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

Naiki, Taku; Iida, Kei; Kawai, Noriyasu; Etani, Toshiki; Ando, Ryosuke; Nagai, Takashi; Tanaka, Yutaro; Hamamoto, Shuzo; Hamakawa, Takashi; Akita, Hidetoshi; Sugiyama, Yosuke; Yasui, Takahiro

doi:10.2185/jrm.2940

Cited by 3 publications

(2 citation statements)

References 20 publications

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“…Recently, mechanisms of acquisition of chemoresistance to gemcitabine in urothelial cancer cells have been outlined. 23 , 24 However, gemcitabine shows a synergistic effect when combined with different chemotherapeutic agents, and several studies have consistently used gemcitabine in sequential therapy, 25 , 26 as in our chemotherapeutic strategies for mUC. As a result, GD therapy after the failure of gemcitabine and platinum-based combination therapy showed good anti-tumor effects: the total ORR waŝ20% and the median OS was 7.6 months for the entire cohort receiving second-line GD therapy.…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis

Naiki¹,

Iida²,

Etani³

et al. 2018

CMAR

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BackgroundThe objective of this study was to evaluate the efficacy of a combination of gemcitabine and docetaxel (GD) as a second-line treatment for elderly patients with metastatic urothelial carcinoma (mUC).Patients and methodsA total of 122 patients with mUC who were previously treated with platinum-based chemotherapy received second-line GD therapy from July 2010 to June 2016. This consisted of 800 mg/m2 gemcitabine and 40 mg/m2 docetaxel on days 1 and 8 in each 21-day cycle. Using pooled cumulative data, we divided patients into the following three groups based on age: <65 years (Group A), from 65 to 74 years (Group B), and ≥75 years (Group C), and then the data were retrospectively analyzed. All patients were evaluated for treatment-related toxicities and assessed at every cycle by imaging studies. Kaplan–Meier curves were used for survival and recurrence analyses. Furthermore, potential prognostic factors for progression-free survival (PFS) and overall survival (OS) were assessed via univariate and multivariate Cox regression analyses.ResultsThe median follow-up period was 8.2 months (range: 2.1–100). The median number of treatment cycles was three (range: 1–16) in Group A, three (1–15) in Group B, and two (1–11) in Group C. The objective response rate was not significantly different between the three groups. In addition, PFS and OS from the start of second-line GD therapy were also not significantly different. According to univariate and multivariate analyses of the second-line GD-treated cohort, a good performance status was the only prognostic factor for PFS and OS. In Group C, myelosuppression including predominant neutropenia and anemia, fatigue, and nausea were the main common adverse events. However, the incidence of neutropenia and a reduction in platelets were not significantly different between the three groups. Treatment-related deaths did not occur in this study.ConclusionIn this study, GD combination therapy as a second-line treatment for mUC resulted in favorable tumor responses and few treatment-related toxicities, even among elderly patients.

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Section: Discussionmentioning

confidence: 99%

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis

Naiki¹,

Iida²,

Etani³

et al. 2018

CMAR

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“…However, there are few reports on the improvement of QoL with second-line chemotherapy in patients with platinum-resistant UC with a PS of 2 or 3. It has been reported that in patients with platinum-resistant UC, two cycles of combination therapy (gemcitabine 1,000 mg/m 2 on days 1, 8, and 15, and paclitaxel 200 mg/m 2 on day 1 of each 21-day cycle) did not significantly improve scores on all items of the SF-36 (20). However, in that study, this regimen was used in the third-line setting and the study population did not include patients with PS 2 or 3.…”

Section: Relationship Between Overall Survival Periods and Expressimentioning

confidence: 95%

Four-weekly Low-dose Gemcitabine and Paclitaxel in Patients With Platinum-resistant Urothelial Cancer and Performance Status 2/3

Araki

Miyata

Nakamura

et al. 2019

In Vivo

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Background/Aim: Immune checkpoint inhibitors are often unsuitable for patients with urothelial cancer with a poor performance status (PS 2 or 3). The aim of this study was to assess the safety and usefulness of combined therapy with low-dose gemcitabine and paclitaxel every 4 weeks. Patients and Methods: Thirty patients were treated with gemcitabine (700 mg/m 2 on day 1) and paclitaxel (70 mg/m 2 on day 1) every 4 weeks. The predictive value of human antigen-R (HuR) and class III β-tubulin (TUBB3) were also analyzed. Results: There was no severe adverse event nor significant decrease in quality of life. The survival period of patients treated with this regimen was significantly longer than that of those treated with best supportive care. The expression pattern of HuR negativity and TUBB3 positivity predicted significantly worse overall survival. Conclusion: Our regimen was suitable as second-line therapy for patients with advanced platinum-resistant UC with a poor PS. However, a HuR-negative and TUBB3-positive expression pattern appears to confer poorer outcome.

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Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder

et al. 2018

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Metastatic urothelial carcinoma of the bladder is a rarely curable disease. Patients receive systemic therapy with limited response rates and survival benefits. The rescue regimens of these patients who have failed first-line treatment had remained problematic until the recent advances. Several trials with novel regimens, including immune checkpoint inhibitors and targeted therapy, to salvage relapsed urothelial carcinoma of the bladder have recently been published. However, the choice of an optimal treatment regimen remains challenging in the absence of randomized trials comparing regimen sequences. Daily clinical cases provoke the question of whether there is a preferred second-line regimen. This paper provides an overview of recent trials and proposes a management algorithm based on subgroup analyses and prognostic features.

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

Cited by 3 publications

References 20 publications

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis

Four-weekly Low-dose Gemcitabine and Paclitaxel in Patients With Platinum-resistant Urothelial Cancer and Performance Status 2/3

Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder

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