Single-Agent Gemcitabine vs. Carboplatin-Gemcitabine in Advanced Breast Cancer: A Retrospective Comparison of Efficacy and Safety Profiles

Vernieri, Claudio; Prisciandaro, Michele; Milano, Monica; Cona, Maria Silvia; Maggi, Claudia; Brambilla, Marta; Mennitto, Alessia; Fabbroni, Chiara; Farè, Elena; Cresta, Sara; Celio, Luigi; Mariani, Gabriella; Bianchi, Giulia; Capri, Giuseppe; Braud, Filippo de

doi:10.1016/j.clbc.2018.12.004

Cited by 15 publications

(18 citation statements)

References 37 publications

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“…In a recently published monocentric study comparing combination carboplatin-gemcitabine (CG) with single-agent gemcitabine (G) in mBC patients, we found that CG was associated with longer OS despite the lack of significant PFS differences [24]. However, the high clinical heterogeneity between CG-and G-treated patients, and in particular the fact that patients receiving CG were less heavily pre-treated, provides a reasonable and simplistic explanation to results of our prior analysis.…”

Section: Discussionmentioning

confidence: 55%

“…Non-hematologic toxicities were extracted from medical records, where they are regularly annotated during patient visits. Since the grading of patient symptoms in retrospective studies may be not fully reliable, mainly due to the AE under-reporting or under-grading, in this study non-hematologic AEs were reported as any-grade AEs, as previously described [24].…”

Section: Assessment Of Efficacy and Safetymentioning

confidence: 99%

“…We used a higher threshold for determining statistical significance at univariate analysis because we wanted to be less stringent in the selection of covariates that were then tested in the multivariable Cox model. All statistical analyses were performed using the software R (version 3.3.2 (2016-10-31)) [24].…”

Section: Statistical Analysesmentioning

confidence: 99%

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Oral Capecitabine-Vinorelbine Is Associated with Longer Overall Survival When Compared to Single-Agent Capecitabine in Patients with Hormone Receptor-Positive Advanced Breast Cancer

Vernieri

Prisciandaro

Nichetti

et al. 2020

Cancers

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Background: Single-agent capecitabine (C) is a moderately effective chemotherapeutic compound in the treatment of patients with HER2-negative metastatic breast cancer (mBC). The capecitabine-vinorelbine (CV) combination is also used due to a good tolerability profile, but no studies have demonstrated its superiority over single-agent C. Methods: We conducted a retrospective analysis to compare overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and incidence of adverse events (AEs) in patients with HER2-negative mBC treated with CV vs. single-agent C. Results: Out of 290 patients included in this study, 127 (43.8%) received single-agent C, while 163 (56.2%) patients were treated with CV. Median PFS was similar in patients treated with single-agent C or CV, while CV was associated with significantly longer OS in patients with hormone receptor-positive (HR+) BC. This OS advantage was confirmed at multivariable analysis also after propensity score-based matching of patients according to relevant clinical or tumor characteristics. When compared with single-agent C, CV was associated with higher incidence of G3/G4 and any-grade nausea/vomiting, diarrhea and increased transaminases. Conclusions: While prospective studies are Cancers 2020, 12, 617 2 of 15 needed to confirm our findings, the potential OS advantage of CV over single-agent C in HR+ mBC patients must be weighed against a significantly higher incidence of AEs.

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Section: Discussionmentioning

confidence: 55%

Section: Assessment Of Efficacy and Safetymentioning

confidence: 99%

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Oral Capecitabine-Vinorelbine Is Associated with Longer Overall Survival When Compared to Single-Agent Capecitabine in Patients with Hormone Receptor-Positive Advanced Breast Cancer

Vernieri

Prisciandaro

Nichetti

et al. 2020

Cancers

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“…In this study, we found that grade 3 or higher hematological toxicities occurred more frequently in gemcitabine‐oxaliplatin doublets than in gemcitabine alone (34.09% vs 9.09%; P = .035). Vernieri et al also found that patients receiving gemcitabine‐carboplatin combination chemotherapy had a significantly higher incidence of G3‐G4 neutropenia than those receiving gemcitabine alone (24% vs 6.6%; P < .0001) 23 . Therefore, age, BSA, sex, ECOG, and chemotherapy scheme were used as adjustment factors for association analysis of genotype and hematological toxicity.…”

Section: Discussionmentioning

confidence: 99%

Gene‐Gene Interactions of Gemcitabine Metabolizing‐Enzyme Genes hCNT3 and WEE1 for Preventing Severe Gemcitabine‐Induced Hematological Toxicity

