An Exploratory Phase II Study of Eribulin Re-challenge After Short Term Therapy of 5-Fluorouracil for HER2 Negative, Advanced or Recurrent Breast Cancer.

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.

Neoadjuvant Chemotherapy With Nab-paclitaxel Plus Trastuzumab Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide for HER2-positive Operable Breast Cancer: A Multicenter Phase II Trial.

AIM: This study was conducted in order to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus trastuzumab followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) in a neoadjuvant chemotherapy (NAC) setting for patients with human epidermal growth factor receptor 2 (HER2)-positive operable breast cancer. PATIENTS AND METHODS: Each patient received four cycles of 260 mg/m2 nab-paclitaxel with 6 mg/kg trastuzumab (8 mg/kg as the loading dose) every 3 weeks (q3w) followed by four cycles of FEC (500/100/500 mg/m2) q3w. The primary endpoint was pathological complete response (pCR) rate. RESULTS: Twenty-nine patients were analyzed for the efficacy and safety of this treatment. All patients completed four cycles of nab-paclitaxel and trastuzumab, and 28 patients completed four cycles of FEC. Twenty-seven patients subsequently underwent surgery. The pCR rate was 74.0%. The most frequent toxicity was sensory neuropathy (96.6%), but grade 3 neuropathy rate was 3.4%. CONCLUSION: Nab-paclitaxel plus trastuzumab followed by FEC in patients with HER2-positive operable breast cancer is considerably effective and well tolerated.

Meta-analysis of Robot-assisted Versus Laparoscopic Surgery for Rectal Cancer.

BACKGROUND/AIM: A meta-analysis was conducted to evaluate and compare the short- and long-term outcomes of robot-assisted (RAS) and conventional laparoscopic surgery (LAS) for rectal cancer. MATERIALS AND METHODS: We searched MEDLINE for relevant papers published between 2010 and December 2017 by using specific search terms. We analyzed outcomes over short- and long-term periods. RESULTS: We identified 23 papers reporting results that compared RAS for rectal cancer with LAS. Our meta-analysis included 4,348 patients with rectal cancer; 2,068 had undergone RAS, and 2,280 had undergone LAS. In the short- and long-term period, 27 and 7 outcome variables were examined, respectively. RAS for rectal cancer was significantly associated with a greater operative time and a lower conversion rate to open surgery in the short-term, and results in almost similar outcomes in the long-term, compared to LAS. CONCLUSION: RAS may be an acceptable surgical treatment option compared to LAS for rectal cancer.

Safety and Efficacy of Low-dose Nanoparticle Albumin-bound Paclitaxel for HER2-negative Metastatic Breast Cancer.

BACKGROUND/AIM: Nab-paclitaxel (nab-PTX) is an albumin-bound paclitaxel formulation. Although nab-PTX has shown superior efficacy compared to conventional paclitaxel (PTX) in metastatic breast cancer (MBC), chemotherapy-induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In this study, we aimed to estimate the feasibility of the nab-PTX 175 mg/m2/3weeks regimen. PATIENTS AND METHODS: Patients having metastatic or inoperable HER2-negative breast cancer received 175 mg/m2 of nab-PTX every three weeks. The primary endpoint was safety and the secondary endpoints were response and survival. RESULTS: Seventeen patients were enrolled with a median age of 64 years. Ten patients had estrogen receptor positive disease and seven had triple-negative disease. CIPN was observed in seven patients (41%) however, grade 3 CIPN was only seen in one patient (6%). Objective response rate was 41% and progression-free survival was 23 weeks. CONCLUSION: Nab-PTX 175 mg/m2/3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment.

Phase I study of nanoparticle albumin-bound paclitaxel, carboplatin and trastuzumab in women with human epidermal growth factor receptor 2-overexpressing breast cancer.

Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study. Based on these results, a phase I study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was planned, in order to estimate its efficacy and safety for HER2-overexpressing locally advanced breast cancer. The present study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this combination treatment in women with HER2-overexpressing locally advanced breast cancer. The starting dose of nab-paclitaxel was 220 mg/m2 (level 1), and the dose was escalated to 260 mg/m2 (level 2). Nab-paclitaxel was administered with carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A total of 6 patients were enrolled. Although no DLT was observed during the first cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I study, although no patients experienced DLTs, this regimen was associated with severe hematological toxicities and it was not well tolerated. However, considering the high efficacy and lower risk of cardiotoxicity and secondary carcinogenesis with taxane, platinum and trastuzumab combination therapy, further evaluation of another regimen including weekly administration or a more accurate dose setting should be conducted.

