Clinical Data and Pharmacokinetics of a Docetaxel-vinorelbine Combination in Anthracycline Resistant/Relapsed Metastatic Breast Cancer

Airoldi, Mario; Cattel, Luigi; Pedani, Fulvia; Marchionatti, Sara; Tagini, Valentina; Bumma, C.; Recalenda, Valeria

doi:10.1080/02841860310010709

Cited by 12 publications

(7 citation statements)

References 13 publications

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“…Several recent reports from our group and others suggest that combinations of vinorelbine with paclitaxel or docetaxel are promising in patients with advanced lung, breast, and ovarian cancer (Kourousis et al 1998;Grunberg et al 1999;Ginopoulos et al 2002;Aravantinos et al 2003;Gomez-Bernal et al 2003). Temporal and sequencing effects of administration of vinorelbine and paclitaxel on drug efficacy and toxicity may also be important (Knick et al 1995;Budman et al 1996;Chang et al 1996;Sanchez et al 2002;Airoldi et al 2003). For example, in a P388 murine model, reduced toxicity of these agents is observed when they are administered simultaneously or within 6 h, whereas the same doses are lethal to animals when administered 24 h apart (Knick et al 1995).…”

Section: Discussionmentioning

confidence: 91%

Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549)

Jung

Grunberg

Timblin

et al. 2004

Histochemistry and Cell Biology

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Concurrent administration of paclitaxel and vinorelbine results in cytotoxicity in vivo and in vitro in a number of tumor cell lines, yet the mechanisms of enhanced cell killing are undefined. In studies here, we show that low concentrations (1 nM) of paclitaxel and vinorelbine in combination result in enhanced cell killing by apoptosis ( P<0.05) in the human lung adenocarcinoma cell line, A-549. In contrast, necrotic cell death and formation of multinucleated cells, which were significantly increased by paclitaxel ( P<0.05) alone, but not vinorelbine, were not increased synergistically by both drugs. Paclitaxel also caused microtubular disruption which was not observed with vinorelbine. These data provide further rationale for the combined use of paclitaxel and vinorelbine in clinical trials, and suggest that the cooperative effects of drugs on apoptosis are not mediated through similar disruptional effects on microtubules.

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Section: Discussionmentioning

confidence: 91%

Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549)

Jung

Grunberg

Timblin

et al. 2004

Histochemistry and Cell Biology

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“…To improve efficacy, research has focused on the freeze zone periphery and the use of agents to sensitize cells. Some studies have reported the synergistic effects of administering low‐dose 5‐fluorouracil, Taxotere®, or cisplatinum before cryotherapy, which results in improved cell ablation for the treatment of CaP in in vitro and in vivo models [18–26]. These studies have shown that sensitizing cell populations before freezing achieves enhanced cryoablative efficacy through the induction of apoptosis and secondary necrosis.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D₃ cryosensitization increases prostate cancer susceptibility to cryoablation via mitochondrial‐mediated apoptosis and necrosis

et al. 2011

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Objectives To investigate the effect and molecular mechanisms of action of Vitamin D3 (VD3) as a neo-adjunctive agent before cryosurgery in an effort to increase treatment efficacy for prostate cancer (CaP). To eliminate the potential for disease recurrence that exists at the periphery of the freeze lesion, where temperatures may be insufficient to destroy both androgen-sensitive (AS) and androgen-insensitive (AI) CaP. Methods Human CaP cells, LNCaP, were each genetically altered to express the AS and AI phenotypes and subjected to VD3 treatment and freezing in an in vitro and tissue-engineered model. Cell viability, caspase inhibitor and western blot studies were used to determine the basis of the different responses of AI and AS cells to VD3 cryosensitization. Results VD3 was found to be a highly effective cryosensitizer, resulting in a >50% overall increase in cell death after -15°C freezing. Fluorescence microscopy, western blot analysis and caspase protease assays confirmed that the increased activation of apoptosis was modulated through a mitochondrial-mediated pathway. Caspase inhibition studies showed that apoptosis played an integral role in cell death, with VD3 cryosensitivation-induced apoptotic events responsible for > 30% of the overall cell death after -15°C freezing. Conclusions The present study suggests that the use of VD3 as a cryosensitizer increases cryoablation efficacy through the increased activity of apoptosis as well as through necrosis. The data show that through VD3 treatment the overall level of AI CaP cell tolerance to freezing is reduced to a level similar to that of AS CaP. VD3 pre-treatment in conjunction with cryoablation may increase treatment efficacy and reduce disease recurrence for CaP patients.

