Phase II study of vinorelbine with low dose prednisone in the treatment of hormone-refractory metastatic prostate cancer

Robles, Carlos; Fürst, A; Sriratana, P.; Lai, Sue Min; Chua, Li; Donnelly, E.; Solomon, Jeanine; Sundaram, Murali; Feun, Lynn G.; Savaraj, Niramol

doi:10.3892/or.10.4.885

Cited by 4 publications

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“…In a retrospective evaluation of oral dexamethasone regimen in 99 patients, 40.4% of PSA response was found [124]. Intravenous vinorelbine 25 mg/m 2 weekly for first 12 weeks and biweekly afterwards was used with low dose oral prednisone in 14 patients, with a PSA response in 29% [125]. Oral metronomic vinorelbine was also evaluated with serum markers of tumor response and activity.…”

Section: Resultsmentioning

confidence: 99%

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

Şimşek

Esin

Yalçın

2019

Journal of Oncology

102

100

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Metronomic chemotherapy, continuous and dose-dense administration of chemotherapeutic drugs with lowered doses, is being evaluated for substituting, augmenting, or appending conventional maximum tolerated dose regimens, with preclinical and clinical studies for the past few decades. To date, the principle mechanisms of its action include impeding tumoral angiogenesis and modulation of hosts’ immune system, affecting directly tumor cells, their progenitors, and neighboring stromal cells. Its better toxicity profile, lower cost, and easier use are main advantages over conventional therapies. The evidence of metronomic chemotherapy for personalized medicine is growing, starting with unfit elderly patients and also for palliative treatment. The literature reviewed in this article mainly demonstrates that metronomic chemotherapy is advantageous for selected patients and for certain types of malignancies, which make it a promising therapeutic approach for filling in the gaps. More clinical studies are needed to establish a solidified role for metronomic chemotherapy with other treatment models in modern cancer management.

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Section: Resultsmentioning

confidence: 99%

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

Şimşek

Esin

Yalçın

2019

Journal of Oncology

102

100

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“…It improves the effects of the various drugs used in CRPC treatment. Studies have reported that vinblastine improves the function of docetaxel and prednisone in treating CRPC ( 8 , 18 , 19 ). Moreover, vinblastine treatment of PCa and CRPC has also been reported in vitro .…”

Section: Discussionmentioning

confidence: 99%

CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine

Chen

Wang

et al. 2022

Front. Endocrinol.

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BackgroundProstate cancer (PCa) is a common malignancy occurring in men. As both an endocrine and gonadal organ, prostate is closely correlated with androgen. So, androgen deprivation therapy (ADT) is effective for treating PCa. However, patients will develop castration-resistant prostate cancer (CRPC) stage after ADT. Many other treatments for CRPC exist, including chemotherapy. Vinblastine, a chemotherapeutic drug, is used to treat CRPC. However, patients will develop resistance to vinblastine. Genetic alterations have been speculated to play a critical role in CRPC resistance to vinblastine; however, its mechanism remains unclear.MethodsVarious databases, such as Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Chinese Prostate Cancer Genome and Epigenome Atlas (CPGEA), were used to collect the RNA-sequence data of PCa and CRPC patients and vinblastine-resistant PCa cells. Using online tools, Metascape and TIMER, the pathways and immune infiltration associated with vinblastine resistance-related genes in PCa were analyzed. The function of these genes was verified in clinical samples and CRPC cells.ResultsUsing GSE81277 dataset, we collected the RNA-sequence data of vinblastine sensitive and resistant LNCaP cells and found nine genes (CDC20, LRRFIP1, CCNB1, GPSM2, AURKA, EBLN2, CCDC150, CENPA and TROAP) that correlated with vinblastine resistance. Furthermore, CCNB1, GPSM2 and AURKA were differently expressed between normal prostate and PCa tissues, even influencing PCa progression. The GSE35988 dataset revealed that CCNB1 and AURKA were upregulated in PCa and CRPC samples. Various genes were also found to affect the survival status of PCa patients based on TCGA. These genes were also related to immune cell infiltration. Finally, we verified the function of CCNB1 and AURKA and observed that they were upregulated in PCa and CRPC clinical samples and increased the sensitivity of CRPC cells to vinblastine.ConclusionCCNB1 and AURKA are central to CRPC resistance to vinblastine and affect PCa progression.

