Search

In Europe and the United States, the Foundation Aide et Recherche en Cancérologie Digestive(ARCAD)database project was initiated in 2006 and 43,488 patient data(IPD)for metastatic colorectal cancer from 59 trials have been collected and constructed as the integrated database. The ARCAD-Asia was launched in 2021 and has been actively collecting Asian clinical trials and converted IPD are stored into the integrated database. In addition, the ARCAD-Asian data are transferred to ARCAD and IPD are integrated to ARCAD global database. All the data are shared with 3 data centers of ARCAD-Asia and ARCAD, located in France, the United States and Japan. In the ARCAD database, there are 1,673 IPD treated with placebo in a salvage line setting. We are now planning to utilize placebo IPD as the synthetic control arms(SCAs)to compare the efficacies of active agents. Furthermore, we will continue to collect the Asian IPD and will expand the cancer type, leading to more comprehensive global database.

Steroid is a key drug in cancer chemotherapy-induced emesis. However, it may sometimes cause inadequately controlled hyperglycemia. Ipragliflozin is a novel selective sodium-dependent glucose cotransporter 2 inhibitor of urinary glucose excretion. In this case, we controlled steroid-induced hyperglycemia by administering ipragliflozin. The case was a 47-year-old man who was diagnosed with Stage IV esophageal cancer (T3N2M1). He had type 2 diabetes. He was treated with cisplatin (70 mg/m2; day 1) and 5-FU (700 mg/m2; days 1-4) as radiochemotherapy. Intravenous infusion of dexamethasone (9.9 mg) was administered on day 1, followed by additional doses (6.6 mg) for 3 days, as one of the emetic therapies. He received intensive insulin therapy during the first course of chemotherapy, but had Grade 3 hyperglycemia regardless. For the next treatment course, we additionally administered ipragliflozin along with dexamethasone. As a result, the hyperglycemia subsided to Grade 2. These findings suggest that ipragliflozin suppresses steroid-induced hyperglycemia.

The clinical significance of KRAS gene testing prior to using anti-epidermal growth factor receptor(EGFR)antibodies for colorectal cancer patients has been established in past randomized clinical trials. Thus, testing for the 7 most common mutations of KRAS codons 12 and 13 is now recommended as a clinical practice. However, pooled analysis of randomized controlled studies in Western countries in patients treated with cetuximab has suggested that patients with tumors showing the KRAS p. G13D mutation[a glycine(G)to aspartate(D)transition mutation] have longer overall survival and progression-free survival when compared to patients with other KRAS mutations. Furthermore, even among patients whose tumors are wild-type for KRAS codons 12 and 13, response rates are only 13~17% for anti-EGFR antibody monotherapy. These facts suggest that additional activating mutations in the RAS-RAF-MAPK or PI3K-AKT-mTOR pathways may also confer resistance to anti-EGFR antibody therapies. Indeed, recent retrospective studies have shown that mutations in KRAS codon 61 and 146, BRAF, NRAS, and PIK3CA may also predict resistance to anti-EGFR antibodies in colorectal cancer patients. On the other hand, the continuous use of anti-EGFR therapies for KRAS wild-type patients may lead to secondary resistance. Acquired EGFR or KRAS mutations have occasionally been detected among specimens from these patients. We review the latest personalized therapy available for colorectal cancer patients using KRAS mutational testing. We also illustrate future perspectives for patient selection using KRAS, BRAF, NRAS, PIK3CA, and other mutations.

Cetuximab, an anti-EGFR human/mouse chimeric antibody, has just been approved in Japan for patients with EGFR positive unresectable or recurrent colorectal cancer, as monotherapy or in combination with irinotecan. We reported two cases of unresectable or recurrent colorectal cancer effectively treated by cetuximab after the progression of the prior chemotherapy. Case 1: A51-year-old male suffered from sigmoid colon cancer with synchronous liver metastases. He received cetuximab plus irinotecan combination therapy in the third-line setting. Amonth after the initiation of the chemotherapy, abdominal CT showed tumor shrinkage of liver metastases. Case 2: A57-year-old female suffered from sigmoid colon cancer with metachronous liver, ovarian metastases, ascites and pleural effusion. Her performance status(PS)according to ECOG performance scale was 1, and she complained of dyspnea on exertion. She received cetuximab monotherapy in the fourth-line setting. Five weeks after initiation of chemotherapy, her chest, abdominal and pelvic CT showed tumor shrinkage of the liver metastases and the reduction of both ascites and pleural effusion, together with resolution of her dyspnea on exertion. Before cetuximab administration, we investigated KRAS status on cancer tissue previously resected in the above 2 cases, which showed KRAS wild-type. Cetuximab could be effective for KRAS wild-type colorectal cancer, as well as the previous reports from Western countries.