A multicenter randomized study comparing vinorelbine plus gemcitabine versus capecitabine monotherapy as salvage treatment in patients with advanced breast cancer pretreated with taxane and anthracycline chemotherapy: A preliminary report
D. MavroudisAlexandros ArdavanisIoannis BoukovinasIoannis VarthalitisK. SyrigosAnna PotamianouCharalambos KouroussisVassilis Georgoulias
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658 Background: Both Vinorelbine plus Gemcitabine (VG) regimen and Capecitabine (C) monotherapy are active salvage treatments in patients (pts) with advanced breast cancer (ABC). In this multicenter study we compared the efficacy and tolerability of the two regimens as salvage treatment in pts with ABC pretreated with taxane and anthracycline chemotherapy. Methods: Pts were randomized to receive either vinorelbine 25 mg/m 2 plus gemcitabine 1000 mg/m 2 (VG) both on day 1 in cycles every 2 weeks or capecitabine 1250 mg/m 2 (C) twice a day on days 1–14 in cycles every 3 weeks. The primary end point of the study was to compare the time to disease progression (TTP). Results: A total of 114 pts were randomized to VG (n=60) and C (n=54). All pts were evaluable for toxicity and 58 VG and 54 C pts for response. Seven (VG) vs 9 (C) pts had stage IIIB disease and 6 vs 5 pts had PS 2. We observed one complete response on each arm and 14(24%) vs 12(22%) partial responses for an overall response rate of 25.8% vs 24.1% (p=0.8) in VG vs C pts, respectively. The median duration of response was 5 vs 12 months (p=0.02) and the median TTP 3.7 vs 5.8 months (p=0.4) for VG and C pts, respectively. A total of 339 VG and 270 C cycles were administered with no toxic deaths. Both regimens were overall well tolerated; grade 3–4 neutropenia 17% vs 4% (p=0.02), anemia 4% vs 2% (p=0.6), grade 3 thrombocytopenia 2% vs 2%, neurotoxicity 3% vs 2%, grade 2–4 hand-foot syndrome 2% vs 15% (p=0.009) for VG and C pts, respectively. Conclusions: In this preliminary analysis the VG and C regimens showed similar activity but different although rarely severe toxicity. Updated results will be presented at the meeting. No significant financial relationships to disclose.Keywords:
Vinorelbine
Taxane
Tolerability
Regimen
Salvage therapy
Clinical endpoint
Chemotherapy regimen
Metastatic breast cancer (BC) remains an incurable disease and clinical benefit and prolongation of time to progression are the main end-points in advanced setting. A safe and feasible schedule of administration is the principal option in pre-treated and symptomatic patients, as in the elderly too. Oral vinorelbine represents a good choice for its toxicity profile and activity in anthracycline and taxane-pre-treated BC patients. A 20–30% response rate (RR) can be obtained when used as single agent. In phase II trials, involving fit patients, and when oral vinorelbine is used in combination with other agents (e.g., capecitabine) a RR of 50-60% has been observed. In HER2-positive BC a combination of oral vinorelbine and trastuzumab has a dramatic activity in first-line therapy and is a reasonable choice in trastuzumab pre-treated patients. In conclusion, oral vinorelbine represents a pivotal choice in advanced and pre-treated BC both as single agent and in combination with others.
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It is reported that the single-agent administration of vinorelbine (VNR) is improper in salvage therapy for non-small cell lung cancer. However, there are few reports on its use as second line in taxane-containing chemotherapy. We used single-agent VNR administration for nine cases of taxane-resistant non-small cell lung cancer, and an antitumor effect was seen in four cases. We present three of these cases. A factor for the high response rate is considered to be that vinca alkaloid is not used as a pre-treatment. Moreover, VNR may be effective even if there is a gene mutation for beta tubulin, which causes taxane resistance.
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Metastatic breast cancer (BC) remains an incurable disease and clinical benefit and prolongation of time to progression are the main end-points in advanced setting. A safe and feasible schedule of administration is the principal option in pre-treated and symptomatic patients, as in the elderly too. Oral vinorelbine represents a good choice for its toxicity profile and activity in anthracycline and taxane-pre-treated BC patients. A 20–30% response rate (RR) can be obtained when used as single agent. In phase II trials, involving fit patients, and when oral vinorelbine is used in combination with other agents (e.g., capecitabine) a RR of 50−60% has been observed. In HER2-positive BC a combination of oral vinorelbine and trastuzumab has a dramatic activity in first-line therapy and is a reasonable choice in trastuzumab pre-treated patients. In conclusion, oral vinorelbine represents a pivotal choice in advanced and pre-treated BC both as single agent and in combination with others.