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Hoosier Oncology Group Randomized Phase II Study of Docetaxel, Vinorelbine, and Estramustine in Combination in Hormone-Refractory Prostate Cancer with Pharmacogenetic Survival Analysis

Hahn¹,

Marsh

Fisher

et al. 2006

Clinical Cancer Research

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Purpose: To determine the safety and efficacy of two docetaxel doublets in hormone-refractory prostate cancer (HRPC) patients and to examine the prognostic role of polymorphisms in host genes important to docetaxel metabolism and transport. Experimental Design: Sixty-four chemotherapy-naive patients with HRPC were randomized to docetaxel and vinorelbine (D, 20 mg/m 2 i.v. days 1 and 8; V, 25 mg/m 2 i.v. days 1 and 8) or docetaxel and estramustine phosphate (D, 60-70 mg/m 2 i.v. day 1; E, 280 mg oral thrice daily days 1-5) administered q21d. Primary end point was clinically significant toxicity. A pharmacogenetic analysis of host genes was done in patients who received at least one cycle of docetaxel therapy. Results: Grade 3/4 toxicity occurred in 15.6% of DV patients and in 28.6% DE patients. Neither arm exceeded the threshold of clinically significant toxicity. In the DV arm, objective response rate was 33%, prostate-specific antigen response rate was 20%, and median survival was 16.2 months. In the DE arm, objective response rate was 67%, prostate-specific antigen response rate was 43%, and median survival was 19.7 months. Pharmacogenetic analyses showed a significant association between survival beyond 15 months and the ABCG2 421C>A (Q141K) polymorphism compared with the wild-type (C/C) genotype (66% versus 27%; P = 0.05). Conclusions: DV and DE doublets are active with a tolerable toxicity profile in patients with HRPC; however, efficacy does not seem superior to standard single-agent docetaxel.The ABCG2 421C>A (Q141K) polymorphism may be an important predictor of response and survival in HRPC patients treated with docetaxel-based chemotherapy.Prostate cancer afflicts 234,000 men yearly and results in >27,000 deaths (1). Recent trials have shown a survival benefit for men with hormone-refractory prostate cancer (HRPC) treated with a docetaxel-based regimen (2, 3).Vinorelbine is a Vinca alkaloid that inhibits the microtubular apparatus in malignant cells and has documented activity in HRPC (4-6). Vinorelbine and docetaxel inhibit different portions of the microtubule apparatus in a synergistic manner in preclinical in vitro prostate cancer models (7-9). With this in mind, the Hoosier Oncology Group conducted a randomized phase II trial of weekly docetaxel and vinorelbine (DV) with docetaxel and estramustine phosphate (DE) as a parallel reference arm.This study also included a pharmacogenetic analysis of host genes with critical roles in docetaxel drug transport and metabolism. Clinical studies suggest that variant alleles in the thiopurine methyltransferase gene can identify patients at risk of severe hematologic toxicity after azathioprine, 6-mercaptopurine, or related agents (10). Similar toxicity associations are seen with dihydropyrimidine dehydrogenase gene mutations and 5-fluorouracil therapy (11) and with UGT1A1 mutations and irinotecan (12). Single-nucleotide polymorphisms (and other genetic variants) have also been observed, which affect docetaxel metabolism and transport. These include alt...

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Phase II study of vinorelbine with low dose prednisone in the treatment of hormone-refractory metastatic prostate cancer

Cited by 4 publications

References 0 publications

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

CCNB1 and AURKA are critical genes for prostate cancer progression and castration-resistant prostate cancer resistant to vinblastine

Hoosier Oncology Group Randomized Phase II Study of Docetaxel, Vinorelbine, and Estramustine in Combination in Hormone-Refractory Prostate Cancer with Pharmacogenetic Survival Analysis

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