Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?

Pouessel, Damien; Chevret, Sylvie; Rolland, Frédéric; Gravis, Gwénaëlle; Geoffrois, L.; Roubaud, Guilhem; Terrisse, Safae; Boyle, Helen; Chevreau, Christine; Dauba, Jérôme; Moriceau, Guillaume; Alexandre, Ingrid; Deplanque, Gaël; Chapelle, Angélique; Vauléon, Élodie; Colau, A.; Audenet, François; Grellety, Thomas; Culine, Stéphane

doi:10.1016/j.ejca.2015.11.017

Cited by 12 publications

(8 citation statements)

References 17 publications

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“…An initial meta-analysis of clinical trials comparing MVAC and GC did show a reduced OS with GC (HR 1.26); however, when carboplatin, which is no longer recommended as a chemotherapy agent, was excluded, the difference was not statistically significant [30]. In addition, both dose-dense MVAC (ddMVAC) [31,32] and accelerated MVAC (aMVAC) [33,34] have been studied with similar outcomes and acceptable toxicity in comparison to traditional MVAC. In a recent study by Peyton et al comparing ddMVAC to GC, there was a higher likelihood of downstaging and complete response with patients who received ddMVAC (pT0N0 41.3% vs. 24.5%) with a nonsignificant trend towards improved OS (HR 0.44, p = 0.16) [35].…”

Section: Factors Affecting Likelihood Of Pt0mentioning

confidence: 99%

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

Tse

Ghandour

Singla

et al. 2019

IJMS

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Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (ATM, RB1, FANCC, ERCC2, BRCA1, and ERCC1), regulators of apoptosis (survivin, Bcl-xL, and emmprin), receptor tyrosine kinases (EGFR and erbB2), genes involved in cellular efflux (MDR1 and CTR1), in addition to molecular subtypes (Basal, luminal, and p53-like). The current state of the literature on the prediction of response to NAC based on the presence of these biomarkers is discussed in this review.

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Section: Factors Affecting Likelihood Of Pt0mentioning

confidence: 99%

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

Tse

Ghandour

Singla

et al. 2019

IJMS

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“…After assessing the full texts of these potentially relevant studies, 284 were excluded for the following reasons: 189 were researches on radiation therapy, 85 were completely not associated with dose-dense chemotherapy, 5 were about adjuvant therapy, 4 contained no relative outcomes, and 1 was with a too small sample size. Ultimately, 10 eligible articles [ 7 , 9 – 17 ] involving a total of 1093 patients were included for analyses. No additional unpublished trials were added to the literature search results.…”

Section: Resultsmentioning

confidence: 99%

“…Results of the literature search identified 10 eligible papers. Among those papers, three [ 7 , 9 , 16 ] were controlled trials comparing dd-MVAC with classic MVAC, one [ 17 ] was another controlled trial comparing a dd-GC (gemcitabine 2500 mg/m2 and cisplatin 70 mg/m2, q 2 weeks) regimen with dd-MVAC which suggested that although not superior to dd-MVAC, dd-GC was better tolerated, and one [ 11 ] was AG-TC which was doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin. The rest were single-arm trials exploring the safety and/or the activity of dd-MVAC regimen.…”

Section: Resultsmentioning

confidence: 99%

“…The risk of bias and quality assessments of the included studies are outlined in Figure 7A, 7B . The Jadad score of two controlled trials [ 7 , 16 ] were 3 and one [ 9 ] got a score of 2. Overall, the quality of the included studies was satisfactory.…”

