scholarly journals Systematic Review and Meta-Analysis of Cisplatin Based Neoadjuvant Chemotherapy in Muscle Invasive Bladder Cancer

2021 ◽  
pp. 1-13
Author(s):  
Raed Benkhadra ◽  
Tarek Nayfeh ◽  
Sai Krishna Patibandla ◽  
Chelsea Peterson ◽  
Larry Prokop ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Efficacy And Safety ◽  
Muscle Invasive Bladder Cancer ◽  
Increased Risk ◽  
Muscle Invasive

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC). OBJECTIVE: To compare the efficacy and safety of the two most commonly used cisplatin-based regimens; gemcitabine, and cisplatin (GC) vs. accelerated (dose-dense: dd) or conventional methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). METHODS: We searched MEDLINE, Embase, Scopus and other sources. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. RESULTS: We identified 24 studies. Efficacy outcomes were comparable between MVAC and GC for MIBC. dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95%CI 1.15–1.82) and all-cause mortality at longest follow-up (OR 0.63; 95%CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95%CI 0.13–0.80), anemia (OR 0.32; 95%CI 0.18–0.54), nausea and vomiting (OR 0.27; 95%CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95%CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95%CI 0.01–0.31). Certainty in the estimates was very low for most outcomes. CONCLUSIONS: Efficacy and safety outcomes were comparable between MVAC and GC for MIBC. Including non-peer-reviewed studies showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice.

Methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) versus gemcitabine, and cisplatin (GC) as neoadjuvant chemotherapy in muscle-invasive bladder cancer, a systematic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16522-e16522
Author(s):  
Raed Benkhadra ◽  
Tarek Nayfeh ◽  
Naga Sai Krishna Patibandla ◽  
Chelsea Peterson ◽  
Larry Prokop ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Efficacy And Safety ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

e16522 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC) in cisplatin-eligible patients. This systematic review and meta-analysis provide an updated efficacy and safety comparison between the two most commonly used cisplatin-based regimens; dose-dense (dd) or conventional MVAC versus GC. Methods: We searched different databases for studies comparing MVAC versus GC in the neoadjuvant setting. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. Results: We identified 24 studies from inception to March 2020; among them 17 were peer reviewed and 7 were only reported as abstracts in national or international meetings, including a phase 3, randomized-controlled clinical trial. Among peer-reviewed published studies, efficacy outcomes such as OS, downstaging and pCR were comparable between conventional MVAC and GC for MIBC. If including non-peer-reviewed studies, dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95% CI 1.15–1.82), and OS at longest follow-up (OR 0.63; 95% CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95% CI 0.13–0.80), anemia (OR 0.32; 95% CI 0.18–0.54), nausea and vomiting (OR 0.27; 95% CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95% CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95% CI 0.01-0.31). Certainty in the estimates was very low for most outcomes. Conclusions: Among peer-reviewed published studies, efficacy and safety outcomes were comparable between conventional MVAC and GC for MIBC. However, If including non-peer-reviewed studies, this analysis showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice

scholarly journals Meta-analysis of neoadjuvant chemotherapy compared to radical cystectomy alone in improving overall survival of muscle-invasive bladder cancer patients

BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Agus Rizal A. H. Hamid ◽  
Fanny Riana Ridwan ◽  
Dyandra Parikesit ◽  
Fina Widia ◽  
Chaidir Arif Mochtar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Meta Analysis ◽  
Total Sample ◽  
Invasive Bladder Cancer ◽  
Forest Plot ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Abstract Background Most patients with muscle-invasive bladder cancer (MIBC) developed metastasis within 2 years, even after radical cystectomy (RC). The recurrence rate of MIBC was more than 50% of the cases. A meta-analysis conducted by Yin et al. showed that neoadjuvant chemotherapy (NAC) + RC improves overall survival in MIBC compared with RC only. However, a new meta-analysis by Li et al. concluded that NAC + RC was not superior to RC only in improving overall survival. The inconsistencies of these studies required further comprehensive analysis to recommend NAC use in bladder cancer treatment. Therefore, this meta-analysis aims to analyze previous studies that compare the efficacy of NAC + RC versus RC only to improve overall survival of MIBC. Methods The articles were searched using Pubmed with keywords “muscle-invasive bladder cancer”, “neoadjuvant chemotherapy”, “cystectomy”, and “overall survival”. The articles that were published until June 2020 were screened. The overall survival outcome was analyzed as hazard ratio (HR) and presented in a forest plot. Result Seventeen studies were included in meta-analysis with a total sample of 13,391 patients, consist of 2890 received NAC followed by RC and 10,418 underwent RC only. Two studies used methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), two studies used gemcitabine/cisplatin (GC), one study used Cisplatin-based regimen, one study used MVAC or GC, one study used gemcitabine/carboplatin (GCarbo) or GC or MVAC, one study used Cisplatin/Gemcitabine or MVAC, one study used Cisplatin only, one study used Cisplatin-based (GC, MVAC) or non-Cisplatin-based (combined paclitaxel/gemcitabine/carboplatin), one study used GC, MVAC, Carboplatin, or Gemcitabine/Nedaplatin (GN), and five studies did not mention the regimen The overall survival in the NAC + RC only group was significantly better than the RC only group (HR 0.82 [0.71–0.95], p = 0.009). Conclusion NAC + RC is recommended to improve overall survival in MIBC patients. A further study assessing side effects and quality of life regarding NAC + RC is needed to establish a strong recommendation regarding this therapy.

