Randomised phase II trial of gemcitabine plus vinorelbine vs gemcitabine plus cisplatin vs gemcitabine plus capecitabine in patients with pretreated metastatic breast cancer

Abstract

Background:An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory.Methods:Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m−2 plus vinorelbin 25 mg m−2 on days 1+8 (GemVin), or plus cisplatin 30 mg m−2 on days 1+8 (GemCis), or plus capecitabine 650 mg m−2 b.i.d. orally days 1–14 (GemCap), q3w. The primary end point was response rate.Results:A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ⩾grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand–foot syndrome in 2.0% of the GemCap patients (per patient analysis).Conclusions:This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015

“…Several randomized phase II and III studies have been conducted for MBC patients evaluating the combination therapy versus monotherapy or sequential therapy, and they reported conflicting results [34,35,36,37]. In a phase III trial, the combination therapy was superior to the single agent vinorelbine in both PFS and ORR, with manageable toxicities; however, there was no difference in OS, and the regimen led to more hematologic toxicities [37].…”

“…In a phase II study comparing gemcitabine and vinorelbine combination therapy with sequential monotherapy (gemcitabine followed by vinorelbine), there was no difference in efficacy between the two arms, but patients in the combination arm experienced an improved quality of life with similar adverse events [36]. In a randomized phase II trial comparing gemcitabine plus vinorelbine, gemcitabine plus cisplatin, and gemcitabine plus carboplatin in pretreated MBC patients, no significant differences were found between these arms regarding treatment efficacy [35]. Another phase III study of combined vinorelbine and gemcitabine versus single-agent capecitabine demonstrated no superiority of the combined therapy over the single agent regarding ORR, PFS, and OS [34].…”

Management of the Case of a Young Female Patient with Multiple Malignancies and Germline R24P CDKN2A Gene Mutation

“…A polychemotherapy regimen found active both in pancreatic cancer [12] and breast cancer [13,14] was selected as neoadjuvant chemotherapy for the pancreatic cancer and as adjuvant chemotherapy for the breast tumor. We speculate that the role of the inherited gene mutation can not be excluded in the unexpectedly good response of the advanced pancreatic and breast cancers to chemotherapy.…”

Triple Negative Breast Cancer: A Review of Clinicopathologic Characteristics And Treatment Options

“…Other non-cross-resistant agents such as gemcitabine and vinorelbine are used as single agents after failure of anthracycline/taxane in TNBC, with pCR rates ranging from 28 to 40% compared to 3-14% without gemcitabine or vinorelbine [55][56][57]. Epothilone B ixabepilone and Eribulin recently gained FDA approval for the treatment of advanced disease and have been shown to be efficacious in TNBC patients [58,59].…”