A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer.

The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

[Two cases of esophageal variceal rupture associated with chemotherapy for liver metastasis of breast cancer].

A morphological change resembling liver cirrhosis called pseudocirrhosis may be observed following chemotherapy for liver metastasis of breast cancer. Pseudocirrhosis is hypothesized to be caused by retraction of the hepatic capsule along with tumor shrinkage and subsequent scar formation around the metastatic lesion, as a response to the infiltrating tumor or chemotherapy-induced hepatic injury. The progression of cirrhotic changes may result in portal hypertension and esophageal varices. We managed two cases of esophageal variceal rupture during chemotherapy for breast cancer with liver metastasis. Hemostasis was successfully achieved by the endoscopic variceal ligation technique in both cases. We conclude that clinicians should be aware of the risk of pseudocirrhosis during chemotherapy for liver metastasis, and a periodic endoscopic follow-up is recommended along with appropriate management of esophageal varices.

[A case of solitary adrenal metastasis from breast cancer successfully resected by laparoscopy].

A 47-year-old woman had undergone breast-conserving treatment for right breast cancer (T3, N1, M0, Stage IIIA, human epidermal growth factor receptor[ HER]-2 enriched subtype) after primary systemic chemotherapy with trastuzumab. Pathological examination revealed a quasi-pathological complete response( CR) in the breast tumor and no axillary nodal involvement. The patient then received conventional breast irradiation and adjuvant trastuzumab therapy. However, adjuvant anti- HER2 therapy was discontinued in the 19th week because of a decreased left ventricular ejection fraction( approximately 50%). A left adrenal tumor was detected by abdominal computed tomography (CT) 2 years after surgery. Positron emission tomography( PET) scans showed strong accumulation in the left adrenal gland and in the lymph node near the adrenal tumor. No other obvious lesion was detected on meticulous examination. Laparoscopic adrenalectomy was performed for diagnosis and treatment. Pathological examination of the resected specimen revealed that the tumor was a metastatic adenocarcinoma with overexpression of the HER2 protein but without expression of hormonal receptors. The patient received 12 cycles of chemotherapy with paclitaxel and trastuzumab, which was followed by trastuzumab monotherapy. However, trastuzumab monotherapy could not be continued because the left ventricular ejection fraction decreased to 50% at 24 weeks after initiation of chemotherapy. The patient has been observed since the cessation of trastuzumab, without the administration of anticancer therapy, and she continues to have a good performance status without relapse. Herein, we report a case of solitary adrenal metastasis from breast cancer, an extremely rare condition, and review the relevant literature.

[A long-term survival case of unresectable intrahepatic cholangiocarcinoma treated with chemotherapy].

An 83-year-old man commuting to our hospital with postoperative ascending colon cancer was pointed out an increase of CA19-9. CT scan revealed an intrahepatic cholangiocarcinoma in the left lobe. In May 2007, an operation was performed. We recognized a lymph node swelling in the hepatoduodenal ligament. Pathologically, it was moderately differentiated adenocarcinoma. Therefore, the operation did only the cholecystectomy. Gemcitabine was administered once a week for 3 weeks followed by a week rest. It was administered for about 20 months and the evaluation during the period was PR or SD. Afterwards, the tumor had increased gradually. Gemcitabine was changed to S-1. Then, S-1 was changed to gemcitabine again because the enlargement of the tumor and the rise of tumor markers were observed. Consequently, tumor markers decreased. Now, the patient is under an outpatient care maintaining ADL.

[Case of advanced gastric cancer successfully treated with chemotherapy of weekly paclitaxel].

We report a case of gastric cancer with ascites treated with chemotherapy. The patient is a 67-year-old male. Combination chemotherapy of S-1 and CDDP was given as the first-line treatment. However, the symptoms did not improve with that regimen, so we decided to change the chemotherapy to paclitaxel as second-line treatment. After 4 cycles, CT scan revealed decreasing ascites and endoscopy a reduction of the primary tumor. The patient has maintained a condition of decreasing ascites with improvement of QOL for 8 months. This regimen is considered effective treatment for unresectable gastric cancer.