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“…All disease sites responded to treatment, even if the small sample size precludes any firm conclusion about the relative occurrence of responses according to sites of disease. The median overall survival of 28.7 months is noteworthy, which is longer than that commonly reported with other regimens including docetaxel [4,11,12,13,21,22,23,24]. Treatment appeared to be slightly more active in previously anthracycline-‘exposed’ patients (response rate 50%) in comparison with ‘resistant’ patients (response rate 29%), even if the small sample size precludes any definite conclusion.…”

Section: Discussionmentioning

confidence: 72%

A Phase II Trial of Docetaxel and Vinorelbine in Patients with Advanced Breast Cancer Previously Treated with Anthracyclines

Vici¹,

Lauro²,

Sergi³

et al. 2008

Oncology

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Background: It was the aim of this study to evaluate the efficacy of docetaxel and vinorelbine combination in well-defined anthracycline-‘exposed’ or -‘resistant’ advanced breast cancer patients. Patients and Methods: A phase II trial was carried out enrolling 43 advanced breast cancer patients, all previously treated with anthracyclines, both in an adjuvant or advanced setting. Docetaxel 75 mg/m² as 1-hour infusion and vinorelbine 25 mg/m² as 30-min infusion were administered on day 1, every 3 weeks. Results: According to an intent-to-treat analysis, the response rate was 37.2% (95% CI 22.8–51.6) in 43 patients, whereas responses were observed in 16 (1 complete response, 15 partial response) out of 39 evaluable patients (41%, 95% CI 25.6–56.5); there were 50% with first-line and 33% with second-line therapy, and 50 and 29% of patients were considered anthracycline ‘exposed’ and ‘resistant’, respectively; responses by estrogen receptor (ER) status were given in 48% (ER positive) and 25% (ER negative), and by HER2 status, in 21% (HER2 positive) and 52% (HER2 negative). Median time to progression and median overall survival were 7.7 and 28.7 months, respectively. Toxicity was generally acceptable, with grade 3 neutropenia encountered in 15 (35%) patients and grade 4 neutropenia in 1 (2%) patient. Neutropenic fever occurred in 7 patients (16%), usually short-lasting. Grade 3 mucositis was encountered in 2 patients (5%). Conclusions: The combination of docetaxel and vinorelbine as a 3-weekly schedule is active and manageable in advanced breast cancer patients previously treated with anthracyclines.

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Clinical Data and Pharmacokinetics of a Docetaxel-vinorelbine Combination in Anthracycline Resistant/Relapsed Metastatic Breast Cancer

Cited by 12 publications

References 13 publications

Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549)

Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549)

Vitamin D₃ cryosensitization increases prostate cancer susceptibility to cryoablation via mitochondrial‐mediated apoptosis and necrosis

A Phase II Trial of Docetaxel and Vinorelbine in Patients with Advanced Breast Cancer Previously Treated with Anthracyclines

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Clinical Data and Pharmacokinetics of a Docetaxel-vinorelbine Combination in Anthracycline Resistant/Relapsed Metastatic Breast Cancer

Cited by 12 publications

References 13 publications

Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549)

Paclitaxel and vinorelbine cause synergistic increases in apoptosis but not in microtubular disruption in human lung adenocarcinoma cells (A-549)

Vitamin D3 cryosensitization increases prostate cancer susceptibility to cryoablation via mitochondrial‐mediated apoptosis and necrosis

A Phase II Trial of Docetaxel and Vinorelbine in Patients with Advanced Breast Cancer Previously Treated with Anthracyclines

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Vitamin D₃ cryosensitization increases prostate cancer susceptibility to cryoablation via mitochondrial‐mediated apoptosis and necrosis