Platinum Induced Fatty Acids: Are they Present in Plasma of Cancer Patients?

Rationale: Preclinical studies suggest that hexadeca-4,7,10,13-tetraenoic [16:4 (n-3)] induces resistance to platinum-based therapies. One study in healthy volunteers reported increases in 16:4(n-3) after consuming fish oil with levels returning to normal after 12 hours. No study has measured in 16:4(n-3) levels in non-small cell lung cancer (NSCLC) patients receiving platinum based chemotherapy.
This study aimed to determine plasma levels of 16:4(n-3) in NSCLC pts undergoing platinum-based chemotherapy in those using or not using fish oil supplements.
Methods: A method to measure 16:4(n-3) in plasma of NSCLC patients was developed and validated. Patients using fish oil (capsules or oil equivalent, n=15) and on standard of care (n=5) were selected for preliminary analysis. Plasma was prospectively collected at baseline (prior to receiving chemotherapy) and after 2 cycles of platinum-based chemotherapy. The plasma range of 16:4(n-3) at baseline and subsequently following chemotherapy were compared between those taking fish oil and those on standard of care. Plasma (80 μl) fatty acids were extracted with iso-octane, derivatized and analyzed by LC-MS/MS in positive ion mode, which enabled detection of fatty acids at <1nmol/L.
Results: At baseline, before starting chemotherapy or fish oil supplementation, all patients had detectable levels of 16:4(n-3) ranging from 8 to 160 nmol/L. Fish oil users had higher absolute values of 16:4(n-3) than standard of care (mean=47 vs 23 nmol/L; p=0.03). Changes in 16:4(n-3) concentrations after platinum based therapy were highly variable with some patients increasing and others decreasing plasma 16:4(n-3).
Conclusion: These preliminary results suggest that 16:4(n-3) may be present in NSCLC patients both before and after receiving platinum-based chemotherapy. It will be important to relate concentrations of 16:4(n-3) to chemotherapy response and survival in a larger sample of cancer patients.