FOLFIRINOX for Recurrent Pancreatic Cancer After Pancreatic Resection: A Secondary Analysis of the Nationwide Multicenter Observational Study Conducted by the Japan Adjuvant Study Group of Pancreatic Cancer 06.

OBJECTIVES: The multidrug regimen with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is widely used for recurrent pancreatic cancer after pancreatic resection. However, there are concerns about severe toxicities and poor tolerability of FOLFIRINOX in these patients because some suffer from surgery-associated malnutrition, weight loss, and diabetes mellitus. We evaluated the toxicity and tolerability of FOLFIRINOX in these patients. METHODS: This study was conducted as a secondary analysis of the Japan Adjuvant Study Group of Pancreatic Cancer 06 study, which was a multicenter observational study of FOLFIRINOX for pancreatic cancer in Japan. The toxicity and tolerability of FOLFIRINOX in recurrent disease correlated with those of both the locally advanced and the metastatic disease group. RESULTS: The major grades 3 and 4 toxicities observed in the recurrent and locally advanced or metastatic disease groups were neutropenia (68% vs 63%), febrile neutropenia (4% vs 15%, P = 0.007), thrombocytopenia (4% vs 3%), diarrhea (4% vs 8%), and sensory neuropathy (0% vs 2%). The dose modification and relative dose intensity did not differ markedly between the groups. CONCLUSIONS: The toxicity and tolerability of FOLFIRINOX for recurrence after pancreatic resection were similar to those for locally advanced or metastatic disease with appropriate patient selection and dose modifications.

Clinical Significance of Glioma-associated Oncogene 1 Expression in Patients With Locally Advanced Gastric Cancer Administered Adjuvant Chemotherapy With S-1 After Curative Surgery.

BACKGROUND/AIM: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. RESULTS: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. CONCLUSION: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease.

BACKGROUND: The guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies. METHODS: 144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed. RESULTS: Patients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as stageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In stageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology. CONCLUSIONS: Our study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with stageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis.

Long-term survival after multimodal therapy in a patient demonstrating intrahepatic cholangiocarcinoma with hilar invasion and intrahepatic metastases.

Cholangiocarcinoma is a therapeutically challenging malignancy. This report describes a case where the patient received multimodal therapy, including surgery, adjuvant chemoradiation therapy, and combination chemotherapy and successfully achieved long-term survival. Specifically, the patient achieved an extended complete response after combination chemotherapy with TS-1 (an orally administered drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine [CDHP], and oteracil potassium [Oxo]) and cisplatin for recurrence. This result suggests that chemoradiation or combination chemotherapy regimens using oral 5-fluorouracil (5-FU) analogues might therefore be helpful in patients with this malignancy. However, further clinical trials are required.

[Cisplatin, 5-fluorouracil, and high-dose leucovorin for advanced esophageal cancer].

We report the effects and toxicities of intravenous administration of cisplatin, 5-FU and high-dose leucovorin for advanced esophageal cancer. Eight patients were registered and sixteen lesions were measurable. Of these sixteen lesions, thirteen were primary or synchronous metastatic lesions, and the response was 69%. Three were recurrence lesions, and the response rate for them was 0%. Including seven neoadjuvant cases, ten patients had oral mucositis, and seven patients had appetite loss. Other toxicities were diarrhea, myelosuppression, renal dysfunction, and alopecia. All were reversible after administration. It is suggested that this treatment regimen is a superior neoadjuvant chemotherapy with low toxicity.