Survival of patients in a Phase 1 Clinic: the M. D. Anderson Cancer Center experience.
BACKGROUND
Patients with advanced malignancies for whom standard therapy is ineffective may participate in phase 1 trials. To gain a better understanding of the clinical features that could influence benefit versus risk, the authors of this report assessed prognostic factors and survival for patients who were referred to a phase 1 clinic focused primarily on targeted agents.


METHODS
The medical records of 200 sequential patients who presented to the Phase 1 Clinic at The University of Texas M. D. Anderson Cancer Center were reviewed, and their characteristics and survival were analyzed.


RESULTS
The median patient age was 58 years (range, 12-85 years), and 57% of patients were men. The median number of prior therapies was 4. Of 200 patients, 182 were treated on at least 1 phase 1 clinical trial. The median follow-up of surviving patients was 21 months, and the median overall survival was 9 months (95% confidence interval [CI], 7.4-10.8). In univariate analysis, the factors that predicted shorter survival were primary tumor in the gastrointestinal tract; a history of thrombosis, liver metastases, and elevated levels of serum lactate dehydrogenase; platelet count; carbohydrate antigen 9 (Ca19-9) and Ca-125 levels; aspartate aminotransferase levels, and alkaline phosphatase levels (P < .05 for each). In multivariate analysis, independent factors that predicted shorter survival were a history of thromboembolism (hazard ratio [HR], 2.38; 95% CI, 1.29-4.39; P = .005), platelets >or=440 x 10(9)/L (HR, 1.72; 95% CI, 1.12-2.65; P = .014), and the presence of liver metastases (HR, 1.51; 95% CI, 1.09-2.09; P = .013).


CONCLUSIONS
Patients who were referred to phase 1 studies had a short median survival (9 months). Patients with thrombocytosis, liver metastases, and a history of thromboembolism had worse outcomes. A prognostic score is proposed.
Wheler
Jennifer
J
Department of Investigational Cancer Therapeutics (a Phase 1 Program), The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77230-1402, USA. jjwheler@mdanderson.com
Tsimberidou
Apostolia M
AM
Hong
David
D
Naing
Aung
A
Jackson
Tiffiny
T
Liu
Suyu
S
Feng
Lei
L
Kurzrock
Razelle
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D017321:Clinical Trials, Phase I as Topic / Q000401:mortality*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D013922:Thrombocytosis / Q000150:complications; D013923:Thromboembolism / Q000150:complications; D016896:Treatment Outcome
D000970:Antineoplastic Agents