Re-Challenging Taxanes in Recurrent Breast Cancer in Patients Treated with (Neo-)Adjuvant Taxane-Based Therapy

German Breast GroupUniversitäts-Frauenklinik Frankfurt, Saarbrücken, Deutschland.
Breast Care (Impact Factor: 0.63). 08/2011; 6(4):279-283. DOI: 10.1159/000330946
Source: PubMed


Background: Docetaxel and paclitaxel are among the most active substances for the treatment of breast cancer. As both drugs are used today in adjuvant regimens, efficacy data from pivotal trials in the metastatic setting in taxane-naive populations cannot reliably be used as references. Patients and Methods: The Taxane Re-Challenge Cohort Study identified participants from 6 prospective (neo-)adjuvant taxane-based studies with recurrent disease and collected data on their subsequent treatment. Out of 381 recurrent patients, 106 (27.8%) were re-challenged with a taxane-based treatment as first- or later-line therapy for recurrent disease. Results: Taxanes were used as first-line therapy in 74 patients and showed a response rate of 48.6% (including complete responses in 27.0%). The response rate was dependent on the disease-free interval (<1 year: 34.8%; 1-2 years: 42.9%; >2 years: 63.3%; p = 0.04) and visceral metastasis (present: 62.5%; not present 32.4%; p = 0.01). Patients without visceral metastasis and with a disease-free interval of >2 years achieved the longest overall survival. Hormone and HER2 receptor status were not predictive; however, triple-negative tumors responded in 50.0%. The overall response rate of later-line taxane-based treatment was 28.2%. Conclusion: Re-challenging taxanes appears to be effective and therefore represents a reasonable option in this population.

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Available from: Volker Jochen Möbus, Jul 11, 2014
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    • "An analysis of our data showed that this doublet is effective in patients pretreated with taxanes. As reported by Guo et al, rechallenging taxane as first- and later-line treatment for patients with recurrent disease after (neo-)adjuvant taxane-based therapy yielded response rates of 48.6% and 28.2%, respectively, which was considered by the authors as a reasonable option.33 In our study, more than half of the patients (58.9%) had been pretreated with taxanes, among whom 12 patients (16.4%) were exposed to taxanes in the metastatic setting. "
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    ABSTRACT: Although nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is approved to be given every 3 weeks, weekly use of this drug is becoming a new standard of care in patients with metastatic breast cancer (MBC). This prospective Phase II study was conducted to improve the efficacy of weekly nab-paclitaxel with cisplatin in MBC patients. Seventy-three women with recurrent or MBC were eligible for participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m(2) on day 1, day 8, and day 15, followed by cisplatin 75 mg/m(2) on day 1, repeated every 28 days with a maximum of 6 cycles. The primary objective was investigator-assessed overall response rate (ORR). A high ORR of 67.1% was obtained, with rates of 80.6% for the first-line patients and 80% for patients not pretreated with taxanes. Among those who had objective responses, a large percentage of patients (83.7%) showed quickly remarkable tumor shrinkage during the first two cycles. The median progression-free and overall survival times were 9.8 and 26.9 months, respectively. For the patients receiving first-, second-, and third-line therapy or beyond, median progression-free survival was 11.7, 7.7, and 7.6 months, respectively (P=0.005). Molecular subtype was not significantly associated with ORR or disease progression. Grade 4 neutropenia occurred in 46 patients (63.0%), with febrile neutropenia found in 9 patients (12.3%). Grade 3 peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19 patients (26.0%). Efficacy of weekly nab-paclitaxel can be improved by adding cisplatin. The doublet is highly effective, with quick response, manageable toxicity, and possible equivalence across molecular subtypes in MBC patients.
    International Journal of Nanomedicine 03/2014; 9(1):1443-52. DOI:10.2147/IJN.S58275 · 4.38 Impact Factor
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    • "Many of the studies described above defined patients with prior exposure to a taxane in the metastatic setting and not exclusively the neoadjuvant or adjuvant setting. A recent study out of Germany called the Taxane Re-Challenge Cohort Study retrospectively identified 381 patients with recurrent disease who were treated in the neoadjuvant or adjuvant setting with a taxane-based regimen.78 Data were collected on their subsequent treatment. "
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    ABSTRACT: Taxanes have remained a cornerstone of breast cancer treatment over the past three decades, improving the lives of patients with both early- and late-stage disease. The purpose of this review is to summarize the current role of taxanes, including an albumin-bound formulation that enhances delivery of paclitaxel to tumors, in the management of metastatic breast cancer (MBC). Since the introduction of Cremophor EL-paclitaxel to the clinic in the mid-1990s, a substantial amount of investigation has gone into subjects such as formulation, dose, schedule, and taxane resistance, allowing physicians greater flexibility in treating patients with MBC. This review will also examine how the shrinking pool of taxane-naive patients, a result of the expansion of taxanes into the neoadjuvant and adjuvant settings, will respond to taxane retreatment for metastatic disease. Taxane treatment seems likely to continue to play an important role in the treatment of MBC.
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    ABSTRACT: Anthracyclines and taxanes are cytotoxic agents that are commonly used for the treatment of breast cancer, including in the adjuvant, neoadjuvant, and metastatic setting. Each drug class of is associated with cumulative and potentially irreversible toxicity, including cardiomyopathy (anthracyclines) and neuropathy (taxanes). This may either limit the duration of therapy for advanced disease, or prevent retreatment for recurrence if previously used as component of adjuvant or neoadjuvant therapy. Several classes of cytotoxic agents have been evaluated in patients with anthracycline and taxane-pretreated metastatic breast cancer (MBC), including other antitubulins (vinorelbine, ixabepilone, eribulin), antimetabolites (capecitabine, gemcitabine), topoisomerase I inhibitors (irinotecan), platinum analogues (cisplatin, carboplatin), and liposomal doxorubicin preparations. No trials have shown an overall survival advantage for combination chemotherapy in this setting, indicating that single cytotoxic agents should usually be used, expect perhaps in patients with rapidly progressive disease and/or high tumor burden.
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