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Objective To evaluate recent efficacy and safety of gemcitabine and vinorelbine combination chemotherapy for patients with anthracycline and taxane-resistant metastatic breast cancer.Methods Twenty nine patients with anthracycline and taxane-resistant metastatic breast cancer were treated with gemcitabine combined with vinorelbine,21-28 days for a cycle;the response was assessed after the second cycle.Results Among 29 patients,there were 0 case CR(complete response),11 PR(partial response),12 SD(stable disease),6 PD(progress disease).The overall response rate(RR=CR+PR) was 37.9%,clinical benefit rate(CR+PR+SD) was 55.2%.The main toxicity was myelosuppression and gastrointestinal reactions.Conclusion Gemcitabine combined with vinorelbine is active in the treatment of anthracycline and taxane-resistant metastatic breast cancer with acceptable toxicity,and may be an effective salvage therapy.
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Objective To explore the relationship between HER-2 expression and the efficacy of different breast cancer adjuvant chemotherapy for screening of effective chemotherapy.Methods 308 cases ofⅠ-Ⅲ breast cancer patients were adjuvant chemotherapyed with three kinds of programs of anthracycline and(or) taxane,HER-2 expression was detected by immunohistochemistry SP samples,the median follow-up 45.00(13.2 ~ 94.1) months,and analysis the relationship among chemotherapy and pathological features(HER-2 status,hormone receptor status,pathological stage) and the survival rate.Results Overall recurrence rate 22.07%(68/308),the average time to progression 27.58 months.In HER-2 positive patients,disease-free survival in anthracycline chemotherapy groupis DFS(135/191),in taxane group chemotherapyis DFS(15/16),and the difference was significant(x2= 3.938,P0.05);the difference between DFS(35/39) in Anthracycline-taxane combination group and that in anthracycline chemotherapy group was significant(x2 = 6.104,P 0.05).In hormone receptor-positive patients,the difference between DFS(116/165) in anthracycline-chemotherapy group and DFS(19/20) in taxol chemotherapy was significant(x2=5.517,P0.05).In the axillary lymph node-positive patients,the difference of the disease-free survival between DFS(73/113) in anthracycline chemotherapy group and DFS17/19 in taxane chemotherapy was significant(x2=4.638,P0.05);the difference between DFS(36/41) in anthracycline-taxane combination group and that in anthracycline was significant(x2 =7.831,P 0.01).Conclusion Breast cancer patients of HER-2 positive were more sensitive to taxane chemotherapy drug,The efficacy of taxane on the hormone receptor-positive patients is better than that of anthracycline,and the efficacy of taxane and anthracycline on the hormone receptor-negative patients was not significantly different.The efficacy of anthracycline-taxane combined and taxane on lymph node-positive is better than that in anthracycline,and the efficacy of anthracycline and taxane and the combined drugs on lymph node-negative is rather.
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Abstract Background: Anthracycline and taxane-containing chemotherapy regimens reduce the rate of breast cancer recurrence by about one third compared to no chemotherapy. However, concerns about the increased risks of cardiac toxicity and leukaemia with anthracyclines have resulted in wider use of taxane chemotherapy schedules without anthracycline, in particular docetaxel-cyclophosphamide (DC). The benefits and risks of this approach have been assessed in several randomised trials but with conflicting results. Methods: We did an individual patient-level meta-analysis of data on 16,500 participants from 13 randomised controlled trials starting before 2010. Four compared 6 courses of DC with and without concurrent anthracycline (Anth), six compared sequential Anth then taxane (3 or 4 courses of Anth then 3 or 4 D, or vice versa) versus 6 courses of DC (resulting in a higher cumulative dose of taxane in the DC group), and 3 compared sequential Anth + D versus other taxane schedules. Primary outcomes were time to invasive breast cancer recurrence (distant, loco-regional, or new contralateral breast primary) and breast cancer mortality (by log-rank subtraction). Log-rank analyses were used to assess the first-event-rate ratio (RR) and confidence intervals. Pre-specified subgroup investigations included site of recurrence, age, ER/PR status, nodal status, tumor diameter, grade and HER2 status. Results: Overall, patients treated with an anthracycline and taxane combination averaged 18% lower rates of breast cancer recurrence (RR 0.82, 95%CI 0.75-0.90; p<0.0001) than those receiving a taxane schedule without anthracycline, equating to an absolute reduction of 3.1% (95%CI 1.4-4.8) in 10-year recurrence. The 10-year risk of death from breast cancer was reduced by 1.8% (RR 0.85, 95%CI 0.75-0.95; p=0.006) with no increase in deaths without recurrence. The proportional reduction in