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  • Hirano, Kenji  (7)
  • Tada, Minoru  (7)
  • Medicine  (7)
  • XA 52760  (7)
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 267-267
    Abstract: 267 Background: Here we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites. Methods: Paclitaxel was administered intravenous at 50 mg/m 2 and intraperitoneal at 20 mg/m 2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m 2 /day for 14 consecutive days, followed by 7 days rest. Results: Between April 2011 to February 2012, 10 patients were enrolled. A partial response was achieved in two (20%) and a disease control rate of 50%. The median time to progression and overall survival were 3.2 and 5.9 months, respectively. Malignant ascites was completely resolved in two (20%). Major grade 3/4 adverse events weremyelosuppression including neutropenia (50%) and catheter-related infection (10%). Conclusions: This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites. Clinical trial information: UMIN000005306.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 309-309
    Abstract: 309 Background: Non-anticancer drugs such as metformin or statin are reported to have a potential role in cancer treatment and we previously reported inhibition of renin-angiotensin system (RAS) by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) lead to better prognosis in PaC receiving gemcitabine (Br J Cancer 103: 1644-8). The relation between diabetes (DM) with its medication and the incidence of PaC has been described but its impact on prognosis is still unclear. Methods: We retrospectively reviewed 250 pts with advanced PaC receiving chemotherapy with gemcitabine and/or S-1 between June 2001 and April 2011 with a median follow up of 9.9 months (Mo). Univariate and multivariate analyses of progression-free survival (PFS) and overall survival (OS) were performed in pts with and without DM, using age, gender, BMI, PS, stage, protocol, DM with its treatment, hypertension (HT) with its treatment, and use of statin as variables. Results: DM was diagnosed in 124 pts (49%) and was treated with insulin or insulin analogs (n = 59), sulfonylurea (n = 38), biguanide (n = 8), thiazolidinedione (n = 6), and alpha-glucosidase inhibitor (n = 5). Statin was used in 16 pts with DM and 14 pts without DM. Locally advanced disease (44% vs. 29%) and HT (44% vs. 28%) were more prevalent in pts with DM. PFS (6.3 vs. 4.9 Mo, P = 0.440) and OS (13.3 vs. 10.0 Mo, P = 0.084) was longer in pts with DM, though not significantly. Use of statin in pts with DM was associated with longer PFS (11.6 vs. 6.0 Mo, P = 0.034) and longer OS (25.4 vs. 11.3 Mo, P = 0.006), while PFS and OS did not differ by the use of statin in pts without DM. Multivariate subgroup analysis with and without DM showed metastatic disease (Hazard ratio [HR] 2.11, P = 0.001 and HR 1.57, P = 0.013), PS 0-1 (HR 0.08, P 〈 0.001 and HR 0.21, P 〈 0.001), use of ACEI/ARB (HR 0.60, P = 0.030 and HR 0.46, P = 0.031) as common prognostic factors for OS. Doublet chemotherapy (HR 0.48, P = 0.007) and use of statin (HR 0.40, P = 0.010) were prognostic only in pts with DM, but any medications for DM were not significant prognostic factors. Conclusions: In our retrospective analysis, use of statin in pts with DM as well as inhibition of RAS was associated with better prognosis in pts with PaC receiving chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 298-298
