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Background: First-line treatment with FOLFOXIRI plus bevacizumab (BEV) is highly effective and regarded as one of the standards-of-care for patients with metastatic colorectal cancer (mCRC), despite the high incidence of neutropenia and diarrhea as side effects. AXEPT, an Asian phase III study, showed that modified CAPIRI+BEV [capecitabine (CAP: 1600 mg/m 2 ), irinotecan (IRI: 200 mg/m 2 ), and BEV (7.5 mg/m 2 )] was non-inferior to FOLFIRI+BEV as a second-line therapy for mCRC patients and was associated with a lower incidence of hematologic toxicities. Thus, a reduced dose of the CAP and IRI regimen in combination with oxaliplatin (OX) and BEV (CAPOXIRI+BEV) may be more feasible than FOLFOXIRI+BEV, without compromising efficacy., Methods: QUATTRO-II is an open-label, multicenter, randomized phase II study. In Step 1, the recommended doses of OX and IRI will be investigated as a safety lead-in. In Step 2, patients will be randomized to the recommended dose of either CAPOXIRI+BEV or FOLFOXIRI+BEV. Induction triplet chemotherapy plus BEV treatments will be administered for up to 4 months followed by fluoropyrimidine plus BEV maintenance. The primary endpoint is progression-free survival (PFS). The similarity in PFS between the two arms will be evaluated by observing whether the point estimate of hazard ratio (HR) for PFS falls between 0.80 and 1.25. Ensuring a 70% probability that the observed HR will be "0.8 < HR < 1.25" under the assumption of the true HR of 1.0, and 100 patients will be evaluated during the 3-year study period. Secondary endpoints include overall survival, overall response rate, safety, and patient reported outcome (PRO) (FACT/GOG-Ntx4)., Discussion: Considering the lower incidence of hematologic toxicities with modified CAPIRI+BEV than with FOLFIRI+BEV, CAPOXIRI+BEV may be a promising treatment option if sufficient efficacy and lower hematologic toxicities are indicated in this study. Additionally, a lower incidence of peripheral sensory neuropathy (PSN) reported following CAPEOX treatment compared to that after FOLFOX in ACHIEVE, an adjuvant phase III trial, suggest that CAPOXIRI+BEV can mitigate OX-induced PSN., Trial Registration: Clinicaltrials.gov NCT04097444 . Registered September 20, 2019, https://clinicaltrials.gov/ct2/show/study/NCT04097444 / Japan Registry of Clinical Trials jRCTs041190072. Registered October 9, 2019.

A 70-year-old man presenting with melena was referred to our clinic. A clinical examination revealed a bulky tumor in the lower rectum. After ileostomy, 4 courses of capecitabine plus oxaliplatin (XELOX) therapy were administered as neoadjuvant chemotherapy. Computed tomography (CT) revealed significant reduction of the tumor. Laparoscopic super-low anterior resection with lateral lymph node dissection was performed. The pathological examination revealed no residual cancer cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 1 year after the operation. Neoadjuvant chemotherapy with XELOX might be promising for patients with locally advanced rectal cancer.

Gastrointestinal tract endoscopy revealed the presence of a 5-cm-diameter type 3 tumor in the cardiac portion of the stomach. The tumor was chromogranin positive, and stomach small cell cancer was diagnosed by immunostaining and biopsy pathology. S-1+CDDP therapy was administered as the first-line treatment. A switch to S-1 monotherapy was made after the patient experienced grade 4 hyponatremia. However, following 7 courses of therapy the disease had progressed. Second-line chemotherapy of CPT-11+CDDP was initiated and after 2 courses the disease stabilized.

A man in his fifties was referred to our hospital for anorexia and vomiting. Upper gastrointestinal endoscopy showed a gastric cancer (Borrmann Type 3) with pyloric stenosis. We performed gastrojejunostomy to allow oral intake for a tumor invading the pancreas head (cT4bN1H0P0CY1, Stage IV). After the operation, systemic chemotherapy with S-1 (120 mg/m²) was administered from July 2007, which caused grade 3 mucositis oral and drug rash after one week. Then, bi- weekly administration of CPT-11 (60 mg/m²) and CDDP (30 mg/m²) was started from August 2007 as second-line chemotherapy. The treatment was repeated for 14 courses till an allergic reaction happened. A weekly paclitaxel (PTX) therapy (80 mg/m²) was started from January 2009 as third-line. After 6 courses, CT showed that direct invasion to the pancreas was not clear any more, so a distal gastrectomy with D1 lymphadenectomy was performed on August 2009 (ypT3N- 1P0CY0, Stage IIB). The patient received 9 courses of weekly PTX therapy and after that the treatment has been discontinued. Recurrence was not observed for 48 months after an initial treatment.

We report a successful case with irinotecan (CPT-11 60 mg/m2) + cisplatin (CDDP 30 mg/m2) chemotherapy (once in 2 weeks) for recurrent gastric cancer of the remnant stomach. A 77-year-old man was performed a distal gastrectomy for duodenal ulcer 42 years ago. He had a total gastrectomy for gastric cancer of remnant stomach when he was at 73 years old. After the surgery, we treated this patient with S-1 mono-therapy for five courses. However, we finished this treatment for lymph-node metastases. Next we treated him with CPT-11 + CDDP. An abdominal CT revealed a CR after 6 courses. We finished this treatment after 12 courses for anemia (grade 3). After the treatment, the metastatic lymph-nodes appeared in no change. So we considered that CR was continued for 3.5 years.

A man in his fifties with rectal cancer underwent low anterior resection in another Hospital in January 2006. He was finally diagnosed with Stage III a (pA, pN1, H0, P0). The patient who had postoperative complication such as ruptured suture left the hospital in May 2006, when he was detected with multiple liver metastases and was referred to our hospital for systemic chemotherapy. Systemic chemotherapy with mFOLFOX6 was performed from May 2006. Grade 3 diarrhea and grade 2 peripheral neuropathy, nausea and vomiting were observed. After 6 courses of mFOLFOX6, MRI revealed metastasis had been disappeared and levels of CEA and CA19-9 were decreased below normal. The treatment has been discontinued. Recurrence was not observed for 30 months.

This case was a male patient, about 50 years old. He received a curative operation for advanced esophageal carcinoma [poorly differentiated squamous cell carcinoma type, Lt, pT3 (pAd) pN3, pstage III] in March 2005. He also received adjuvant chemotherapy of 5-FU plus cisplatin (CDDP). Fourteen months later (May 2006) from surgery, metastases to the left lung and left subclavian lymph nodes were diagnosed, so he received first-line triplet combination chemotherapy (NAF regimen; nedaplatin 60 mg/m2: day 1, adriamycin 50 mg/m2: day 1, 5-FU 700 mg/m2: day 1-5). According to the 9 courses of treatment of this regimen, complete response for these metastases was observed and first-line chemotherapy was finished. However, a severe headache appeared 3 months later, and he had a diagnosis of solitary 5 cm brain metastasis by MRI. Excision of the metastasis was performed with sequential whole-brain radiation therapy (30 Gy). Five months later, diffuse and multiple brain metastases relapsed, and second-line chemotherapy did not respond well, and finally he was died 3 months after palliative care. But, completely controlled metastases (lung and lymph node) by first-line chemotherapy did not relapse again in all his clinical period. If an anticancer therapy goes in complete response in an advanced esophageal carcinoma patient, we should consider about a rare brain metastasis in order to find out as small and solitary state.