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      Retrospective Clinical Study of Advanced Pancreatic Cancer Treated With Chemotherapy and Abdominal Hyperthermia

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          Abstract

          Purpose

          Hyperthermia is a mechanistically plausible partner with chemotherapy, although many of the underlying molecular mechanisms of this combination treatment are not yet properly understood. Preclinical studies suggest that there is potential synergy with gemcitabine and that provides the basis for retrospective analysis of a clinical series combining these treatment modalities for patients with advanced pancreatic cancer.

          Patients and Methods

          Twenty-nine chemotherapy-naive patients with locally advanced or metastatic pancreatic carcinoma with malignant ascites were treated with intraperitoneal cisplatin 30 mg/m 2 and gemcitabine 800 to 1,000 mg/m 2 intravenously on days 1, 8, and 15 every 28 days until tumor progression. Patients also received regional hyperthermia treatment (41 to 42°C) on the upper abdomen two times per week from days 1 to 21.

          Results

          In all, 83 cycles of chemotherapy were administered and were generally well tolerated. No patients had a complete response, 13 had a partial response, seven had stable disease, and 9 had progressive disease. Mean progression-free survival and overall survival were 119 ± 61days and 195 ± 98 days, respectively.

          Conclusion

          This study provides preliminary evidence that the treatment approach of combined systemic and intraperitoneal chemotherapy plus hyperthermia is well tolerated, is active, and has an acceptable survival profile for patients with stage IV pancreatic cancer and ascites.

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          Most cited references10

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          Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer.

          Intravenous platinum-based chemotherapy is the standard primary therapy for advanced ovarian cancer. We conducted a phase 3 trial to compare the effects of intraperitoneal and intravenous cisplatin on the survival of women with previously untreated, stage III, epithelial ovarian cancer. The patients underwent an initial exploratory laparotomy and resection of all tumor masses larger than 2 cm. Within four weeks after surgery, six courses of intravenous cyclophosphamide (600 mg per square meter of body-surface area per course) plus either intraperitoneal cisplatin (100 mg per square meter) or intravenous cisplatin (100 mg per square meter) were administered at three-week intervals. Of 654 randomized patients, 546 were eligible for the study. The estimated median survival was significantly longer in the group receiving intraperitoneal cisplatin (49 months; 95 percent confidence interval, 42 to 56) than in the group receiving intravenous cisplatin (41 months; 95 percent confidence interval, 34 to 47). The risk of death was lower in the intraperitoneal group than in the intravenous group (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Moderate-to-severe tinnitus, clinical hearing loss, and neuromuscular toxic effects were significantly more frequent in the intravenous group. As compared with intravenous cisplatin, intraperitoneal cisplatin significantly improves survival and has significantly fewer toxic effects in patients with stage III ovarian cancer and residual tumor masses of 2 cm or less.
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            National cancer incidence and mortality in China, 2012.

            Population-based cancer registration data in 2012 from all available cancer registries were collected by the National Central Cancer Registry (NCCR). NCCR estimated the numbers of new cancer cases and cancer deaths in China with compiled cancer incidence and mortality rates.
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              Non-anthracycline-containing docetaxel and cyclophosphamide regimen is associated with sustained worse outcome compared with docetaxel, anthracycline and cyclophosphamide in neoadjuvant treatment of triple negative and HER2-positive breast cancer patients: updated follow-up data from NATT study

              Objective A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide (TC) regimen was inferior to docetaxel, anthracycline and cyclophosphamide (TAC) in neoadjuvant treatment of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2-(HER2)-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated. Methods TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission (pCR). Secondary endpoints included clinical response rate, event-free survival (EFS), and overall survival (OS). Results A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of 53 (range, 8–76) months, the patients achieving pCR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without pCR (P<0.05). TAC treatment resulted in consistently better EFS than TC treatment: the estimated 5-year EFS was 66.1% vs. 29.8% (P=0.002). Moreover, the estimated 5-year OS was also in favor of TAC: 88.4% vs. 51.6% (P<0.001). Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.26–0.90; P=0.021] and OS (HR, 0.20; 95% CI, 0.08–0.60; P=0.003). Conclusions The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.
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                Author and article information

                Journal
                J Glob Oncol
                J Glob Oncol
                jgo
                jgo
                JGO
                Journal of Global Oncology
                American Society of Clinical Oncology
                2378-9506
                2018
                25 July 2017
                : 4
                : JGO.2017.009985
                Affiliations
                [1] Yu-Fei Fan, Beijing Yanhua Hospital; Yuan Qin and Ding-Gang Li, Beijing Haidian Hospital, Beijing, China; and David Kerr, University of Oxford, Oxford, United Kingdom.
                Author notes
                Corresponding author: David Kerr, MD, DSc, University of Oxford, Nuffield Department of Clinical Laboratory Science, Academic St, Level 4, John Radcliffe Hospital, Oxford, OX15 0QN, United Kingdom; e-mail: david.kerr@ 123456ndcls.ox.ac.uk .
                Article
                009985
                10.1200/JGO.2017.009985
                6180841
                30241198
                a05f2173-5fea-4200-9121-652067e336b0
                © 2017 by American Society of Clinical Oncology

                Licensed under the Creative Commons Attribution 4.0 License: http://creativecommons.org/licenses/by/4.0/

                History
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 11, Pages: 4
                Categories
                Diagnosis & Staging
                ORIGINAL REPORTS
                Gastrointestinal Cancer
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                v1

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