recurrence was greatest in trials of concurrent Anth + DC versus DC (RR 0.66, 95%CI 0.55-0.79; p<0.0001), where the only difference between arms was the addition of anthracycline (cumulative dose of doxorubicin≈300mg/m2). By contrast, in trials of sequential Anth + D versus the higher cumulative taxane dose DC regimen there was no significant benefit from Anth (cumulative dose of epirubicin≈300mg/m2): RR 0.93, 95%CI 0.80-1.07; p>0.1. In sub-group analyses of all trials, the benefit of anthracycline and taxane chemotherapy persisted throughout years 0-1, 2-4 and 5-9 with little data beyond year 10. There was a similar and highly significant proportional reduction in recurrence in ER-positive and in ER-negative disease and the RRs for recurrence did not differ significantly by any other pre-specified group including age, nodal status, tumor diameter, grade and HER2 status. There were no significant increases in deaths from cardiovascular disease or leukaemia, though longer follow-up is needed to fully assess risks. Conclusion: The addition of anthracycline to taxane chemotherapy, compared to taxane alone reduced the risk of breast cancer recurrence by 18% with larger proportional reductions in trials of DC ± concurrent Anth, in which the taxane dose was the same in both groups and the cumulative anthracycline dose was higher. Citation Format: Jeremy Braybrooke, Rosie Bradley, Richard Gray, Robert Hills, Zulian Liu, Hongchao Pan, Richard Peto, Joanne Blum, Xiaosong Chen, Bent Ejlertsen, Wolfgang Janni, Ulrike Nitz, Dennis Slamon, Masakazu Toi, Toru Watanabe, Sandra Swain, Jonas Bergh, on behalf of the Early Breast Cancer Trialists Collaborative Group. Taxane with anthracycline versus taxane without anthracycline: An individual patient-level meta-analysis of 16,500 women with early-stage breast cancer in 13 randomised trials [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS2-06.
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Introduction: Chemotherapy is the only systemic treatment option for triple-negative breast cancer (TNBC) patients, and is often used in combination with anthracycline and taxane. However, it was reported that many TNBCs show BRCA dysfunction, and are sensitive to DNA-damaging agents, but tend to be resistant to mitotic poisons, such as taxanes. Case Series: Triple-negative breast cancer patients who underwent neoadjuvant chemotherapy with anthracycline followed by taxane were analyzed. Clinical responses to taxane were evaluated by the percentage of shrinkage in tumor size after anthracycline treatment. BRCAness was analyzed by mutiplex ligation-dependent probe amplification (MLPA) in core-needle biopsy specimens of 7 patients with progressive disease or stable disease after taxane treatment. BRCAness scores of the 7 patients were between 0.779 and 1.000 (0.939 ± 0.084), and all were categorized as having BRCAness. Conclusion: Patients resistant to taxane were categorized as having BRCAness by MLPA. Mutiplex ligation-dependent probe amplification may hence be a promising method to identify TNBC patients with taxane resistance.
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Eribulin mesylate has efficacy in patients who have received ≥2 prior chemotherapies for metastatic breast cancer (MBC) including an anthracycline and taxane. Phase 2 trials showed clinical activity and acceptable tolerability of first-line eribulin (HER2- MBC; Study 206) and eribulin plus trastuzumab (HER2+ MBC; Study 208). Prespecified analyses evaluated efficacy by prior anthracycline and/or taxane use. Patients received eribulin mesylate (1.4 mg/m(2) IV; Days 1 and 8) and, in Study 208, trastuzumab (8 mg/kg IV/Cycle 1, then 6 mg/kg; Day 1) in 21-day cycles. Endpoints included objective response rate (ORR), progression-free survival (PFS), and tolerability. In Study 206 (N = 56), 48 % of patients had received prior anthracycline, 46 % prior taxane, 36 % prior anthracycline and taxane, and 41 % were chemotherapy-naïve. In Study 208 (N = 52), these percentages were 21, 44, 17, and 52 %, respectively. In Study 206, ORR and median PFS were similar for anthracycline-pretreated (25.9 %, 5.8 months), taxane-pretreated (26.9 %, 5.8 months), anthracycline- and taxane-pretreated (25.0 %, 6.7 months), and anthracycline/taxane-naïve patients (30.4 %, 7.6 months). In Study 208, ORR/median PFS were 63.6 %/6.7 months among anthracycline-pretreated patients, 56.5 %/6.8 months among taxane-pretreated patients, 55.6 %/5.9 months among anthracycline- and taxane-pretreated patients, and 81.5 %/13.1 months among anthracycline/taxane-naïve patients. Tolerability was generally similar among subgroups. In these studies, first-line eribulin in HER2- MBC and eribulin/trastuzumab in HER2+ MBC was effective with acceptable tolerability, regardless of prior anthracycline/taxane treatment. Prior chemotherapy was associated with lower ORR and shorter PFS with eribulin/trastuzumab in HER2+ MBC but not with eribulin in HER2- MBC.
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