Overall survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast cancer: A meta-analysis

Mauri, Davide; Kamposioras, Konstantinos; Tsali, Lampriani; Bristianou, Magdalini; Valachis, Antonis; Karathanasi, Ioanna; Georgiou, Christos D.; Polyzos, Nikolaos P.

doi:10.1016/j.ctrv.2009.10.006

Cited by 102 publications

(74 citation statements)

References 23 publications

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“…Several meta-analyses have found the weekly infusion schedule to be associated with lower toxicity. (17,18) In the case of liver dysfunction patients, we contend that a weekly docetaxel schedule further offers the benefit of minimising the risk of accidental over-dosing due to uncertainty in the dosing requirements of liver dysfunction patients. Overall, this dosing regimen appears to be well-tolerated in all three categories of patients at the given dosages.…”

Section: Discussionmentioning

confidence: 99%

Dose modifications in Asian cancer patients with hepatic dysfunction receiving weekly docetaxel: A prospective pharmacokinetic and safety study

et al. 2016

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Hepatic dysfunction may modify the safety profile and pharmacokinetics of docetaxel in cancer patients, but no validated guideline exists to guide dose modification necessitated by this uncommon comorbidity. We carried out the first prospective study of a personalized dosage regimen for cancer patients with liver dysfunction treated with docetaxel. Weekly dosages were stratified by hepatic dysfunction classification as such: Category 1, normal; Category 2, mild -alkaline phosphatase, aspartate aminotransferase, and ⁄ or alanine aminotransferase ≤53 upper limit of normal (ULN), and total bilirubin within normal range; and Category 3, moderate -any alkaline phosphatase, and aspartate aminotransferase or alanine aminotransferase ≤5-103 ULN, and ⁄ or total bilirubin ≤1-1.53 ULN. Category 1, 2 and 3 patients received starting dosages of 40, 30, and 20 mg ⁄ m 2 docetaxel, respectively. Pharmacokinetics were evaluated on day 1 and 8 of the first treatment cycle, and entered into a multilevel model to delineate interindividual and interoccasion variability. Adverse event evaluation was carried out weekly for two treatment cycles. We found that docetaxel clearance was significantly different between patient categories (P < 0.001). Median clearance was 22.8, 16.4, and 11.3 L ⁄ h ⁄ m 2 in Categories 1, 2, and 3, respectively, representing 28% and 50% reduced clearance in mild and moderate liver dysfunction patients, respectively. However, docetaxel exposure (area under the concentration-time curve) and docetaxel-induced neutropenia (nadir and the maximum percentage decrease in neutrophil count) were not significantly different between categories. Median area under the concentration-time curve was 1.74, 1.83, and 1.77 mgÁh ⁄ L in Categories 1, 2, and 3, respectively. The most common Grade 3 ⁄ 4 toxicity was neutropenia (30.0%). An unplanned comparison with the Child-Pugh and National Cancer Institute Organ Dysfunction Working Group grouping systems suggests that the proposed classification system appears to more effectively discriminate patients by docetaxel clearance and dose requirements. (ClinicalTrials.gov registration no. NCT00703378).H epatic dysfunction is a rare comorbidity affecting approximately 0.2% of cancer patients, (1) making it particularly challenging to accrue patients with hepatic dysfunction in oncology trials that assess its effects on the pharmacokinetics and safety profile of chemotherapeutic agents. The paucity of guidance on the treatment of this patient subpopulation can be a real practice issue in clinical oncology; many drugs that form the backbone of chemotherapy have narrow therapeutic windows and are often dosed close to maximally tolerable levels. Unacceptable toxicities can quickly set in if the implications of a reduced hepatic metabolic capacity are not properly regarded, as hepatic drug biotransformation is the predominant route of elimination for many cytotoxic agents.(2) We therefore propose that it may be helpful to risk-stratify cancer patients before starting them on a personalized d...

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Section: Discussionmentioning

confidence: 99%

Dose modifications in Asian cancer patients with hepatic dysfunction receiving weekly docetaxel: A prospective pharmacokinetic and safety study

et al. 2016

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“…This was previously demonstrated in our randomized phase III Prosty trial where triweekly and biweekly docetaxel dosing were compared in advanced castration-resistant prostate cancer (27). Weekly paclitaxel compared to triweekly infusions has also demonstrated survival benefit in advanced breast cancer (28).…”

