Feasibility Assessment of Modified FOLFOX-6 as adjuvant treatment after resection of liver metastases from colorectal cancer: analyses of a multicenter phase II clinical trial (Miyagi-HBPCOG Trial-001).

BACKGROUND/AIMS: This multicenter and single arm phase II clinical trial was performed to examine the safety and efficacy of modified FOLFOX6 (mFOLFOX6) as adjuvant treatment after resection of liver metastases from colorectal cancer. METHODOLOGY: Patients who had undergone R0-1 resection of liver metastases were assigned to 12 cycles of mFOLFOX6. The primary end point was disease-free survival (DFS). RESULTS: We enrolled 49 cases and analyzed adverse events in 48 cases, since in one patient cancer recurred before starting treatment. As to the relative dose intensity, 5-FU was 78.8%, and oxaliplatin was 75.9%. Adverse events of Grade 3 and above includ- ed 18 cases of neutropenia (37.5%), 4 cases of sensory neuropathy (8.3%), 4 cases of thrombocytopenia (8.3%) and 4 cases of allergy (8.3%), and there were no cases of fatality caused by adverse events. The most difference of adverse event compared with MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) was thrombocytopenia. The 2-year DFS was 59.2% (95% CI: 36.7-78.4) in the 49 enrolled cases. CONCLUSION: mFOLFOX6 after hepatectomy was tolerable. And mFOLFOX6 also seemed to improve DFS. mFOLFOX is one of the options for such patients and appears promising as an adjuvant treatment.

Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study.

PURPOSE: The present phase III study was designed to investigate the noninferiority of S-1 alone and superiority of gemcitabine plus S-1 compared with gemcitabine alone with respect to overall survival. PATIENTS AND METHODS: The participants were chemotherapy-naive patients with locally advanced or metastatic pancreatic cancer. Patients were randomly assigned to receive only gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle), only S-1 (80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle), or gemcitabine plus S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle). RESULTS: In the total of 834 enrolled patients, median overall survival was 8.8 months in the gemcitabine group, 9.7 months in the S-1 group, and 10.1 months in the gemcitabine plus S-1 group. The noninferiority of S-1 to gemcitabine was demonstrated (hazard ratio, 0.96; 97.5% CI, 0.78 to 1.18; P < .001 for noninferiority), whereas the superiority of gemcitabine plus S-1 was not (hazard ratio, 0.88; 97.5% CI, 0.71 to 1.08; P = .15). All treatments were generally well tolerated, although hematologic and GI toxicities were more severe in the gemcitabine plus S-1 group than in the gemcitabine group. CONCLUSION: Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall survival with good tolerability and presents a convenient oral alternative for locally advanced and metastatic pancreatic cancer.

[Long-term survival case after liver resection and postoperative hepatic arterial infusion for multiple liver metastases from rectal cancer].

A 45-year-old man underwent a low anterior resection for rectal cancer [T3, N1, M0, Stage IIa: UICC]. He received a postoperative systemic chemotherapy with 5-FU and LV. Five months after the operation, multiple liver metastases were detected in the right hepatic lobe (S5, 6, 8). Right hepatectomy was performed. Seventeen courses of postoperative hepatic arterial infusion (HAI) chemotherapy (weekly high-dose 5-FU regimen) were performed without severe adverse events. He was still alive with no sign of recurrence for 69 months after hepatectomy. After liver resection for metastases of colorectal cancer, although a systemic chemotherapy has been mainly performed, HAI chemotherapy is one of the important options for prevention of local recurrence.

Synergistic antitumor effect of an angiogenesis inhibitor (TNP-470) and tumor necrosis factor in mice.

PURPOSE: We investigated the potentiation of combination therapy using tumor necrosis factor (TNF) with TNP-470, a potent angiogenesis inhibitor. METHODS: We evaluated the antitumor effect in vivo against subcutaneous (s.c.) MC38 mouse colon adenocarcinoma tumors in C57BL/6 mice. The mice were treated with a single bolus injection via the tail vein of 3 or 8 microg rhTNF in 0.5% bovine serum albumin/normal saline (BSA/NS), or with 0.5% BSA/NS alone as a control, with or without TNP-470 pretreatment, given as 30 or 60 mg/kg x 2 days, s.c. DNA synthesis in human umbilical endothelial cells (HUVEC) was assessed by [(3)H]thymidine uptake after incubation with TNF, with or without TNP-470. RESULTS: The antitumor effect of TNP-470 pretreatment combined with 3 microg recombinant human (rh) TNF injection resulted in an 80% reduction of tumor volume compared with the control. This was significantly better than that induced by 3 microg rhTNF alone (P < 0.005). DNA synthesis in HUVEC was inhibited by TNF with TNP-470 in a dose-dependent manner, but there was no enhanced effect against MC38 in vitro. CONCLUSIONS: These results suggest that the combination of the angiogenesis inhibitor TNP-470 and TNF might have a synergistic antitumor effect on solid tumors in vivo.