Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER)
BackgroundAlternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer.Patients and methodsEligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival.ResultsOf 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75–88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7–9.5 months). The median overall survival was 23.1 months (95% CI 17.4–28.8 months). The response rate was 44% (95% CI 30.2–57.8%), and the disease control rate was 88% (95% CI 79.0–97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events.ConclusionS-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.
Retrospective Analysis of S-1 plus Bevacizumab as Maintenance Therapy after Induction of S-1 and Oxaliplatin (SOX) plus Bevacizumab as First-Line Chemotherapy in Patients with Metastatic Colorectal Cancer
Background: 
The SOFT study was a phase III trial designed to validate the non-inferiority of S-1 and oxaliplatin (SOX) plus 
bevacizumab to mFOLFOX6 plus bevacizumab in terms of PFS in patients 
with metastatic colorectal cancer (mCRC) who had not previously received 
chemotherapy. In this study, we retrospectively reviewed cases in which S-1 
plus bevacizumab as maintenance therapy after induction of S-1 and Oxaliplatin 
(SOX) plus bevacizumab as first-line chemotherapy in patients with metastatic 
colorectal cancer was applied in order to evaluate its efficacy and safety in 
clinical practice. Material and method: Among the 40 patients with mCRC at the 
Fuchu Hospital who received SOX plus bevacizumab 
as a first line treatment between August 2013 and December 2018. The eligible 
patients had histologically confirmed mCRC. On day 1 of each 3-week period during the study, 
patients in the SOX plus bevacizumab received a 7.5 mg/kg intravenous infusion 
of bevacizumab, followed by an intravenous infusion of 130 mg/m2 oxaliplatin. 
S-1 (40 - 60 mg) was 
administered orally two times per day from after dinner on day 1 to after breakfast on day 15, followed by a 7-day rest. Results: The median PFS was 15.0 months and median OS was 
36.0 months. The response rate (RR: complete pus partial response) was 85.0%, 
and the disease control rate (DCR: RR plus stable disease) was 92.5%. The most common adverse 
events with SOX plus bevacizumab were hypertension (50%), neurosensory toxicity 
(50%), anorexia (32.5%), fatigue (45%), 
pigmentation (39%), Neutrophil count decreased (30%), and platelet count decreased (40%). The most 
common grade 3/4 adverse events were 
neurosensory toxicity (5%) and fatigue (9%). Conclusion: This study revealed that 
the survival benefit of S-1 and oxaliplatin (SOX) plus bevacizumab in Japanese 
patients with mCRC was like that observed in previous clinical trials. 
Therefore, S-1 and oxaliplatin (SOX) plus bevacizumab can be considered as 
routine first-line treatment option for patients with mCRC.
Monte Carlo Study of the Effect of Backscatter Materail Thickness on 99 mTc Source Response in Single Photon Emission Computed Tomography
Introduction SPECT projections are contaminated by scatter radiation, resulting in reduced image contrast and quantitative errors. Backscatter constitutes a major part of the scatter contamination in lower energy windows. The current study is an evaluation of the effect of backscatter material on FWHM and image quality investigated by Monte Carlo simulation. Materials and Methods SIMIND program was used for simulation of a Siemen’s dual-head variable angle scintillation gamma camera. Planar and SPECT scanning of a 99m Tc source and a Jaszczak phantom for varying thicknesses of Perspex slabs, as a backscatter media, were analyzed using the photopeak and scatter windows. Simulated planar images and reconstructed tomographic images were evaluated qualitatively, by two nuclear medicine specialists, and quantitatively, by Structural Similarity (SSIM) Index. Results In the 99m Tc photopeak window, no significant change in total counts due to backscatter material was measured. In the scatter windows, scattering was overestimated compared with a simulated backscatter free SPECT system. For instance, at a thickness of 10 cm, total counts of a 99m Tc source detected in the 72 keV windows eventually doubled with increasing backscatter material, compared with the situation without backscatter material. The backscatter contribution plateaued when more than 7 cm of scatter material was placed but there were optimized results for a backscatter thickness of 4.5 cm. Better image quality for the thickness was confirmed by the results of eye interpretation and also by SSIM algorithm. Conclusion Backscatter should be taken into account, particularly in model-based scatter correction methods in SPECT for an accurate simulation system optimization.