Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma

Haarst, J. M. W. Van; Baas, Paul; Manegold, Christian; Schouwink, J.H.; Burgers, Jacobus A.; Bruin, Hein G. de; Mooi, Wolter J.; Klaveren, R. J. van; Jonge, Maja J.A. de; Meerbeeck, Jan P. van

doi:10.1038/sj.bjc.6600118

Cited by 133 publications

(57 citation statements)

References 21 publications

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“…Cells (2x10 4 ) were seeded on a 96-well culture plate with the culture medium, and after overnight culture, the cells were treated with each agent. Following this, cell growth was determined with a cell proliferation assay kit using WST-1 reagent (Roche Japan, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

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Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

Kashiwagi

Virgona

Yamada

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Malignant mesothelioma (MM) is an aggressive cancer with no effective treatment options. Enforced expression of the gap junction (GJ) component connexin 43 (Cx43) increases the sensitivity of MM cells to cisplatin. BowmanBirk protease inhibitor (BBI) induces the restoration of Cx43 in several types of tumor cells. In this study, we examined the capability of BBI to enhance the cytotoxic effect of cisplatin in MM cells via the induction of Cx43. Human MM H28 cells were used. Cell viability was evaluated by a WST-1 assay and proteasomal activity was determined by fluorometric analysis. Protein and mRNA levels were determined by immunoblot analysis and real-time RT-PCR, respectively. GJ function mediated by Cx43 was evaluated using the scrapeloading method. BBI effectively inhibited H28 cell growth in a dose-dependent manner (200-400 µg/ml). In parallel with the growth inhibition, Cx43 levels (mRNA and protein) and GJ function were elevated by BBI treatment. Knockdown of BBI-induced Cx43 by an antisense nucleotide treatment almost cancelled the growth inhibition. BBI enhanced cisplatin-induced cytotoxicity in H28 cells, and down-regulation of Cx43 by the antisense nucleotide treatment abrogated the enhancing effect of BBI. The induction of Cx43 by BBI contributed to Src inactivation and subsequent induction of Bax. Furthermore, an Src inhibitor (SU6656) also enhanced cisplatin-induced cytotoxicity in H28 cells. These results suggest that BBI improves the cytotoxic efficacy of cisplatin in H28 cells via the inhibition of Src signaling.

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Section: Methodsmentioning

confidence: 99%

“…Cisplatin has been used in clinical MM therapy, and its chemotherapeutic effect as a single agent as well as in combination with other chemotherapeutic agents has been previously examined (3,4). However, most patients relapsed within 1 year after starting treatment.…”

Section: Introductionmentioning

confidence: 99%

Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

Kashiwagi

Virgona

Yamada

et al. 2011

Experimental and Therapeutic Medicine

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“…The high-dose regimen of gemcitabine and epirubicin had a confirmed response rate, median duration of response, median overall survival, and median time to disease progression that were comparable to other combination regimens, 10,12,22,23,26,27 but was found to have significant hematologic toxicity. Although the low-dose regimen had better hematologic toxicity, it was not found to have significant clinical activity against MPM.…”

Section: Discussionmentioning

confidence: 95%

“…[8][9][10] In addition, the anthracycline derivative epirubicin has been studied in patients with MPM, with a single-agent response rate of 15% and a median survival of 40 weeks. 11 When given in combination with cisplatin, the response rate was reported to be 19%, with a median survival of 13.3 months.…”

mentioning

confidence: 99%

A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma

Okuno

Delaune

Sloan

et al. 2008

Cancer

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BACKGROUND.The North Central Cancer Treatment Group (NCCTG) conducted a phase 2 study to evaluate the antitumor activity of the combination of gemcitabine and epirubicin in patients with pleural mesothelioma who received no more than 1 prior chemotherapy regimen.METHODS.A total of 23 patients were accrued between August 2001 and April 2002 and received gemcitabine at a dose of 1000 mg/m2 intravenously over 30 minutes weekly every 2 weeks and epirubicin at a dose of 90 mg/m2 intravenously on Day 1 on an every‐21‐days cycle (high‐dose patient group). Between August 2002 and April 2004, an additional 45 patients were treated at a reduced dose of gemcitabine of 750 mg/m2 and epirubicin at a dose of 70 mg/m2 with the same schedule (low‐dose patient group).RESULTS.In the high‐dose patient group, the confirmed response rate was 13% (95% confidence interval [95% CI], 3–34%). The median survival was 9.3 months (95% CI, 7.4–10.7 months) and the median time to disease progression was 6.3 months (95% CI, 3.0–7.6 months). In the low‐dose patient group, the confirmed response rate was 7% (95% CI, 0–28%). The median survival was 5.7 months (95% CI, 4.7–8.7 months) and the median time to disease progression was 4.2 months (95% CI, 2.7–5.6 months). Toxicity was moderate to severe. In the high‐doseand low‐dose groups, 87% and 60% of patients, respectively, experienced at least 1 adverse event of grade 4 or higher (according to National Cancer Institute Common Toxicity Criteria [version 2.0]). The quality of life remained similar from baseline to the end of the 2 cycles of treatment in the high‐dose group but worsened in the low‐dose group.CONCLUSIONS.In the current study, the combination regimen of gemcitabine and epirubicin was found to demonstrate minimal antitumor activity against pleural mesothelioma. Cancer 2008. © 2008 American Cancer Society.

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“…The combination of cisplatin plus gemcitabine was also evaluated in some phase II trials suggesting that it may be an alternative in patients not candidates to pemetrexed, despite heterogeneity between studies with response rates and survival ranging from 12-48% and 9.5-12 months, respectively (3,(27)(28)(29)(30)(31). Furthermore, the use of carboplatin with gemcitabine has been investigated showing good tolerance and a response rate of 26% (32).…”

Section: First-line Combination Ctmentioning

confidence: 99%

Chemotherapy treatment in malignant pleural mesothelioma: a difficult history

et al. 2018

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Malignant pleural mesothelioma (MPM) is a rare neoplasm that typically arises from mesothelial surfaces of the pleural cavity. Despite treatment improvements, it carries a dismal prognosis. The majority of patients either have unresectable disease or are not candidates for surgery due to medical comorbidities or old age. For such patients, chemotherapy (CT) represents the gold-standard treatment. To date, combination CT with cisplatin plus pemetrexed represents the most widely used regimen in first-line setting for patients with unresectable MPM. Other first-line options are currently available, including the use of raltitrexed instead of pemetrexed combined with platinum. In this review, we discuss the role of CT in MPM mainly focusing on the results of the trials conducted in first-line setting.

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Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma

Cited by 133 publications

References 21 publications

Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells

A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma

Chemotherapy treatment in malignant pleural mesothelioma: a difficult history

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