Phase I Study of Combination Therapy With Weekly Nanoparticle Albumin-bound Paclitaxel and Cyclophosphamide in Metastatic Breast Cancer Patients.

BACKGROUND/AIM: The objective of this phase I study was to determine the maximum-tolerated dose (MTD) and recommended dose (RD) of combination therapy with weekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and cyclophosphamide (CPA) in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Five patients who had human epidermal growth factor receptor 2 (HER2) negative MBC were recruited in this study. They received nab-paclitaxel at dose levels of 100-150 mg once a week for three weeks, repeated every 4 weeks, and CPA (600 mg/m2) administered on day 1. RESULTS: No patient had grade 4 toxicity, however, two patients discontinued protocol treatment due to adverse events at level 2. Thus, the Data and Safety Monitoring Committee recommended the MTD of nab-paclitaxel and CPA to be determined at level 2. CONCLUSION: The combination therapy with weekly nab-paclitaxel and CPA was tolerable, and the RD for these drugs for MBC were 100 and 600 mg/m2, respectively.

Sudden development of adult-onset type II citrullinemia after total gastrectomy: a case report.

BACKGROUND: Adult-onset type II citurullinemia is an autosomal recessive disorder characterized by recurrent encephalopathy with hyperammonemia resulting from high plasma citrulline and ammonium levels. This report describes a rare case of adult-onset type II citurullinemia that occurred in a patient who only had the heterozygote mutation, and had never presented with any symptoms before surgery. CASE PRESENTATION: A 56-year-old man underwent a total gastrectomy for stomach cancer. On postoperative Day 13, he suddenly developed presyncope, and blood tests showed hyperammonemia and high levels of serum citrulline. He was diagnosed with hepatic encephalopathy. DNA analysis revealed a heterozygote mutation in Solute Carrier Family 25. Although the patient received a conservative treatment, episodes of loss of consciousness and abnormality of behavior repeatedly occurred. CONCLUSION: Abdominal surgery involving the reconstruction of digestive tract alters the mechanisms of absorption and/or metabolism such that the symptoms of adult-onset type II citurullinemia may arise. Liver transplantation should be performed if all conservative treatments are unsuccessful.

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.

[Efficacy and safety of cetuximab+irinotecan for unresectable advanced or recurrent colorectal cancer].

BACKGROUND: In July 2008, cetuximab treatment for unresectable advanced or recurrent colorectal cancer was approved in Japan, but there have been few reports on this therapy in Japan. PURPOSE: We retrospectively analyzed the efficacy and safety of cetuximab(Cmab)+irinotecan(CPT-11)for unresectable advanced or recurrent colorectal cancer from October 2008 to April 2010 at 5 centers in the Kanagawa region. PATIENTS AND METHODS: The number of patients enrolled was 38, all of whom were treated after second-line therapy. RESULTS: The RR was 24%. DCR was 68%. TTF was 105 days and OS was 242 days. CONCLUSION: At 5 centers, Cmab+CPT-11 was an effective and safe treatment after second-line therapy.

Self-expandable metallic stent placement for palliation in gastric outlet obstructions caused by gastric cancer: a comparison with surgical gastrojejunostomy.

BACKGROUND: In patients with gastric outlet obstruction (GOO), palliative enteral stenting is a less invasive procedure compared with gastroenterostomy. Most diseases analyzed in previous studies of such stenting were pancreaticobiliary malignancies. METHODS: We reviewed the medical records of patients with GOO secondary to gastric cancer who were admitted to our institution between September 1994 and September 2004. The outcome of stent placement for GOO was compared with the outcome in patients who underwent palliative open gastrojejunostomy during the same period. Enrolled patients from both groups displayed symptomatic GOO. Patients with recurrent gastric cancer were excluded from this study. RESULTS: Twenty-two patients underwent palliative enteral stenting, and 22 patients were subjected to surgical gastrojejunostomy (bypass). There were no significant differences between the two groups regarding patient baseline characteristics. Technical success and clinical success were obtained in 100% and 77.3%, respectively, of both groups. The operating time was shorter in the stent group (30 vs 118 min; P<0.0001). The time from the procedure to the resumption of food intake was shorter in the stent group than in the bypass group (2 days vs 8 days; P<0.0001). An improvement in performance score after the procedure was observed in both groups (stent group; P=0.0264; bypass group; P=0.0235). No significant differences were observed regarding the possibility of discharge. In patients discharged, the median postoperative hospital stays were 19 days and 28 days (P=0.0558). The median survival periods were 65 days and 90 days. Minor complications were observed in 1 patient in the stent group and in 4 in the bypass group. No mortality or severe complications were observed for either group. CONCLUSIONS: Self-expandable metallic stent placement is a safe and efficacious procedure for palliation, with shorter operating time and more prompt restoration of oral intake, compared to surgical alternatives in patients with GOO caused by gastric cancer.