Mitoxantrone Plus Vinorelbine in Pretreated Patients with Metastatic Breast Cancer

Abstract

Vinorelbine and mitoxantrone have both been demonstrated to have significant antitumor activity in patients with breast cancer. The aim of this study was to evaluate the efficacy and safety of the combination as second or third line treatment in patients with metastatic breast cancer (MBC). Fifty-one previously treated patients with MBC were enrolled from October 2001 to May 2004 and 48 were eligible for evaluation. Median age was 59 years (range 33-82) and ECOG performance status was < or =2. Distant sites of metastasis were as follows: liver 64%, bone 49%, lung 36%, lymph nodes 6%, skin 4%, brain 2% and other sites 6%. All patients received vinorelbine 20 mg/m(2), D1+8 and mitoxantrone 10 mg/m(2) D8 every 21 days for 6 cycles. All eligible patients were analyzed for toxicity and response. Two patients (4%) achieved complete response and 12 (25.5%) partial response. The objective overall response rate was 29.5% (95% confidence interval [CI] 17 - 45), 9 (19%) patients had stable disease, 17 (36%) had progressive disease and 7 (15%) were non-evaluable. After a median follow up of 18 months, overall survival was 13 months (range 0.8 - 38+) and median time to disease progression was 5 months (range 1 - 32). A total of 280 cycles was delivered. The relative dose intensities of mitoxantrone and vinorelbine were 79% and 77%, respectively. Toxicities (grade III-IV) were as follows: leukopenia 18 (38%), neutropenia 21 (45%), thrombocytopenia 1 (2%), anemia 4 (8.5%), alopecia 2 (4%) and constipation 1 (2%). Febrile neutropenia was recorded in one patient. There were no treatment related deaths. The combination of mitoxantrone and vinorelbine is an effective regimen with manageable toxicity in pretreated patients with advanced breast cancer.

Second-Line Combination Chemotherapy with Vinorelbine and Capecitabine in Patients with Advanced Breast Cancer Previously Treated with Anthracyclines and/or Taxanes

“…The results of this study are also consistent with those of previous studies evaluating CAP/VRL, as well as other VRL-based combinations (e.g. gemcitabine/VRL [20,21] and mitoxantrone/VRL [22]), in a similar setting. Ahn et al [17] demonstrated ORR of 50%, with median TTP and OS of 5.3 and 17 months, respectively.…”

“…However, Jones et al [23 ]reported RR of 20%, with median TTP and OS of 3.4 and 11.3 months, respectively. Median TTP and OS were 5 and 13 months in a mitoxantrone/VRL combination study [22], and 5.3 and 14 months in gemcitabine/VRL, respectively [21]. Comparable results were also observed by Bunnell et al [24] in a phase II study of ixabepilone plus CAP in anthracycline-pretreated/-resistant and taxane-resistant ABC.…”

Etoposide, mitomycin, and methotrexate combination in heavily treated breast cancer: a retrospective study

“…Myelosuppression was the most common toxicity, with 24 patients (34%) experiencing grade 3-4 anemia, 29 patients (39%) requiring red blood cells transfusions (median 2 units, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14], 32 patients (45%) experiencing grade 3-4 neutropenia. Severe (grade 3-4) thrombocytopenia was observed in 36 patients (51%).…”

“…Currently there is no single standard to guide oncologists in choosing further chemotherapeutic regimens for MBC patients affected with disease progression after anthracycline-, taxane-, and capecitabine-based regimens [1][2][3]. As a result, various new drugs have been tested in this setting, such as vinorelbine, gemcitabine, pemetrexed, or ixabepilone [4][5][6][7][8][9], without any drug or regimen achieving a standard recognition. At the same time, as a result of the changes in adjuvant and metastatic first-line standard regimens, several older drugs have been less extensively used, and thus can be theoretically considered good candidate drugs considering the low risk of crossresistance due to previous chemotherapeutic exposure and to their well-documented efficacy and safety profiles.…”

Oral vinorelbine: its role in advanced breast cancer pre-treated with anthracycline and taxane chemotherapies

“…For all phase II combination studies (including trastuzumab combination in HER2-neu positive setting), the overall tumour RRs ranged from 33 to 75%, median OS from 13 to 35.8 months, median response duration from 2.6 to 17.5 months, median TTP (reported in two studies) from 6.6 to 8.6 months and median PFS (reported in two studies) from 9.6 to 9.9 months. The most commonly reported adverse events attributed to VI were neutropoenia, nausea, vomiting and alopecia [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”