scholarly journals Evaluating the efficacy and safety of intravesical chemotherapies for non-muscle invasive bladder cancer: a network meta-analysis

Oncotarget ◽  
2016 ◽  
Vol 7 (50) ◽  
pp. 82567-82579 ◽  
Author(s):  
Chuanjun Zhuo ◽  
Xubin Li ◽  
Hongqing Zhuang ◽  
Shunli Tian ◽  
Hailong Cui ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Meta Analysis ◽  
Invasive Bladder Cancer ◽  
Efficacy And Safety ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Neoadjuvant Chemotherapy for Muscle‐Invasive Bladder Cancer: A Systematic Review and Two‐Step Meta‐Analysis

2016 ◽  
Vol 21 (6) ◽  
pp. 708-715 ◽  
Author(s):  
Ming Yin ◽  
Monika Joshi ◽  
Richard P. Meijer ◽  
Michael Glantz ◽  
Sheldon Holder ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Cisplatin-Based Neoadjuvant Chemotherapy for Elderly Patients with Muscle-Invasive Bladder Cancer: Is It Feasible?

2021 ◽  
Vol 5 (4) ◽  
pp. 1-1
Author(s):  
Clément Dumont ◽  
◽  
Madeleine Lefèvre ◽  
Quiterie Aussedat ◽  
Pierre-Louis Reignier ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Elderly Patients ◽  
Standard Of Care ◽  
Invasive Bladder Cancer ◽  
Hematological Toxicity ◽  
Routine Practice ◽  
Muscle Invasive Bladder Cancer ◽  
Increased Risk ◽  
Muscle Invasive

Cisplatin-based neoadjuvant chemotherapy (C-NAC) has been the standard of care in localized muscle-invasive bladder cancer (MIBC). However, the feasibility and benefit of C-NAC in elderly patients remain uncertain since this population has always been underrepresented in pivotal trials and is often barred from chemotherapy in routine practice because of their perceived frailty. Therefore, in order to evaluate the effectiveness of C-NAC in elderly patients with MIBS, we retrospectively reviewed the medical files of patients (cT2-4, N0-3, and M0) treated at our institution and aged 75 or older at the time of the first chemotherapy cycle. From May 2012 to March 2020, 51 patients aged 75 to 90 received C-NAC. Among them, 38 patients received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and 13 patients received gemcitabine and cisplatin (GC). In this study, the primary endpoint was the feasibility of C-NAC, evaluated as the percentage of patients who underwent at least four chemotherapy cycles. Overall feasibility of a complete four-cycle chemotherapy course was 75% (dose-dense MVAC [dd-MVAC]: 76%; GC: 69%). Incidence of grade 3-4 adverse events was 57%, mostly driven by hematological toxicity from dd-MVAC, and the incidence of febrile neutropenia was 6%. These results indicate the feasibility of C-NAC in elderly patients without any contraindication to cisplatin. A coordinated multidisciplinary approach, including a geriatric oncologist, may help to identify patients at increased risk for chemotherapy-induced toxicity, especially in patients aged 85 or older.

scholarly journals Perioperative pembrolizumab therapy in muscle-invasive bladder cancer: Phase III KEYNOTE-866 and KEYNOTE-905/EV-303

2021 ◽  
Author(s):  
Matthew D Galsky ◽  
Christopher J Hoimes ◽  
Andrea Necchi ◽  
Neal Shore ◽  
J Alfred Witjes ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Standard Of Care ◽  
Phase Iii ◽  
Invasive Bladder Cancer ◽  
Efficacy And Safety ◽  
Muscle Invasive Bladder Cancer ◽  
Clinical Trial Registration ◽  
Recent Phase ◽  
Muscle Invasive ◽  
Systemic Therapies

Muscle-invasive bladder cancer (MIBC) is associated with high rates of recurrence and poor prognosis despite aggressive treatment. Neoadjuvant chemotherapy before radical cystectomy (RC) improves outcomes in cisplatin-eligible patients; however, the improvement in overall survival is modest. Standard of care for cisplatin-ineligible patients remains RC; more effective systemic therapies are needed. Recent Phase Ib/II studies suggest pembrolizumab monotherapy and combination therapy are effective neoadjuvant therapies for MIBC. The randomized Phase III KEYNOTE-866 and KEYNOTE-905/EV-303 studies are being conducted to evaluate efficacy and safety of perioperative pembrolizumab or placebo with chemotherapy in cisplatin-eligible patients with MIBC (KEYNOTE-866) and of pembrolizumab monotherapy versus pembrolizumab plus enfortumab vedotin versus RC plus pelvic lymph node dissection alone in cisplatin-ineligible patients with MIBC (KEYNOTE-905/EV-303). Clinical trial registration: NCT03924856 & NCT03924895 (ClinicalTrials.gov)

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