Platinum tissue concentrations predict NSCLC treatment response

Sep 13 2012

By medwireNews Reporters

Reduced tissue platinum accumulation might explain why some patients with non-small-cell lung cancer (NSCLC) fail to respond to platinum-based chemotherapy, research shows.

In an analysis of 44 archived fresh-frozen NSCLC specimens, tissue platinum concentration was significantly correlated with reductions in tumor size and survival.

Overall, high platinum concentrations were associated with a significant 64% improvement in time to recurrence, a 63% improvement in progression-free survival, and a 74% improvement in overall survival compared with patients with low platinum concentrations.

The findings, published in the Journal of Clinical Oncology, suggest that "reduced drug accumulation is a significant mechanism of platinum resistance in clinical tumor specimens," say Eric Kim (University of Texas MD Anderson Cancer Center, Houston, USA) and colleagues.

The NSCLC specimens were taken from patients who underwent surgical resection after neoadjuvant platinum-based chemotherapy. All 44 patients received a doublet consisting of cisplatin, carboplatin, or cisplatin followed by carboplatin. Three-quarters of the patients had stage IIb or IIIa disease.

Using flameless atomic absorption spectrophotometry (FAAS), the researchers report that tissue platinum concentration significantly correlated with the percent reduction in tumor size, as well as overall survival and time to recurrence.

The correlation was observed for patients treated with carboplatin, cisplatin, and in all subgroups, such as patients with adenocarcinomas and squamous cell carcinomas.

Patients with high levels of platinum concentrations, defined as above the median concentration were also a significant seven times more likely to have a partial response to therapy compared with patients with a low concentration, defined as below the median concentration (odds ratio=7.07).

First-line platinum-based chemotherapy in NSCLC has a response rate of 20% to 30% because a significant proportion of tumors have intrinsic or de novo resistance.

In their paper, Kim and colleagues say that understanding the molecular mechanisms of platinum accumulation by tumor cells is critical as it remains necessary to identify surrogate biomarkers for platinum accumulation.

In doing so, the hope is these biomarkers could be developed and used prospectively to personalize chemotherapy, they state.

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