Chen

et al. 2021

The Journal of Clinical Pharma

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Most patients experience severe hematological toxicity during treatment with gemcitabine; thus, preventing such toxicity would improve the treatment effects and patient quality of life. We analyzed 13 polymorphisms in the transporters, metabolizing enzymes, targets, and genes involved in DNA damage and the folate pathway among 132 patients treated with gemcitabine and studied their association with the severity of the hematological toxicities. Single‐locus analysis showed that the single‐nucleotide polymorphisms (SNPs) RRM1 rs12806698 and rs11031918 and DCTD rs7663494 were significantly associated with severe neutropenia, hENT1 rs760370 and hCNT3 rs7867504 and rs4877831 were associated with severe leukopenia, CDA rs2072671, DCTD rs7663494, and WEE1 rs3910384 were associated with severe anemia, and MTHFR rs1801133 was associated with severe thrombocytopenia after stringent Bonferroni correction (P < .0038). The gene‐gene interaction analysis identified the overall best models, including a 2‐way interaction model (hCNT3 rs7867504 and dCK rs12648166) for severe leukopenia (P = .0022) and a 3‐locus model (CDA rs207671, DCTD rs7663494, and WEE1 rs3910384) for severe anemia with a strong synergistic effect (P = .0001). The association with hematological toxicity was further strengthened by the results of a haplotype analysis, in which the homozygous genotype combination of rs3910384 CC, rs2072671 AA, rs12648166 GG, rs7867504 CC, and rs7663494 TT conferred high genetic susceptibility to severe thrombocytopenia. Our results suggest that the gene‐gene interaction of gemcitabine metabolic pathway genes and WEE1 contributes to susceptibility to gemcitabine‐induced hematological toxicity. Moreover, we propose a promising data‐mining analysis approach (generalized multifactor dimensionality reduction) to detect and characterize gene‐gene interactions.

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“…To arise the efficacy of treating bladder cancer or muscle invasive bladder cancer gemcitabine is combined with platinum 14 , 15 . To increase the efficacy of treating advanced breast cancer gemcitabine is combined with carboplatin 16 . To improve the efficacy of treating germ cell cancer, as well as metastatic and unresectable transitional cell carcinoma gemcitabine is combined with sorafenib 17 , 18 .…”

Section: Introductionmentioning

confidence: 99%

Exploring the action of RGDV-gemcitabine on tumor metastasis, tumor growth and possible action pathway

Zhang

et al. 2020

Sci Rep

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The coupling of Arg-Gly-Asp-Val (RGDV) and gemcitabine led to a hypothesis that the conjugate (RGDV-gemcitabine) could inhibit tumor metastasis. To confirm this hypothesis the activities of RGDV-gemcitabine inhibiting tumor metastasis in vitro and in vivo were presented for the first time. AFM (atomic force microscopy) imaged that RGDV-gemcitabine was able to adhere onto the surface of serum-starved A549 cells, to block the extending of the pseudopodia. Thereby RGDV-gemcitabine was able to inhibit the invasion, migration and adhesion of serum-starved A549 cells in vitro. On C57BL/6 mouse model RGDV-gemcitabine dose dependently inhibited the metastasis of planted tumor towards the lung and the minimal dose was 0.084 µmol/kg/3 days. The decrease of serum TNF-α (tumor necrosis factor), IL-8 (interleukin-8), MMP-2 (matrix metalloprotein-2) and MMP-9 (matrix metalloprotein-9) of the treated C57BL/6 mice was correlated with the action pathway of RGDV-gemcitabine inhibiting the metastasis of the planted tumor towards lung.

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Single-Agent Gemcitabine vs. Carboplatin-Gemcitabine in Advanced Breast Cancer: A Retrospective Comparison of Efficacy and Safety Profiles

Cited by 15 publications

References 37 publications

Oral Capecitabine-Vinorelbine Is Associated with Longer Overall Survival When Compared to Single-Agent Capecitabine in Patients with Hormone Receptor-Positive Advanced Breast Cancer

Oral Capecitabine-Vinorelbine Is Associated with Longer Overall Survival When Compared to Single-Agent Capecitabine in Patients with Hormone Receptor-Positive Advanced Breast Cancer

Gene‐Gene Interactions of Gemcitabine Metabolizing‐Enzyme Genes hCNT3 and WEE1 for Preventing Severe Gemcitabine‐Induced Hematological Toxicity

Exploring the action of RGDV-gemcitabine on tumor metastasis, tumor growth and possible action pathway

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