S-1 And Oxaliplatin Research Articles

Pathological complete response of colorectal liver metastases following chemotherapy with S-1 and oxaliplatin (SOX) in combination with bevacizumab: A case report

Pathological complete response to systemic chemotherapy is associated with more favorable survival in patients with colorectal cancer liver metastases. We present a case of a 63-year-old man with multiple liver metastases from descending colon cancer. Following surgical resection of the primary tumor, the patient received systemic chemotherapy with S-1 and oxaliplatin in combination with bevacizumab. On achievement of a markedly favorable response to chemotherapy, surgical treatment of liver metastases was performed, and the liver tumors were successfully resected without any macroscopic residue. Histopathological analyses showed necrotic tissue in the complete absence of residual viable tumor cells. This is the first reported case of a patient with multiple liver metastases from descending colorectal cancer to achieve a pathological complete response following systemic chemotherapy with S-1 and oxaliplatin in combination with bevacizumab. This regimen is a systemic chemotherapy option to 'cure' liver metastasis from colorectal cancer.

A phase II study of S-1 and oxaliplatin (SOx) combination chemotherapy as a first-line therapy for patients with advanced gastric cancer

Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer. 5-fluorouracil (5-FU) and cisplatin have been widely used in a variety of combinations. We conducted a phase II study of combination chemotherapy with new agents, S-1 and oxaliplatin (SOx), in advanced gastric cancer patients in an effort to evaluate the efficacy and toxicity of this regimen. Histologically confirmed recurrent or metastatic gastric cancer were treated by the oral administration of S-1 80 mg/m(2)/day on days 1-28, and oxaliplatin 85 mg/m(2) administered as a 90-min intravenous infusion on days 1, 15, and 29. Treatment courses were repeated every 6 weeks. Patients received a maximum of four cycles. From Feb 2006 to May 2008, 41 patients were enrolled in this study. The ratio of males to females was 28 to 13. The median patient age was 61 years (range, 36-74 years), and 85.4% (35/41) of the patients had a performance status (ECOG) of 1. The median number of chemotherapy cycles administered was 3 (range, 1-4). According to the results of our Intent-to-Treat analysis, 22 patients (53.7%) achieved a partial response (95% CI, 38-70%). 15 patients (36.6%) evidenced a stable disease, and 1 patient (2.4%) progressed during the course of the treatment. 3 patients were lost to follow-up prior to evaluation. The median time to progression and overall survival time were 4.6 months (95% CI, 3.4-5.8 months) and 7.8 months (95% CI, 6.9-8.7 months) from the start of the chemotherapy, respectively. A total of 114 cycles were assessed for toxicity. The major hematologic toxicities included grade 2 anemia (41.2%), grade 1-2 neutropenia (28.1%), and grade 1 thrombocytopenia (23.7%). Only 1 cycle of neutropenic fever occurred. The non-hematological toxicities observed were grade 3 vomiting (12.2%) and grade 3 diarrhea (4.9%). No treatment-related deaths occurred in our patient population during the study period. The SOx regimen evidenced a relatively high response rate and was well tolerated as a first-line therapy for advanced gastric cancer.

Abstract B8: A phase I pharmacokinetic (PK) study of TSU-68 plus S-1 and oxaliplatin (SOX) in patients with metastatic colorectal cancer (mCRC) treated with prior chemotherapy

Abstract Background: TSU-68 is a novel oral multiple tyrosine kinase inhibitor that inhibits VEGFR-2, FGF and PDGF receptors. Since TSU-68 inhibit angiogenesis pathway which is important to tumor growth and metastasis in human colorectal cancer, we conducted a phase I study to evaluate the safety, tolerability and PK of TSU-68 plus S-1 and oxaliplatin (SOX) in patients with metastatic colorectal cancer (mCRC) treated with prior chemotherapy. Methods and Materials: ECOG PS 0 or 1 patients with mCRC were treated with TSU-68 400 mg/day (Level 1) or 800 mg/day (Level 2) on Days 1–21, S-1 70 mg/m2 on Days 1–14 with one week rest and oxaliplatin 130 mg/m2 IV on Day 1 repeated every 3 week. The dose escalation of TSU-68 was not done more than Level 2 based on the results of phase I studies of TSU-68 alone in Japan. Results: Eleven patients were enrolled in the study. Of 11 patients, 2 patients were excluded from DLT assessment because both patients withdrew the written informed consent (IC) without a DLT during cycle 1. Of 9 evaluable patients, initial 3 patients in Level 1 experienced no DLT. Of 3 patients in Level 2, two patients experienced a DLT (one patient: grade 3 hiccup and grade 3 rash, another one: grade 2 neutropenia which prevented the initiation of the next cycle within 14 days). According to the protocol, additional 3 evaluable patients were enrolled in Level 1, and experienced no DLT. The MTD and RD of TSU-68 in combination with SOX was 400mg. Common adverse drug reactions (ADRs) in cycle 1 included peripheral sensory neuropathy (91%), nausea (82%), anorexia (82%), fatigue (46%), vomiting (36%) and diarrhoea (36%). No patient exhibited grade 4 ADR and treatment related death. Partial response was observed in 2 patients treated with prior chemotherapy. Median PFS was 218 days. TSU-68 plasma concentrations, Cmax and AUC0-t in Level 1 were higher than those in Level 2. There was no appreciable effect of administered TSU-68 on the PK of S-1 components (FT, CDHP and Oxo) and oxaliplatin-derived platinum. Conclusions: Administration of TSU-68 in combination with SOX is generally well tolerated. The MTD and RD of TSU-68 in this study was 400mg. A multi-institutional phase II study of TSU-68 at 400mg/day in combination with SOX is planned. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B8.