Section: Patients (N=65)mentioning

confidence: 96%

Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer

Tiainen

Tanner

Lahdenperä

et al. 2016

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Abstract. Aim Metastatic breast cancer remains an incurable disease (1, 2). In Finland, nearly 5,000 patients are diagnosed with invasive breast cancer every year, and the incidence has increased steadily over the past decades. The Finnish cancer registry data from 2014 shows that 815 women died of metastatic breast cancer, which was the most common cause of cancer death in women (3). In the CONCORD-2 study, a central analysis of population-based registry data worldwide for cancer survival was conducted, and the results were published in The Lancet in November 2014. The study reported that the treatment results of breast cancer in Finland are among the best in the world. The 5-year-survival rate of patients with breast cancer in Finland was 86.8% [95% confidence interval (CI)=85.9-87.7%) from [2005][2006][2007][2008][2009], and was the highest in Northern Europe (4). However, new treatment options for advanced human epidermal growth factor receptor 2 (HER2)-negative disease are rare, and the overall survival benefit observed in these patients is modest (5, 6). For this reason, advanced HER2-negative breast cancer is a treatment challenge worldwide.Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial cell proliferation by blocking the binding of vascular endothelial growth factor A (VEGFA) to its receptor, therefore inhibiting tumor angiogenesis (7). Bevacizumab improves the outcomes of cytotoxic treatment in many metastatic malignancies, including colorectal, kidney, lung and ovarian cancer (8-11). There has been much debate about the status of bevacizumab treatment in metastatic breast cancer. Currently, the European Medicines Agency has only approved bevacizumab when combined with paclitaxel or capecitabine in a first or second-line setting (http://www.e ma.europa.eu/ema/). In 2011, the US Food and Drug Administration revoked its accelerated approval of a breast cancer indication for bevacizumab due to the lack of a benefit in breast cancer overall survival and, in addition, due to the potentially life-threatening side-effects (http://www.fda.gov/). 6431Τhis article is freely accessible online. In locally advanced and metastatic breast cancer, taxanebased treatment (docetaxel or paclitaxel), either in combination with another agent or as single-agent, therapy is considered one of the most effective choices for first-line treatment (5, 12), when cytotoxic treatment is needed. Combining bevacizumab with chemotherapy has been studied in certain phase III studies (13)(14)(15)(16)(17)(18). Most of these studies investigated the benefit of bevacizumab combined with a taxane. Furthermore, other chemotherapy regimens have been explored, including capecitabine, anthracycline, vinorelbine and gemcitabine. Adding bevacizumab has led to higher response rates and longer progression-free survival (PFS) throughout the trials, but no significant differences in overall survival (OS) have yet been observed.In addition to chemotherapy options, bevacizumab can also be combined with endocri...

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“…Docetaxel (D) has demonstrated significant activity, as a single agent or combined with other drugs, in several phase II and III clinical trials in the first-line setting, as well as in anthracycline-resistant MBC. There is no conclusive evidence that D mono-therapy given 3-weekly is more effective than the corresponding weekly regimen in MBC patients (1)(2)(3), although the superiority of the former was demonstrated in the adjuvant setting (4). Weekly D at a dose of 35-40 mg/m 2 induces a Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study response rate (RR) of 30-40% and leads to a time-to-progression (TTP) of 5-7 months (5), while 3-weekly D treatment is associated with an RR of 30-48% and a TTP of 4.2-6.5 months in phase II trials (6).…”

Section: Introductionmentioning

confidence: 92%

“…Weekly D at a dose of 35-40 mg/m 2 induces a Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study response rate (RR) of 30-40% and leads to a time-to-progression (TTP) of 5-7 months (5), while 3-weekly D treatment is associated with an RR of 30-48% and a TTP of 4.2-6.5 months in phase II trials (6). However, the weekly regimen seems to have a better toxicity profile causing less neutropenia, mucositis and neurotoxicity (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study

Pectasides

Papaxoinis²,

Kotoula³

et al. 2011

Oncol Rep

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Abstract.It is well known that low-dose metronomic chemotherapy has antiangiogenic activity. The aim of the present trial was to investigate the antiangiogenic properties of weekly docetaxel in patients with metastatic breast cancer. In total, 157 metastatic breast cancer patients received 35 mg/m 2 docetaxel weekly as a recommended treatment. Blood samples were collected before the start of chemotherapy (baseline) and during treatment. Nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A) plasma levels were measured at baseline and during treatment, while VEGF-A, endothelial nitric oxide synthase (eNOS) and thrombospondin-1 (THBS-1) peripheral blood mRNA levels were measured at baseline, in 127 patients and 39 female healthy controls. In general, the treatment was well-tolerated. Sixty-one patients (38%) achieved an objective response (4% complete and 34% partial response), while 52 (33%) had stable disease and 27 (17%) progressed. At a median follow-up of 33.5 months (range 2.8-45.0), 118 patients (74%) demonstrated disease progression and 94 (59%) had died.Median progression-free survival (PFS) was 8.8 months and median overall survival (OS) was 27.7 months. Median baseline level of plasma NO was significantly lower in patients than in healthy controls (p=0.010), while none of the plasma markers significantly changed upon docetaxel treatment. In addition, the median relative quantification value for THBS-1 mRNA was significantly higher (p<0.001) in patients as compared to healthy controls. NO plasma levels were positively associated with the number of organs involved (p=0.008). In multivariate analysis, low eNOS mRNA levels showed adverse prognostic significance for OS and high THBS-1 mRNA levels were found to be associated with shorter OS and PFS, independently from established clinical prognostic factors. Although an antiangiogenic activity of weekly docetaxel was not demonstrated in the present study, some interesting observations regarding the prognostic role of a number of blood angiogenic markers could be made.

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Overall survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast cancer: A meta-analysis

Cited by 102 publications

References 23 publications

Dose modifications in Asian cancer patients with hepatic dysfunction receiving weekly docetaxel: A prospective pharmacokinetic and safety study

Dose modifications in Asian cancer patients with hepatic dysfunction receiving weekly docetaxel: A prospective pharmacokinetic and safety study

Bevacizumab Combined with Docetaxel or Paclitaxel as First-line Treatment of HER2-negative Metastatic Breast Cancer

Expression of angiogenic markers in the peripheral blood of docetaxel-treated advanced breast cancer patients: A Hellenic Cooperative Oncology Group (HeCOG) study

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