    Abstract: 298 Background: Smoking is recognized as a risk factor for pancreatic cancer, but its associations with prognosis are not fully elucidated. Smoking was associated with poor outcomes in colon cancer, especially in patients with K-ras mutation (J Clin Oncol. 2013;31:2016-23). Therefore, we conducted this retrospective analysis of the associations of K-ras mutation, smoking and prognosis in patients with pancreatic cancer. Methods: Patients with pancreatic cancer who received surgery or chemotherapy at the University of Tokyo Hospital were retrospectively studied. The prognosis of patients with mutant and wild K-ras were compared. Overall survival was evaluated using Kaplan-Meier methods and compared by long-rank test. Cox regression models were used to calculate hazard ratios (HRs) to evaluate the prognostic factors in patients with pancreatic cancer with mutant K-ras or wild K-ras. Results: Between January 2009 and August 2013, K-ras mutation analysis was evaluated in 187 patients (47 surgical resection and 140 chemotherapy). K-ras mutation was detected in 74.3%. The rates of current-, ex- and never-smokers were 18.2%, 31.6% and 50.3%, respectively. In patients with mutant K-ras, the rate of male gender (46.0% vs. 29.0%), presence of distant metastasis (50.4% vs. 31.3%) and median CA19-9 (374 U/mL vs. 136 U/mL) were significantly higher than that in patients with wild K-ras. The rate of ever smokers (current- and ex-smokers) did not differ significantly (48.2% in mutant K-ras vs. 56.3% in wild K-ras, p=0.403). Median survival time (MST) was 16.7 (95%CI, 11.9-21.8) months in patients with mutant K-ras, compared with 20.3 (95%CI, 15.8-34.6) in patients with wild K-ras (p=0.193). Meanwhile, MST was 22.2 (95%CI, 16.9-27.9) vs. 14.8 (95%CI, 9.1-19.4) months in patients with and without smoking (p=0.024). After adjustment by age, gender, performance status, CA19-9 and treatment, HRs of smoking were 1.96 (95%CI, 1.06-3.68, p=0.032) in patients with mutant K-ras, but the association was not significant in patients with wild-K-ras (HR 1.35 [95%CI, 0.37-5.28], p=0.653). Conclusions: As previously reported in colon cancer, smoking was associated with poor prognosis in pancreatic cancer with K-ras mutation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 4_suppl ( 2013-02-01), p. 258-258
    Abstract: 258 Background: The data of second-line treatment for advanced biliary tract cancer is still limited. We have previously reported feasibility study of gemcitabine and cisplatin combination therapy for refractory biliary tract cancer (Sasaki T et al, Invest New Drugs 2011). In this feasibility study, only 20 pts were enrolled, and both second-line and third-line treatments were involved. Therefore, we conducted a retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment to clarify the treatment outcome of this combination therapy. Methods: Pts with advanced biliary tract cancer who were refractory to gemcitabine containing regimen were enrolled in this study. Gemcitabine 1,000 mg/m 2 and cisplatin 25 mg/m 2 were administered intravenously on days 1 and 8 repeated every 3 weeks. Results: Fifty-nine pts were enrolled in this study. Patient characteristics were: median age 68 (range 25-84); male/female 32/27; performance status 0/1/2 (15/38/6). The primary tumor site was; 24 pts in gallbladders, 18 pts in intrahepatic bile ducts, 15 pts in extrahepatic bile ducts, and 2 pts in ampulla of Vater. The numbers of the pts with locally advanced, metastatic, and recurrent cases were 8, 44, and 7, respectively. Four pts received gemcitabine monotherapy and 55 pts received gemcitabine and S-1 combination therapy as first-line treatment. Response rate and disease control rate were 1.7% and 56.0%, respectively. The median time-to-progression and median overall survival were 3.9 months (95%CI, 2.6 – 5.0 months) and 6.4 months (95%CI, 4.9 – 8.0 months), respectively. Conclusions: Gemcitabine and cisplatin combination therapy showed a moderate efficacy for the treatment of advanced biliary tract cancer as second-line treatment.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 290-290
