PURPOSEAgarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective.METHODSThirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg) via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075). Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant.RESULTSRMBs were well tolerated at both dose levels (mean 660.9 per implant). AEs were (Grade 1/2) with no treatment-related SAEs.CONCLUSIONThe data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.

The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to mCRC. A phase III clinical trial is planned.

e14517 Background: RENCA tumor cells encapsulated in two concentric agarose layers which release signals to treat advanced cancers is a novel concept that has been substantiated in in vitro and in vivo models as reported in Cancer Research 71(3), 716-735, 2011.We report results of a phase I/II study in advanced CRC pts. Methods: Previously-treated advanced CRC pts (ECOG PS 0-2) were enrolled with informed consent obtained. Pts had intraperitoneal implantation up to 4 times via laparoscopy with 8 (37/40 pts- established dose) or 16 (3/40 pts) RENCA MB/kg. Serial exams, lab profiles, and imaging were done pre- and 3 months (mo.) post-implant to assess efficacy. Endpoints of safety, tumor marker decrease, response, and overall survival (OS) were evaluated. Results: 40 pts were implanted with RENCA MB (12 pts phase I; 28 pts phase II); 17M: 23F. Mean age 58.3. 14/40 pts had >1 implant (≥2: 14 pts; ≥3: 2 pts; =4: 2 pts). Response to MB is marked by a prominent initial rise in CRP, ESR, and IL-6, indicating a systemic inflammatory response (SIR) (100% of pts) and a parallel decrease in CEA and/or CA 19-9 in approximately 70%. SIR including its accompanying fatigue and anorexia lasts days to 3 wks. Overall, there was a statistically significant difference (p=0.009) in OS between the 70% of pts showing a decrease in tumor markers by at least 20% during the first 30 days post-implant (OS; 9.7 mo., C.I. 6.5-13.5) and those who did not (OS; 4.4 mo., C.I. 1.1-7.6). On PET-CT imaging, a striking feature of response, most often seen in pts with the longest OS, is tumor necrosis. MB were well-tolerated and no Grade ≥3 adverse events were treatment-related. Conclusions: For advanced, treatment-resistant CRC pts, early response to MB implantation characterized by tumor marker decrease in association with SIR correlates with a statistically significant increase in OS. RENCA MB represent a possible new therapeutic option for late-stage CRC. Clinical trial information: NCT01053013.

e15046 Background: RMB, a cytostatic, biological system form of anti cancer therapy have been used in Ph I & II clinical trials in mCRC w/ evidence of improved survival benefit & QOL. Evaluation of metastatic tumor response by standard CT RECIST criteria however has been unsatisfactory. We hypothesized that using 18F FDG PET/CT scan to evaluate tumor anatomy & metabolism could provide a more accurate picture of tumor response to RMB Methods: 48 mCRC pts (14, Ph 1; 34, Ph 2a) who failed available treatments were implanted intraperitoneally w/ RMB (8mb/kg). Physicals, biomarkers & lab evaluation were obtained at baseline & days 14-90, with PET CT imaging at baseline & day 90. PET scan was acquired 1 hour after FDG injection of 9.4 mCi. CT was used for attenuation correction. Correlation between 18F FDG PET SUVmax findings & CEA & or CA19-9 responses was assessed. Positive response was defined as ≥20% decrease post implant in CEA, CA19-9 & SUV. Only tumors w/ SUVmax ≥ 2.5 were evaluated. SUV measurements were made by 1 radiologist experienced in PET-CT scanning & SUV determination Results: 123 FDG positive mCRC lesions (39, Ph 1; 84 Ph 2a) were detected in 37 evaluable pts (14 m, 23 f; mean age 58.2; SUVmax 2.5-17.5). Of the 37 pts, 28 (76%) showed stabilization & or decreased FDG uptake (4 w/ frank necrosis) as well as stable/decreased CT tumor measurements. Pts w/ pulmonary lesions showed greater responses than those w/ hepatic lesions. 9 (24%) of 37 pts showed increased SUVs. 23 pts (62%) showed decrease in CEA & or CA 19-9 ≥ 20%. 17 pts (74%; 13 decrease, 4 central & peripheral necrosis) had correlation between decreased SUVs/necrosis & biomarkers decrease Conclusions: We conclude SUVs are useful in monitoring mCRC lesions response to RMB therapy. Changes in SUVs correlate w/ CEA & CA 19-9 changes. Taken together the combined data indicate anti tumor effect in these Ph 1/2a trials & offer preliminary support for our hypothesis that 18FDG can be useful in evaluating cell system therapies. Issues of SUVmax standardization & effects of intra tumor heterogeneity however must be considered. Further studies are merited & ongoing, including a planned Ph 3 trial Clinical trial information: NCT01053013; NCT00283075.

associated with shorter ePFS (p ¼ 0.029). In the subgroup of patients who did not undergo metastases' resection in their disease history (N ¼ 61), ECOG PS 0 (p ¼ 0.024), longest diameter of liver lesions < 30 mm (p ¼ 0.011) and left-sidedness (p ¼ 0.081) were independently associated with longer ePFS. Conclusion: In this contemporary cohort, the vast majority of mCRC patients with initially unresectable liver-limited disease underwent surgical procedures (73%) and further locoregional interventions (40%) in their disease history. ECOG PS, number and diameter of liver metastases, and sidedness independently predict ePFS. These factors could help physicians in personalizing the intensity and aggressiveness of liver directed treatments in mCRC patients with initially unresectable liver-limited disease.PD À 018 Comparing survival in left-sided and right-sided colorectal carcinoma: A Belgian population-based study