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621 Title: Effects of Proton Pump Inhibitors (PPIs) on FOLFOX and XELOX Regimens in Colorectal Cancer (CRC) Background: First-line adjuvant chemotherapy options for stage II-III CRC include XELOX (capecitabine (cape), oxaliplatin) and FOLFOX (oxaliplatin, leucovorin, 5FU). Cape is an oral 5FU prodrug, and recent studies suggested that PPIs may detrimentally affect cape efficacy. Conversely, some literature posits that PPIs may negatively impact CRC itself. Our primary objective was to compare 3-year recurrence-free survival (RFS) rates between XELOX-treated PPI-users and non-PPI users, and FOLFOX-treated PPI users and non-PPI users. Our main secondary objective was to compare overall survival (OS). Methods: We conducted a retrospective chart review of 389 stage II-III CRC patients (pts) who received adjuvant XELOX or FOLFOX from a tertiary cancer center in Alberta, Canada between 2004-2013. Information regarding PPI use, cancer treatment, and pt outcomes were gathered and analyzed from pharmacy databases. Results: 23.4% of XELOX-treated pts and 28.0% of FOLFOX -treated pts used PPIs concurrently with treatment. 3-year RFS was significantly lower in XELOX-treated PPI pts than non-PPI pts (69.5 vs. 82.6%, P=0.029). Unadjusted analysis showed that XELOX-treated PPI pts were twice as likely to experience cancer recurrence or death as XELOX-treated non-PPI pts (HR 2.03, P=0.033). FOLFOX-treated PPI pts had a non-significant increase in three-year RFS versus non-PPI pts (82.9 vs. 61.7%, P=0.066), and no significant difference in recurrence or death (HR 0.51, P=0.071). No significant differences were seen in OS. Conclusions: Our results suggest that PPIs negatively impacted RFS in early-stage XELOX-treated CRC pts, and yielded no significant effect amongst FOLFOX-treated patients. Further studies are required to corroborate our findings. [Table: see text]

e17688 Background: Cape is used to treat CRC and other cancers. Many pts take PPIs for symptom control. TRIO-013, a study of cape/oxaliplatin +/- lapatinib in metastatic gastro-esophageal cancer, f...

TPS8604 Background: Immunotherapy is a promising treatment modality for low grade non-Hodgkin’s lymphomas. SD-101 (Dynavax Technologies) is an immunostimulatory synthetic CpG molecule that activate...

Aim: Cape is used to treat GI and other malignancies. Oral drug absorption often relies on pH-dependent solubility. Many GEC patients (pts) take PPIs for symptom control, which increases gastric pH and PPIs have been shown to impact other anti-cancer drug activity. TRIO-013 is a phase III randomized trial of cape + oxaliplatin (CapeOx) with lapatinib or placebo in HER2-positive metastatic GEC. Outcomes in both arms were comparable with modern GEC studies, but adding lapatinib did not improve progression free (PFS) or overall survival (OS). This ad hoc study analysed PPI effects in both arms. Methods: Study data were reviewed. PPI use was documented by medication records. Given reported improvement on survival in younger ( Results: 545 pts were randomized 1:1 between CapeOx + lapatinib or placebo. 229 pts received PPIs (42.0%), split evenly between arms. High cape dose intensity was maintained in both arms and yet CapeOX toxicity was lower than expected. In placebo arm, PPI pts had poorer median PFS, 4.2 vs. 5.7 mo (hazard ratio [HR] 1.55, 95% CI 1.29-1.81, p = 0.0008); and OS, 9.2 vs. 11.3 mo (HR 1.34, 95% CI 1.04-1.64, p = 0.04) vs. no-PPI pts. In multivariate analysis considering age, race, stage, and gender, PPI-pts had poorer PFS (HR 1.64, 95% CI 1.38-1.90, p = 0.0002) and OS (HR 1.39, 95% CI 1.09-1.69, p = 0.03). In the lapatinib arm, PPIs had less effect on PFS (HR 1.08, p = 0.54) and OS (HR 1.26, p = 0.10). However in multivariate analysis, there was a significant difference in OS (HR 1.36, 95% CI 1.06-1.66, p = 0.03). Conclusions: PPIs negatively impacted cape efficacy possibly by raising gastric pH leading to altered cape solubility and absorption. These results are consistent with erlotinib and sunitinib studies. Whether PPIs affected lapatinib is unclear given concurrent cape use. Given cape's prevalence in breast and colon cancer, further studies are underway. Disclosure: Y.J. Huang and S. Khan-Wasti: is an employee of GSK. All other authors have declared no conflicts of interest.

2594 Background: Oral tyrosine kinase inhibitors (TKIs) are used across tumor subtypes. Oral drug absorption is dependent on numerous factors including gastric acidity. Few studies have examined ef...

e13503 Background: Renal function affects chemotherapy pharmacokinetics. Carboplatin dosing by Calvert’s formula is more pharmacologically rational, but requires an accurate glomerular filtration rate (GFR). Calvert argues that this requires measuring GFR (mGFR) instead of an estimated GFR (eGFR). Considering skeletal muscle is the major source for creatinine, this study looks to develop a new eGFR equation in cancer patients using lean body mass (LBM). Methods: We prospectively followed 22 stage IV cancer patients (10 female, 12 male; median age 69) who received carboplatin. mGFR by 24 hr creatinine clearance was compared to eGFR by Wright, Cockcroft-Gault (CG), CKD-EPI, MDRD and CT-determined LBM (eGFR = [Muscle Surface Area X 42]/CR). Simulated carboplatin dosing with each eGFR was then compared retrospectively in 100 Non-Small Cell Lung Cancer (NSCLC) patients for accuracy. Results: MDRD, CG, and Wright equations correlated variably with mGFR (R2 0.47, 0.57, and 0.69 respectively). Conversely, mGFR strongly correlated with LBM eGFR (R2 0.84). The Table compares eGFR calculations with mean residual error. In simulated carboplatin dosing of 100 stage IV NSCLC patients using LBM and CG eGFR, the mean residual error of the CG-determined carboplatin dose was 10% (0.5% min, max 39.7%, median 9.3%), assuming the LBM eGFR was better at estimating eGFR. This means that in approximately half of patients, carboplatin dose may be incorrect by CG if the new LBM eGFR method is truly more accurate. Conclusions: We propose a new formula for eGFR in cancer patients that appears superior to current formulas and may have implications for chemotherapy efficacy and toxicity. Studies to validate this formula are under way. [Table: see text]