Paclitaxel and cisplatin chemotherapy for metastatic urothelial carcinoma after failure of two courses of platinum‐based regimens

Joung, Jae Young; Kwon, Whi‐An; Cho, In-Chang; Kim, Min Jung; Park, Sohee; Yoon, Hye-Kyoung; Seo, Ho Kyung; Chung, Jinsoo; Park, Weon Seo; Lee, Kang Hyun

doi:10.1111/j.1442-2042.2011.02735.x

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…of RR patients (%) MedianPFS (months) MedianOS (months) Soga et al 12 ) carboplatin/paclitaxel gemcitabine 13 1 (7.7) 8 (61.5) 2.0 7.3 Joung et al 13 ) MVAC, or GC paclitaxel/cisplatin 21 3 (14.3) 9 (42.9) 3.0 9.0 Rozzi et al 14 ) carboplatin/paclitaxel, or paclitaxel PLD 23 3 (13.0) 10 (43.5) 4.1 6.3 Matsumoto et al 15 ) gemcitabine/paclitaxel gemcitabine/nedaplatin 10 1 (10.0) 4 (40.0) 5.0 8.8 Iida et al 16 ) gemcitabine/docetaxel pemetrexed 4 0 (0) 0 (0) 1.9 – <...>…”

Section: Discussionmentioning

confidence: 99%

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A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma

et al. 2017

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Background: We evaluated the effectiveness of gemcitabine and paclitaxel therapy in patients with metastatic urothelial carcinoma for whom two lines of sequential chemotherapy had been unsuccessful.Methods: A total number of 105 patients who had previously received first-line chemotherapy consisting of gemcitabine and cisplatin or carboplatin, were treated with second-line gemcitabine and docetaxel therapy between June 2006 and May 2015. Of these patients, 15 with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 were administered gemcitabine and paclitaxel as third-line treatment from 2013 after failure of the second-line therapy. For each 21-day cycle, gemcitabine (1000 mg/m2) was administered on days 1, 8, and 15, and paclitaxel (200 mg/m2) on day 1. Patients were assessed for each cycle and any adverse events were noted. Furthermore, a Short Form Health Survey questionnaire was used to assess each patient’s quality of life.Results: Third-line gemcitabine and paclitaxel treatment cycles were undertaken for a median of four times (range 2–9). The disease control rate was 80.0%. After second-line gemcitabine and docetaxel therapy was completed, median progression-free survival and median overall survival were determined as 9.8 and 13.0 months, respectively. The only prognostic factor for overall survival, as determined by univariate and multivariate analyses, was third-line gemcitabine and paclitaxel therapy. Neutropenia (66.7%) and thrombocytopenia (53.3%) were noted as the grade 3 treatment-related toxicities. After two cycles of third-line gemcitabine and paclitaxel therapy, the pre- and post-treatment quality of life scores did not differ significantly.Conclusions: Results demonstrate that third-line combination therapy using gemcitabine and paclitaxel is a feasible option for metastatic urothelial carcinoma patients.

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Section: Discussionmentioning

confidence: 99%

“…However, only Joung et al . 14 ) described a case of CR. We, therefore, evaluated tumor control according to the proportion of PR and SD cases to the total number of cases.…”

Section: Discussionmentioning

confidence: 99%

A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma

et al. 2017

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“…The vast majority of patients treated with CDDP-based regimens develop progressive disease within 8 months of treatment, and the median survival is reported to be only 13–15 months [ 2 , 16 ]. Furthermore, there is still no approved treatment option for patients who develop disease recurrence or progression after CDDP-based regimens [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of NF kappa B activation is an effective therapeutic modality in acquired platinum-resistant bladder cancer

et al. 2015

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BackgroundNo previous study has addressed the efficacy of NF-κB blockade when bladder tumors develop acquired resistance toward CDDP-treatments. We investigated the changes in NF-κB activation and therapeutic impact of NF-κB blockade by the novel NF-κB inhibitor dehydroxymethyl derivative of epoxyquinomicin (DHMEQ) in CDDP-resistant bladder cancer cells.MethodsTwo human invasive bladder cancer cell lines, T24 and T24PR, were used. The T24PR cell line was newly established as an acquired platinum-resistant subline by culturing in CDDP-containing medium for 6 months. Expression of intranuclear p65 protein in the fractionated two cell lines was determined by Western blotting analysis. DNA-binding activity of NF-κB was detected by electrophoretic mobility shift assay. The cytotoxic effects and induction of apoptosis were analyzed in vivo and in vitro.ResultsIntranuclear expression and DNA-binding activity of p65 were strongly enhanced in T24PR cells compared with those of T24 cells, and both were significantly suppressed by DHMEQ. Lowered cell viability and strong induction of apoptosis were observed by treatment with DHMEQ alone in these chemo-resistant cells compared with parent cells. As T24PR cells did not show dramatic cross-resistance to paclitaxel in the in vitro study, we next examined whether the combination of DHMEQ with paclitaxel could enhance the therapeutic effect of the paclitaxel treatment in T24PR tumors. Using mouse xenograft models, the mean volume of tumors treated with the combination of DHMEQ (2 mg/kg) and paclitaxel (10 mg/kg) was significantly smaller than those treated with paclitaxel alone (p < 0.05), and the reduction of tumor volume in mice treated with DHMEQ in combination with paclitaxel and paclitaxel alone as compared to vehicle control was 66.9% and 17.0%, respectively.ConclusionThere was a distinct change in the activation level of NF-κB between T24 and T24PR cells, suggesting strong nuclear localization of NF-κB could be a promising target after developing acquired platinum-resistance in bladder cancer.

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“…This study is dealing with an important subject in the management of metastatic bladder cancer, which is: what is next after failure of two consecutive courses of chemotherapy? 1 It is clear that the main goals of any further management for these cases should involve an increase in the disease-specific survival and the improvement of quality of life. However, in this project, these issues were not completely covered.…”

Section: Editorial Comment To Paclitaxel and Cisplatin Chemotherapy Fmentioning

confidence: 99%

“…1 It is clear that the main goals of any further management for these cases should involve an increase in the disease-specific survival and the improvement of quality of life. However, in this project, these issues were not completely covered.…”

Section: Editorial Comment To Paclitaxel and Cisplatin Chemotherapy Fmentioning

confidence: 99%

Editorial Comment to Paclitaxel and cisplatin chemotherapy for metastatic urothelial carcinoma after failure of two courses of platinum‐based regimens

El‐Gamal

2011

Int J of Urology

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Paclitaxel and cisplatin chemotherapy for metastatic urothelial carcinoma after failure of two courses of platinum‐based regimens

Cited by 10 publications

References 24 publications

A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma

A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma

Down-regulation of NF kappa B activation is an effective therapeutic modality in acquired platinum-resistant bladder cancer

Editorial Comment to Paclitaxel and cisplatin chemotherapy for metastatic urothelial carcinoma after failure of two courses of platinum‐based regimens

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