Oxaliplatin-induced increase in splenic volume: experiences from multicenter study in Japan.

BACKGROUND: Chemotherapy with oxaliplatin is known to induce sinusoidal obstruction syndrome (SOS). In a previous single-center study, we reported that oxaliplatin-induced increase in splenic volume (SV) is strongly indicative of SOS, and that this increase in SV persisted for > 1 year after completing chemotherapy. The aim of this study was to confirm the oxaliplatin-induced SV change in a multicenter study in patients with stage III colon cancer in Japan. METHODS: We enrolled 59 patients who underwent curative resection for stage III colon cancer in the FACOS study in a phase II multi-center clinical study. Participants received mFOLFOX6 or CAPOX as adjuvant chemotherapy. SV change was assessed three times by computed tomographic volumetry: before surgery, on completion of adjuvant chemotherapy, and 1 year after completing adjuvant chemotherapy. RESULTS: SV on completing and 1 year after chemotherapy was significantly higher than that before surgery (P < 0.001). Oxaliplatin-induced SOS persisted for > 1 year after the completion of adjuvant chemotherapy in half of the patients. There was no difference in 3-year disease-free survival with respect to the presence or absence of increased SV. An increase in SV was observed in 72% of patients treated with mFOLFOX6 and 94% of patients treated with CAPOX (P = 0.13). CONCLUSION: This study can be verified the findings observed in our previous single-center study, oxaliplatin-based adjuvant chemotherapy was associated with an increase in SV. Furthermore, this increase can persist for > 1 year. The continuous presence of SOS may have a negative impact on prognosis in patients that develop recurrent disease.

Feasibility of Neoadjuvant FOLFOX Therapy Without Radiotherapy for Baseline Resectable Rectal Cancer.

BACKGROUND/AIM: The combination of oxaliplatin, leucovorin and fluorouracil (FOLFOX) has been established as postoperative adjuvant chemotherapy for stage III colon cancer. However, the safety and efficacy of neoadjuvant FOLFOX in patients with rectal cancer are still controversial. This prospective pilot study aimed to evaluate the feasibility of neoadjuvant FOLFOX therapy without radiation for baseline resectable rectal cancer (RC). PATIENTS AND METHODS: The study included 30 patients with clinical stage II/III RC between February 2012 and December 2015. The patients were treated with six cycles of FOLFOX followed by elective surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were the scheduled treatment completion rate, adverse events, pathological response and the disease-free survival (DFS) rate. RESULTS: All the patients underwent elective R0 resection after neoadjuvant FOLFOX therapy. The completion rate of the 6-cycle regimen was 93.3% (28/30 patients). Grade 3-4 adverse events occurred in seven patients (23.3%). Pathological complete response was noted in two patients (6.7%). The 3-year DFS rate was 77.5% (95% confidence interval, 61.4%-93.7%). CONCLUSION: Neoadjuvant FOLFOX therapy without radiation is a feasible therapeutic strategy for baseline resectable RC.

Oxaliplatin-induced increase in splenic volume; irreversible change after adjuvant FOLFOX.

BACKGROUND AND OBJECTIVES: Oxaliplatin can cause hepatic sinusoidal obstruction syndrome (SOS). SOS can cause chemotherapy-related adverse effects or morbidity after liver resection. Conventionally, SOS is diagnosed using liver biopsy. Recently, it was reported that increased splenic volume (SV) can be used to detect SOS. In this study, we evaluated the changes in SV during adjuvant chemotherapy. METHODS: We enrolled 103 consecutive patients with stage III and high-risk stage II colorectal cancer treated with mFOLFOX6 (n = 37) or oral fluorouracil and leucovorin (n = 66) after curative surgery. SV was measured three times; pre-operatively, after chemotherapy, and 1 year after chemotherapy. RESULTS: SV was higher after mFOLFOX6 (median 135.89 mL) than pre-operatively (105.75 mL) (P < 0.001); SV at 1-year after finishing mFOLFOX6 (114.16 mL) returned to the same level as before surgery (P = 0.0015). SV increased in 28 patients (75.7%) treated with mFOLFOX6 (95%CI, 61.8-89.5), but had not recovered in 12 of these cases (42.9%) 1 year after finishing treatment (95%CI, 17.3-47.5). In contrast, oral fluorouracil and leucovorin did not change SV. CONCLUSIONS: SV increased after adjuvant mFOLFOX6, and had not recovered in almost half of cases 1-year after finishing chemotherapy. This increase may indicate continuous SOS, which can adversely affect treatment after recurrence.