresented in clinical trials, partly out of concern for toxicities. Here, investigation of the incidence of grade 3/4 toxicities in elderly patients participating in phase I clinical trials shows that about one‐quarter of elderly patients treated with experimental therapies experienced a high grade toxicity. Those 70 or older were at increased risk of toxicity particularly when given two or more drugs. A criteria‐based score was developed to predict whether patients would benefit clinically from trial participation.