    Abstract: 290 Background: Our previous randomized controlled trial, GEMSAP study (Br J Cancer. 2012 5;106:1934-9), showed a combination therapy of gemcitabine (Gem) & S-1 (GS) for advanced pancreatic cancer was superior to Gem monotherapy in terms of progression-free survival (PFS) but not overall survival (OS). Leucovorin (LV) is known to enhance efficacy of S-1 and we conducted this phase 1 trial of combination therapy of Gem, S-1 and LV (GSL). Methods: A primary endpoint of this classical “3+3” design phase 1 trial is to determine recommended dose of GSL. Inclusion criteria were 1. histologically-confirmed advanced pancreatic cancer without prior treatment, 2.PS 0-2, 3. age over 20. Treatment schedule was S-1 80 mg/m 2 2x p.o. days 1-7, LV50mg 2x p.o. days 1-7, Gem 600(Level1), 800(Level2), 1000 mg/m 2 (Level3) div 30-min day 1 in a 2-week schedule. Dose-limiting toxicities were Grade 4 hematological and Grade ≥3 non-hematological toxicities, or delay of recovery from treatment-related toxicity for more than 2 weeks. Results: Between May 2012 and Feb 2013, 15 patients (Level 1/2/3: 6/6/3 patients) were enrolled; 7 males, a median age of 66, PS 0/1: 5/10, locally advanced/metastatic: 5/10. DLT was observed in 2/6 in Level 1 (Grade 3 anorexia in 1 and Grade 3 anorexia/stomatitis/diarrhea in 1) and 1/6 in Level 2 (Grade 3 pulmonary embolism). No DLT was observed in Level 3 and RD was determined as 1,000 mg/m 2 of Gem. Tumor response by RECIST was PR 5, SD 9, NE 1 with response rate of 33% and disease control rate of 93%. Overall toxicities greater than 3 were neutropenia 20%, anemia 7%, anorexia 13%, diarrhea 7%, stomatitis 7% and pneumonitis 7%. Conclusions: RD of GSL was determined as GEM 1000 mg/m 2 div 30 min day 1, S-1 80 mg/m 2 2x, LV50mg 2x p.o. days 1-7. GSL was tolerable and showed promising tumor response in advanced pancreatic cancer. Clinical trial information: UMIN000007556.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e15216-e15216
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e15146-e15146
    Abstract: e15146 Background: Early response assessment is important to differentiate patients (pts) who will benefit from salvage chemotherapy (sCx) for refractory pancreatic cancer (PaC), given its palliative nature. CA19-9 has been reported as a prognostic factor in the first-line treatment, but little data is available in sCx. Methods: Pts receiving sCx for refractory PaC at the University of Tokyo Hospital were retrospectively studied. Serum CA19-9 was measured prior to the initiation of each course. Cumulative progression-free (PFS) and overall survival (OS) were calculated by Kaplan-Meier analysis and compared by log-rank test. Prognostic value of CA19-9 change prior to 2 nd course was evaluated using a landmark method. Finally, multivariate analyses by the Cox proportional hazard model were performed for PFS and OS. Possible prognostic factors were age, gender, PS, disease status, metastatic site, pretreatment albumin, LDH, CRP, CA19-9, CA19-9 change prior to 2 nd course, prior PFS, treatment line (2 nd line or beyond) and sCx agents. Results: A total of 167 pts (a median age of 65, 95 males, 21 recurrent and a median previous PFS of 5.8 Mo) received 239 regimens as sCx including S-1(n=87), CPT-11 (n=53), GEM+oxaliplatin(Ox) (n=20), S-1+Ox(n=29), GEM (n=14) and S-1+paclitaxel iv+ip (n=12). Median PFS and OS were 2.7 (95%CI, 2.4-3.1) and 6.1 (95%CI, 5.3-7.2) Mo, respectively. Early CA19-9 progression was defined as CA19-9 increase 〉 17.8%, a median value of CA19-9 change prior to 2 nd course in this study population. Median PFS and OS were 2.6 vs. 1.0 Mo and 7.5 vs. 3.6 Mo (p 〈 0.001) after landmark CA19-9 measurement in pts with and without CA19-9 response. Multivariate analyses demonstrated early CA19-9 progression was a negative prognostic factor of both PFS and OS (HR 1.75 and 2.04, p 〈 0.001). Pretreatment serum markers (albumin, LDH, CRP and CA19-9) were prognostic of OS, but not PFS. Conclusions: Early CA19-9 progression was a negative prognostic factor of both PFS and OS in S-Cx for refractory PaC. Early termination should be considered in these patients who would less likely benefit from sCx.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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