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

Background: This open-label, nonrandomized phase II clinical trial investigated the efficacy of capecitabine-based doublets in the first-line treatment of metastatic triple-negative breast cancer (mTNBC). Methods: Eligible mTNBC women with measurable diseases were recruited to receive either TX regimen (docetaxel 75 mg/m² i.v. on day 1 plus capecitabine 1,000 mg/m² b.i.d. on days 1-14 every 3 weeks) or NX regimen (vinorelbine 25 mg/m² i.v. on days 1 and 8 plus capecitabine 1,000 mg/m² b.i.d. on days 1-14 every 3 weeks) for up to 6 cycles until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and secondary end points included progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR). Results: Forty-five mTNBC patients, 27 in TX and 18 in NX were recruited. The total ORR was 20.0% and CBR was 40%. After a median follow-up of 28 months, PFS was 5.2 months (95% CI, 4.1-6.3 months) and OS was 18.2 months (95% CI, 8.7-27.7 months). The response rate was numerically but not statistically lower in the TX group than in the NX group (27.8 vs. 14.8%, p = 0.449). No difference was found in either PFS (4.9 vs. 5.2 months, p = 0.483) or OS (21.5 vs. 18.3 months, p = 0.964) between the two regimens. Conclusions: Although the OS seems to be reasonable, the efficacy of capecitabine-containing TX or NX regimen was limited in terms of response and PFS in mTNBC patients, suggesting capecitabine-based doublet may be acceptable but has limited potency in this subtype.

Section: Discussionmentioning

confidence: 99%

Acceptable but Limited Efficacy of Capecitabine-Based Doublets in the First-Line Treatment of Metastatic Triple-Negative Breast Cancer: A Pilot Study

Liao

Fan²,

Wan³

et al. 2013

“…This regimen had significant toxicity, with most patients experiencing severe or life-threatening hematologic, renal or infectious complications [121]. The oral agent capecitabine is now an established therapy for MBC, with activity even at low doses, especially when combined with vinorelbine [122,123,124]. The combination of cisplatin with capecitabine was evaluated in two trials recruiting patients with MBC resistant to anthracyclines and taxanes.…”

Section: Experience With Combination Chemotherapymentioning

confidence: 99%

Platinum-Based Compounds for the Treatment of Metastatic Breast Cancer

Shamseddine¹,

Farhat²

2011

The role of platinum-based compounds (PBCs) in the treatment of metastatic breast cancer (MBC) has been extensively studied. As single agents, high response rates have been observed in first-line therapy, while results in pretreated patients were discouraging. Regimens containing cisplatin/carboplatin together with taxanes showed the highest efficacy and safety as both first-line and second-line therapy. When administered with vinorelbine, the combination was also active and well tolerated in anthracycline- and taxane-pretreated patients. Combining PBCs with etoposide or nucleoside analogues showed moderate activity, yet high toxicity in the case of etoposide. The overall results for the combination with anthracyclines were disappointing. Addition of trastuzumab to PBC combinations showed remarkable activity and good tolerability in patients with HER2/neu overexpression. The use of cisplatin or carboplatin alongside novel targeted therapeutics for patients with triple-negative MBC seems promising and is being further evaluated. The use of PBCs against MBC requires careful patient selection and combination with the right chemotherapeutic agent.

“…An additional 6% of patients present with metastatic disease at diagnosis. Advanced breast cancer (ABC) patients form a large population that is in need of effective therapy; in particular, some chemotherapy agents have demonstrated significant efficacy in patients who have previously been exposed to taxanes and anthracyclines [3,4,5]. Vinorelbine is a semi-synthetic vinca alkaloid that induces cytotoxicity by inhibiting microtubule assembly at the G2-M phase, and it has a broad spectrum of antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Therapeutic Efficacy of the Early and the Delayed Use of Vinorelbine-Based Regimens for Patients with Advanced Breast Cancer

Wang

Liu²,

Jia³

et al. 2016

Background: The aim of this study was to evaluate the efficacy of vinorelbine-based regimens as first-, second- and more-line therapies in advanced breast cancer (ABC) and to analyze the best timing of vinorelbine treatment. Methods: A total of 71 ABC patients were retrospectively reviewed. Of these, 35 patients were treated with vinorelbine-based regimens as first-line chemotherapy, and 36 patients were treated with vinorelbine-based regimens as second-line or more-line therapy. The primary end point of the study was progression-free survival (PFS). Results: No difference was found in baseline characteristics between the two groups (p > 0.1 for all comparisons). There was a significant difference in the objective response rate (ORR; p = 0.006) and clinical benefit rate (CBR; p = 0.013) between the first-line group and the second- or more-line groups. In the vinorelbine first-line group, the ORR was 68.6% (24 patients), and in the second-line or more-line groups the ORR was 36.1% (13 patients). A significant difference in PFS between the first-line group and the second-line or more-line groups was also observed (p = 0.030). The median PFS in the overall population was 6.3 ± 1.32 months (95% CI 3.69-8.90). The median PFS was 11.1 ± 3.76 months (95% CI 3.73-18.47) in the first-line group compared with 5.2 ± 1.35 months (95% CI 2.54-7.85) in the second-line or more-line groups. In patients treated with vinorelbine-trastuzumab combination as the first-line therapy, a complete response was observed in 1 patient (12.5%) and partial response in 5 patients (62.5%), giving an ORR of 75.0%. Progressive disease was observed in 1 patient (12.5%), and stable disease in 1 patient (12.5%), leading to a CBR of 87.5%. The median PFS was 13.8 ± 2.75 months (95% CI 8.42-19.18), and median OS was 37.0 ± 11.6 months (95% CI 14.18-59.82). No significant difference was found in overall survival (OS) between the groups (p = 0.612). Conclusion: For ABC patients, no significant difference in median OS was found between the early use and delayed use of vinorelbine-based regimens, but the short-term efficacy and PFS of vinorelbine-based regimens were significantly better in the early use group than in the delayed use group.