Outcomes of patients ≥65 years old with advanced cancer treated on phase I trials at MD ANDERSON CANCER CENTER.
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.
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Ishwaria M
IM
Subbiah
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
Jennifer J
JJ
Wheler
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.
Kenneth R
KR
Hess
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
David S
DS
Hong
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
Aung
A
Naing
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
Siqing
S
Fu
Moores Cancer Center, University of California, San Diego, CA.
Razelle
R
Kurzrock
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
Apostolia M
AM
Tsimberidou
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000706:statistics & numerical data; D015507:Drugs, Investigational / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018579:Patient Selection; D012307:Risk Factors; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015507:Drugs, Investigational
clinical trial; elderly; geriatrics; phase I; toxicity