Treatment of Metastatic Breast Cancer With Vinorelbine and Docetaxel

Savio, Giuseppina; Laudani, Agata; Leonardi, V.; Pepe, Alessio; Scianna, Caterina; Gebbia, Vittorio; Agostara, Biagio

doi:10.1097/01.coc.0000215456.56584.fc

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…The schedule variable also interacted with the ratio of docetaxel and vinorelbine, suggesting that the ratio was only important if the clinicians chose to intersperse single drug doses between treatments with the combination of drugs (test 8, Table IV). The results of the tests were similar when additional trials, mainly with paclitaxel substituted for docetaxel, were included in the dataset (57,(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77).…”

Section: Analysis Of Chemotherapy Clinical Trialsmentioning

confidence: 75%

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Uppal

Li²,

Wendt³

et al. 2007

Int J Oncol

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Abstract. Subcellular distribution of mass can be analyzed by a technique that involves culturing cells on interferometers and digitizing their interference contours. Contour sampling resulted in 102 variables per cell, which were predictors of oncogenic transformation. Cell phenotypes can be deconstructed by use of latent factors, which represent the covariance of the real variables. The reversal of the cancertype phenotype by a combination of microtubule-stabilizing and -depolymerizing agents was described previously. The implications of these results have been explored by clinicians who treated patients with the combination of docetaxel and vinorelbine (Navelbine ® ). The current study was performed to determine the effects of different combinations on phenotype and in phases of the cell cycle other than mitosis. Combinations of paclitaxel with either colchicine, podophyllotoxin, nocodazole, or vinblastine caused phenotype reversal. Paclitaxel analogue, 7-deoxytaxol, by itself caused reversal. Factors #4, (filopodia), #5 (displacement and/or deep invaginations in the periphery), #8, and #12 took on values typical of normal cells, whereas the values of #7 (p21-activated kinase), and #13 (rounding up) shifted toward the cancer-type. All combinations altered microtubule arrangement at the cell edge. Delivery schedules and drug ratios used in clinical studies were subjected to analysis. Clinical response rates were better when the combination was not interspersed with a single agent (P=0.004). The results support the idea that efficacy depends upon simultaneous exposure to both agents, and suggest a novel mechanism for combination therapies. These therapies appear to restore in transformed cells some of the features of a contactinhibited cell, and to impede progress through the cell cycle even when provided at nanomolar concentrations.

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Section: Analysis Of Chemotherapy Clinical Trialsmentioning

confidence: 75%

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Uppal

Li²,

Wendt³

et al. 2007

Int J Oncol

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“…An i.v. and oral formulations of VNR have been evaluated in combination with various cytotoxic agents in numerous studies for the treatment of metastatic breast cancer (Delozier et al , 2006; Sano et al , 2006; Savio et al , 2006). The drug has also proven efficacy and acceptable safety in association with trastuzumab (Burstein et al , 2001; Chan et al , 2006), overall response rates ranging from 44% to 86% (Chan, 2007).…”

mentioning

confidence: 99%

Phase I study of lapatinib plus vinorelbine in patients with locally advanced or metastatic breast cancer overexpressing HER2

et al. 2012

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Background:To determine the recommended doses of lapatinib (LPT) combined with vinorelbine (VNR) in women with human epidermal growth factor receptor 2-overexpressing advanced breast cancer pretreated with trastuzumab.Methods:In this phase I study, women were treated with oral daily LPT and i.v. VNR infused on days 1 and 8 every 3 weeks. Dose levels (DL) of LPT (mg)/VNR (mg m−2) ranged from 750/20 to 1250/30. The primary end point was feasibility based on maximal tolerated dose (MTD) and maximum administered dose (MAD). Pharmacokinetic interactions were investigated.Results:Of 33 patients included, 29 were evaluable. Two DLT occurred at DL4 (1000/25) meeting the MAD criteria. Despite an additional intermediate DL3′ (1250/22.5), MTD was reached at DL3 (1000/22.5). Grade 3–4 neutropenia was the most common toxicity (34% and 38% of patients, respectively). Other significant toxicities included grade 3–4 diarrhoea (3% each), and grade 3 asthenia (10%). Although not statistically significant, LPT (at 1000 or 1250 mg) decreased the VNR clearance by 30–40% compared with DL1.Conclusion:The MTD LPT 1000 mg/VNR 22.5 mg m−2 (DL3) is recommended for additional development. Pharmacokinetic interactions might increase the exposure to VNR and consequently alter the hematological tolerance.

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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: 69%

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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Treatment of Metastatic Breast Cancer With Vinorelbine and Docetaxel

Abstract: In patients with metastatic breast cancer previously treated with anthracyclines the combination vinorelbine-docetaxel is very active and well tolerated representing a valid therapeutic option for the management of this patient population.

Cited by 6 publications

References 27 publications

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Pattern analysis of microtubule-polymerizing and -depolymerizing agent combinations as cancer chemotherapies

Phase I study of lapatinib plus vinorelbine in patients with locally advanced or metastatic breast cancer overexpressing HER2

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

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