Article

Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer

Eastern Cooperative Oncology Group, Philadelphia, USA.
New England Journal of Medicine (Impact Factor: 55.87). 04/2008; 358(16):1663-71. DOI: 10.1056/NEJMoa0707056
Source: PubMed

ABSTRACT

We compared the efficacy of two different taxanes, docetaxel and paclitaxel, given either weekly or every 3 weeks, in the adjuvant treatment of breast cancer.
We enrolled 4950 women with axillary lymph node-positive or high-risk, lymph node-negative breast cancer. After randomization, all patients first received 4 cycles of intravenous doxorubicin and cyclophosphamide at 3-week intervals and were then assigned to intravenous paclitaxel or docetaxel given at 3-week intervals for 4 cycles or at 1-week intervals for 12 cycles. The primary end point was disease-free survival.
As compared with patients receiving standard therapy (paclitaxel every 3 weeks), the odds ratio for disease-free survival was 1.27 among those receiving weekly paclitaxel (P=0.006), 1.23 among those receiving docetaxel every 3 weeks (P=0.02), and 1.09 among those receiving weekly docetaxel (P=0.29) (with an odds ratio >1 favoring the groups receiving experimental therapy). As compared with standard therapy, weekly paclitaxel was also associated with improved survival (odds ratio, 1.32; P=0.01). An exploratory analysis of a subgroup of patients whose tumors expressed no human epidermal growth factor receptor type 2 protein found similar improvements in disease-free and overall survival with weekly paclitaxel treatment, regardless of hormone-receptor expression. Grade 2, 3, or 4 neuropathy was more frequent with weekly paclitaxel than with paclitaxel every 3 weeks (27% vs. 20%).
Weekly paclitaxel after standard adjuvant chemotherapy with doxorubicin and cyclophosphamide improves disease-free and overall survival in women with breast cancer. (ClinicalTrials.gov number, NCT00004125 [ClinicalTrials.gov].).

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Available from: William C Wood, Mar 26, 2014
    • "Paclitaxel at a weekly schedule is less toxic compared to a three-weekly schedule [7]. Docetaxel is commonly administered every three weeks, but a weekly schedule might provide an effective and well tolerated alternative [6] [7]. http://dx.doi.org/10.1016/j.ctrv.2015.10.010 "
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    ABSTRACT: Background Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation of therapy, despite clinical response. Objective Pharmacogenetic studies were reviewed for identification of genetic variants possibly underlying individual susceptibility to adverse events. Method We conducted a systematic search in Pubmed and Embase for pharmacogenetic reports with focus on commonly reported taxane-related gastrointestinal, hematological and neurological toxicities in adult patients with solid tumors. The findings from a total of 51 eligible studies are presented in a comprehensive way. Results Most frequently investigated single nucleotide polymorphisms (SNPs) were located in genes encoding proteins affecting pharmacokinetics, such as drug transporters and genes of the cytochrome P450 family. Inconclusive data for risk of toxicity as well as for effects on drug exposure were reported on variants in ABCB1, CYP3A4, CYP3A5 and, for paclitaxel, CYP2C8. Interest is also dedicated towards genes involved in pharmacodynamics, such as detoxification of reactive oxygen species, DNA repair, neuronal processes and microtubule function. Recent studies include variants in TUBB2A, EPHA5 and EPHA6 for a possible association with neurotoxicity. Variations in methodological approach, sample size, study design, treatment schedule and end-point of toxicity affect consistency of results. Conclusion This review illustrates the complexity to well design pharmacogenetic studies for validation of SNPs that may clarify differences in taxane-induced toxicities among individuals. Novel genes encoding cellular targets of taxanes deserve further analysis by means of robust patient cohorts and definition of objective end-points.
    No preview · Article · Dec 2015 · Cancer Treatment Reviews
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    • "They concluded that the group receiving weekly paclitaxel had significantly more moderate-to-severe neuropathy than the group receiving standard therapy which was consistent with our results. Moreover, the group receiving docetaxel every 3 weeks showed significantly more severe neutropenia and its associated complications which were more frequent in docetaxel group than paclitaxel [5]. Ishikawa and colleagues evaluated the feasibility of AC/EC every three weeks followed by weekly paclitaxel or four cycles of three consecutive weekly administration followed by a one-week rest (3 × 4) and reported during AC/EC, (68%) of patients developed grade 3/4 granulocytopenia, compared to (7.8%) receiving 12 PAC and (2.1%) receiving 3 × 4 PAC. "
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    ABSTRACT: Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement in node-positive breast cancer patients but the optimal dose schedule has still remained undetermined. Objectives. The feasibility of dose-dense epirubicin in combination with cyclophosphamide (EC) followed by weekly paclitaxel as adjuvant chemotherapy in node-positive breast cancer patients was investigated. Methods. All patients were treated with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) every two weeks for four cycles with daily Pegfilgrastim (G-CSF) that was administered 3–10 days after each cycle of epirubicin and cyclophosphamide infusion which followed by (80 mg/m2) paclitaxel for twelve consecutive weeks. Results. Sixty consecutive patients were analyzed, of whom 57 patients (95%) completed the regimen and no case of toxicity-related death was observed. Grade 3/4 hematologic toxicity was uncommon and the most common grade 3/4 nonhematological adverse event was neuropathy disorders. Conclusions. Dose-dense epirubicin and cyclophosphamide followed by weekly paclitaxel with G-CSF support is a well-tolerated and feasible regimen in node-positive breast cancer patients without serious complications.
    Full-text · Article · Sep 2014
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    • "A patient who was treated with paclitaxel for angiosarcoma of the head and neck developed epiphora [12]. A phase III study comparing the efficacy of docetaxel and paclitaxel, given either weekly or every 3 weeks, in the adjuvant treatment of breast cancer showed that grade 3 and 4 tearing was reported in 5% of patients who received weekly docetaxel versus less than 1% of patients who received docetaxel once every 3 weeks, weekly paclitaxel, or paclitaxel once every 3 weeks [13]. The study also revealed that grade 2 tearing occurred 19%, 5%, 1% and 1%, respectively. "
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    ABSTRACT: Background Docetaxel is a key antineoplastic drug for treatment of non-small cell lung cancer. Ocular adverse events of docetaxel include epiphora (excess tearing) and conjunctivitis. Epiphora has been reported to be associated with canalicular and nasolacrimal duct stenosis, but it is not necessarily caused by lacrimal duct obstruction. Case presentation We encountered three Japanese non-small cell lung cancer patients who developed epiphora after the administration of docetaxel-based chemotherapy. One patient with lacrimal puncta stenosis showed improvement with probing and irrigation. The other two patients resolved following cessation of docetaxel or administration of artificial tears. Conclusion As epiphora can interfere with activities of daily life and negatively affect quality of life, it is important for thoracic oncologists to be aware of this adverse event.
    Full-text · Article · May 2014 · BMC Research Notes
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