Section: Resultsmentioning

confidence: 99%

“…In 1993, the classic MVAC regimen was modified into dose-dense MVAC (dd-MVAC) which was administered in cycles of 14 days. Dd-MVAC was shown to have fewer dose delays and a more favorable toxicity profile than classic MVAC group [ 8 ] in a randomized phase III trial, however in another study [ 9 ], similar pathological responses were observed between the two groups.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma

et al. 2017

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We conducted a meta-analysis to assess the efficacy and safety of dose-dense chemotherapy in the treatment of patients with urothelial carcinoma. A systematic search was conducted in PubMed, Medline, Embase, Web of Science and Cochrane Collaboration's Central register of controlled trials (CENTRAL) for relevant articles. Data was obtained from 10 trials with a total of 1093 patients. The pooled pathologic complete response (pCR) was 27.8% in the ten studies with a full cohort of 684 patients who received dose-dense methotrexate, vinblastine, adriamycin and cisplatin (dd-MVAC). In the controlled trials, although the difference was not significant, the pCR rate in the dd-MVAC group has a trend of increase (odds ratio (OR) 1.52; 95% confidence interval (CI) 0.78-2.98, P = 0.22) compared with classic MVAC group. A significant improvement of overall survival (OS) (hazard ratio (HR) 0.77, 95% CI 0.61–0.97, p = 0.03) was also observed. Hematologic toxicities were the most frequent grade ≥ 3 toxicities including neutropenia/febrile neutropenia (17.5%), anemia (9.4%) and thrombocytopenia (6.1%). Compared with the classic MVAC group, dd-MVAC was associated with significantly decreased risks of all-grade adverse events (AEs) such as anemia (OR 0.457, 95% CI 0.249–0.840, p = 0.012), febrile neutropenia (OR 0.398 95% CI 0.233–0.681, p = 0.001), and neutropenia (OR 0.373, 95% CI 0.201–0.691, p = 0.002). In conclusion, dose-dense chemotherapy was effective and tolerable in patients with urothelial carcinoma, which could be considered as a reasonable therapeutic option.

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Correlations of CTLA‐4 exon‐1 49 A/G and promoter region 318C/T polymorphisms with the therapeutic efficacy of ¹³¹I radionuclide in graves’ disease in Chinese Han population

Han

Wen

Wang

et al. 2018

J of Cellular Biochemistry

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Graves' disease is an autoimmune process in which the thyroid gland is triggered by autoantibodies, resulting in hyperthyroidism. The purpose of the present study is to elucidate whether exon-1 49 A/G and promoter region 318C/T polymorphisms in the CTLA-4 gene. This study consisted of 653 eligible patients with Graves' disease. After receiving 131I radionuclide therapy, these patients were classified into the remission and non-remission groups. A logistic regression-based model was used to analyze independent factors affecting the patient response to 131I radionuclide therapy. The results showed that CTLA-4 49 A/G was closely related to the efficacy of I treatment for Graves' disease (AG + GG vs. AA: OR = 6.543, 95%CI = 2.611 ∼ 16.40, P< 0.001; G vs. A: OR = 3.482, 95%CI = 2.457 ∼ 4.934, P < 0.001). Moreover, the findings revealed that haplotype A-C (P < 0.001, OR = 3.592, 95%CI: 2.451 ∼ 5.262) and G-C (P < 0.001, OR = 0.282, 95%CI: 0.204 ∼ 0.391) were associated with the efficacy of I therapy in treating Graves' disease. Logistic regression analysis indicated that thyroid weight (OR = 0.963, 95%CI = 0.944 ∼ 0.982, P< 0.001) and CTLA-4 exon-1 49 A/G polymorphism (OR = 0.334, 95%CI = 0.233 ∼ 0.478, P < 0.001) independently affect the efficacy of I therapy in Graves' disease. These data indicated that CTLA-4 exon-1 49 A/G polymorphism may be associated with patient response to radionuclide I therapy in Graves' disease.

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Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?

Cited by 12 publications

References 17 publications

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma

Correlations of CTLA‐4 exon‐1 49 A/G and promoter region 318C/T polymorphisms with the therapeutic efficacy of ¹³¹I radionuclide in graves’ disease in Chinese Han population

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Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?

Cited by 12 publications

References 17 publications

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts

Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma

Correlations of CTLA‐4 exon‐1 49 A/G and promoter region 318C/T polymorphisms with the therapeutic efficacy of 131I radionuclide in graves’ disease in Chinese Han population

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Product

Resources

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Correlations of CTLA‐4 exon‐1 49 A/G and promoter region 318C/T polymorphisms with the therapeutic efficacy of ¹³¹I radionuclide in graves’ disease in Chinese Han population