Kohei Akiyoshi

A Prospective, Multicenter Phase II Study of the Efficacy and Feasibility of 15-minute Panitumumab Infusion Plus Irinotecan for Oxaliplatin- and Irinotecan-refractory, KRAS Wild-type Metastatic Colorectal Cancer (Short Infusion of Panitumumab Trial)

Background: In some recently updated clinical guidelines, the fully humanized monoclonal antibody panitumumab, combined with irinotecan, has been recommended as an optional third‐line chemotherapy for KRAS wild‐type metastatic colorectal cancer (mCRC). The present prospective, multicenter phase II study evaluated the effectiveness and safety of short 15‐minute panitumumab infusions. Patients and Methods: From January 2011 to December 2011, patients with KRAS wild‐type mCRC were enrolled at 8 centers. The key eligibility criteria were age ≥ 20 years and resistance or intolerance to irinotecan, fluoropyrimidine, and oxaliplatin. All patients received 6 mg/kg of panitumumab and 150 mg/m2 or the previous tolerated dose of irinotecan, biweekly, until disease progression or unacceptable toxicity. The initial panitumumab infusion was 60 minutes, followed by a 30‐minute infusion and then 15‐minute infusions. The primary endpoint was the confirmed response rate using Response Evaluation Criteria In Solid Tumors, version 1.0. The secondary endpoints were progression‐free survival, overall survival, and toxicity. The trial is registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN no. 000004647). Results: Of the 43 patients, the median age was 62 years (range, 32–75 years), 58% were male, and the Eastern Cooperative Oncology Group performance status was 0 to 1. The total response rate was 37.2% (95% confidence interval [CI], 23.0–53.3), and the confirmed response rate was 18.6% (95% CI, 8.4–33.4). The median progression‐free and overall survival were 5.8 months (95% CI, 3.3–8.4 months) and 13.6 months (95% CI, 10.8–16.5 months), respectively. The most frequent grade 3/4 toxicities were anorexia (12%), leukopenia (9%), and neutropenia (9%). Nine patients did not reach the 15‐minute infusion, primarily because of disease progression. No infusion‐related reactions were observed. Conclusion: The short 15‐minute panitumumab infusion regimen was well tolerated, without compromising safety or efficacy in patients with KRAS wild‐type, oxaliplatin‐ and irinotecan‐refractory mCRC. Micro‐Abstract: The present prospective, multicenter phase II study was conducted to evaluate the feasibility of shorter, 15‐minute panitumumab infusions in patients with KRAS wild‐type oxaliplatin‐ or irinotecan‐refractory metastatic colorectal cancer. The findings indicate that 15‐minute panitumumab infusions has efficacy similar to that in previous reports, with no infusion‐related reactions or increases in the frequency or severity of adverse events.

Morphological study of the TK cholangiocarcinoma cell line with three-dimensional cell culture

Cholangiocarcinoma is an intractable carcinoma originating from the bile duct epithelium. To gain an understanding of the cell biology of cholangiocarcinoma, in vitro cell culture is valuable. However, well‑characterized cell lines are limited. In the present study, the morphology of the TK cholangiocarcinoma cell line was analyzed by three‑dimensional culture. Dispersed TK cells were injected into a gelatin mesh scaffold and cultivated for 3‑20 days. The morphology of the TK cells was investigated by phase‑contrast microscopy, optical microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). TK cells were observed to proliferate three-dimensionally in the scaffold. The cells exhibited a globoid structure and attached to the scaffold. The SEM observation demonstrated typical microvilli and plicae on the surface of the structure. Light microscopy and TEM confirmed intercellular and cell‑to‑scaffold attachment in the three‑dimensional mesh. The culture also exhibited the formation of a duct-like structure covered by structured microvilli. In conclusion, three‑dimensional culture of TK cells demonstrated the morphological characteristics of cholangiocarcinoma in vitro. Production of high levels of carbohydrate antigen (CA)19‑9, CA50 and carcinoembryonic antigen was previously confirmed in the TK cell line. As a characteristic morphology was demonstrated in the present study, the TK cholangiocarcinoma cell line may be useful as an experimental model for further study of cholangiocarcinoma.

Phase II study of cetuximab with irinotecan for KRAS wild-type colorectal cancer in Japanese patients.

Cetuximab improves the prognosis for wild‐type KRAS metastatic colorectal cancer (MCRC). We evaluated the safety and efficacy of cetuximab in combination with irinotecan in Japanese patients with wild‐type KRAS MCRC refractory to irinotecan, oxaliplatin and fluoropyrimidines.

Cholangiocarcinoma cell line TK may be useful for the pharmacokinetic study of the chemotherapeutic agent gemcitabine.

Cholangiocarcinoma is a disease with a poor prognosis. A human cholangiocarcinoma cell line, TK, was previously established to enable further understanding of the disease. We conducted this investigation to determine whether or not the TK line is useful for pharmacokinetic study of the chemotherapeutic agent gemcitabine (GEM). Along with the BXPC3 human pancreatic adenocarcinoma cell line, the sensitivity to and effects on the TK cell line of GEM were compared. The influence of deoxycytidine kinase (dCK) transduction was also comparatively investigated. The effects of GEM in terms of drug sensitivity of the TK cell line, cell cycle and levels of transcripts of key enzymes were comparable to the BXPC3 cell line. Responses to the drug were similar in both cell lines. In contrast to pancreatic carcinoma, cell lines for research on cholangiocarcinoma have been limited. This study suggests the application of the TK cell line to the pharmacokinetic study of the chemosensitization of therapeutic drugs, such as GEM.