Tissue platinum concentration and tumor response in non-small-cell lung cancer.
OBJECTIVE
Platinum resistance is a major limitation in the treatment of advanced non-small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue platinum concentrations on response and survival in NSCLC.


METHODS
We measured total platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant platinum-based chemotherapy. Tissue platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis.


RESULTS
Tissue platinum concentration correlated significantly with percent reduction in tumor size (P < .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on platinum concentration. Patients with higher platinum concentration had longer time to recurrence (P = .034), progression-free survival (P = .018), and overall survival (P = .005) in the multicovariate Cox model analysis after adjusting for number of cycles.


CONCLUSIONS
This clinical study established a relationship between tissue platinum concentration and response in NSCLC. It suggests that reduced platinum accumulation might be an important mechanism of platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular platinum concentration are warranted.
The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 463, Houston, TX 77030, USA. esy_kim@yahoo.com
Eric S
ES
Kim
J Jack
JJ
Lee
Guangan
G
He
Chi-Wan
CW
Chow
Junya
J
Fujimoto
Neda
N
Kalhor
Stephen G
SG
Swisher
Ignacio I
II
Wistuba
David J
DJ
Stewart
Zahid H
ZH
Siddik
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D010984:Platinum / Q000378:metabolism*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D010984:Platinum; D016190:Carboplatin; D002945:Cisplatin