Kenji Higaki

Safety and efficacy of gemcitabine and trastuzumab in HER2-directed therapy pretreated patients with HER2-positive metastatic breast cancer: SBP-01 study.

142 Background: Prognosis of HER2-positive metastatic breast cancer (MBC) has been dramatically improved by trastuzumab (Tmab). More recently, newer anti-HER2 agents such as lapatinib, pertuzumab and T-DM1 have prolonged survival. Despite the efficacy of these drugs, most patients develop progressive disease during or after treatment, and alternative anti-HER2 agents plus chemotherapies are required in subsequent lines of treatment. However, there are few evidence on efficacy of Tmab-containing regimens after disease progression. Gemcitabine (GEM) is non-cross resistant to anthracycline and taxane. Preclinical studies have shown that the combination of Tmab and GEM has synergistic effect against HER2-positive breast cancer cell lines. SBP-01 study assessed the efficacy and safety of the combination of Tamb and GEM in patients with HER2-positive MBC previously treated with anti-HER2 therapy. METHODS SBP-01 study included patients treated with one or more anti-HER2 directed regimens for MBC. Patients were administered with GEM 1250 mg/m2 on days 1 and 8 of each 21-day cycle and Tmab 4mg/kg loading dose and then 2mg/kg weekly. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival, and safety. RESULTS Between June 2011 and June 2014, 35 patients were enrolled. Patients had ER positive tumor (37.1%), a median of 2 metastatic organ sites, visceral metastasis (80.0%), prior (neo) adjuvant Tmab (22.9%) and a median of 2 prior chemotherapy regimens for MBC. Previous HER2-directed drugs included Tmab (94.3%), lapatinib (37.1%), T-DM1 (8.6%) and pertuzumab (2.9%). ORR was 22.9% (95% CI, 8.6%-36.8%). Median PFS was 146 days. Patients with stable disease response received a median of 7 cycles (6-28 cycles) of treatment. Grade3/4 leukopenia (20.0%) and neutropenia (48.6%) were observed. All non-hematological toxicities were less than grade3. CONCLUSIONS The Combination Tmab and GEM is effective and well-tolerated regimen for patients previously treated with HER2-directed therapy, and appears to make disease stable for long time period. CLINICAL TRIAL INFORMATION UMIN000005881.

Effects of Alcohol Containing Onetaxotere® on Patients

ドセタキセルは乳がん,非小細胞肺がん,胃が ん,頭頸部がん,卵巣がん,子宮体がん,食道が ん,前立腺がんなど様々ながん腫に対して適応を 取得している.従来のドセタキセル製剤である タキソテール(TXT)は,ポリソルベート 80 を可溶化剤として使用した原液,さらに 95%エ タノールを主成分とする添付溶解液の 2 つから構 成されている.TXT の調製は,通常この添付溶解 液に混和し,その後均一な液体が得られるまでに 数分間の放置が必要である など,時間を要する 作業であった.その問題点を改善するため発売さ れたワンタキソテール(OTX)は,無水エタノ ールを予め含有しており,プレミックスを必要と しない製剤である.この改善により,OTX の調 製時間は TXT と比較し約 7 分短縮できるとされて いる.しかし,OTX は TXT と比較し 2 倍以上の アルコールを予め含有しており(表 1),OTX 投 与患者はアルコールによる影響が懸念される.タ

CLINICOPATHOLOGICAL ANALYSIS OF GASTRIC MUCOSAL CANCER INVADING LYMPH VESSELS OR THE VEINS OF THE STOMACH WALL

In total, 573 lesions were resected from 518 patients with primary gastric mucosal cancer in Hiroshima City Hospital over the last 20 years, and the patients with ly(+) or v(+) lesions were analyzed from the clinicopathological point of view. The results were as follows. 1) 17 patients (3.0%) had ly(+) lesions, 3 (0.6%) had v(+) lesions. 2) In all but one case the lesions were located in the M or A area. 3) In all cases except two the lesions were depressed or mixed type. 4) Although one lesion was pap, the others were sig or tub 1, 2. However, there were no significant differences between the differentiated and undifferentiated types. 5) The maximal tumor diameter ranged from 1.5cm in the n(+) cases, but in the ly(+) cases from 0.7cm less than those cases. 6) 12 patients had n(+). Although 7 of the latter had ly(+), there were 3 n(+) cases even among the ly(-) cases. Furthermore, the 10 cases had depressive compartment. 7) Two patients died of another disease and one died of bone metastasis. The other patients are all alive. These results indicate that gastrectomy with node dissection should be done for the depressed or mixed type of lesion which has the possibility of being not only n(+) but also ly(+), v(+) even in the case of mucosal cancer.

CLINICAL SIGNIFICANCE OF TUMOR MARKERS IN BREAST CANCER

CA15-3, NCC-ST-439, BCA225 and CEA were measured in patients with breast cancer and the clinical significance of the these tumor markers were studied on. In primary breast cancers, the positive rates of them were 11_??_14%. With an advance in the stage of the disease, the positive rate for each marker increased, but in stages I and II the positive rate was low, indicating that these markers were unsatisfactory for screening. In recurrent cases following surgery for breast cancer, all the tumor markers showed a positive rate higher than that in non-recurrent cases. The positive rates of tumor markers at the time when definite diagnosis of recurrent cancer was made were high in the liver and bone, but low in lymph nodes, skin and thoracic wall. Organ specificity of these tumor markers could not be confirmed. The positive rates in recurrent breast cancers increased with combination assay, suggesting that tumor marker determination is extremely useful for postoperative screening. In particular, the positive rates of CEA and CA15-3 showed the highest value of 66.0% and the correlation was also, low, indicating that the combination is satisfactory.