Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment.

Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, 2160 S First Ave, Maywood, IL 60153, USA.
Journal of Clinical Oncology (Impact Factor: 17.88). 09/2008; 26(24):3950-7. DOI: 10.1200/JCO.2007.11.9362
Source: PubMed

ABSTRACT The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication.
Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m(2) days 1 and 8 plus paclitaxel, 175 mg/m(2) on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival (OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths.
A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT.
This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.
    04/2012; 2012:915375. DOI:10.1155/2012/915375
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chemotherapeutic agents that have shown improved patient outcome when combined with anti-vascular endothelial growth factor (VEGF) therapy were recently identified to induce the mobilization of proangiogenic Tie-2-expressing monocytes (TEMs) and endothelial progenitor cells (EPCs) by platelet release of stromal cell-derived factor 1α (SDF-1α). VEGF blockade was found to counteract cell mobilization. We aimed to determine why agents like gemcitabine do not elicit TEM and EPC recruitment and may therefore lack synergy with anti-VEGF therapy. Locally advanced pancreatic cancer patients (n = 20) were monitored during 16 weeks of neoadjuvant therapy. Treatment was based on gemcitabine with or without the addition of bevacizumab. Blood levels of proangiogenic cell populations and angiogenesis factors were determined in 2-week intervals. The lack of EPC mobilization during gemcitabine therapy was associated with severe thrombocytopenia and reduced SDF-1α blood concentrations. Furthermore, myelosuppression by gemcitabine correlated significantly with loss of TEMs. With respect to angiogenic factors stored and released by platelets, plasma levels of the angiogenesis inhibitor thrombospondin 1 (TSP-1) were selectively decreased and correlated significantly with thrombocytopenia in response to gemcitabine therapy. A thorough literature screen identified thrombocytopenia as a common feature of chemotherapeutic agents that lack synergy with anti-VEGF treatment. Our results on gemcitabine therapy indicate that myelosuppression (in particular, with respect to thrombocytes and monocytes) interferes with the mobilization of proangiogenic cell types targeted by bevacizumab and may further counteract antiangiogenic therapy by substantially reducing the angiogenesis inhibitor TSP-1.
    Neoplasia (New York, N.Y.) 05/2011; 13(5):419-27. DOI:10.1593/neo.101508 · 5.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Incremental advances over the last two decades in the treatment of stage IV metastatic breast cancer (MBC) have resulted in significantly prolonging the average life expectancy. In 2008, the estimated 5-year relative survival rate for MBC is 27% which compares favorably to rates in stage IV lung (3%) and pancreatic cancers (1%). Despite these advances, MBC remains an incurable disease, often associated with many symptoms and a decreased quality of life (QoL). Therefore, therapy goals in the treatment of MBC include prolonging both progression-free survival and overall survival rates, while at the same time improving QoL by palliation of symptoms. Therefore, systemic chemotherapy ideally should not induce unnecessary toxicities. Once chemotherapy is indicated, a number of drugs and regimens are available but only a few offer both palliation of symptoms (responses to therapy) and overall survival benefit. The addition of novel biologic compounds to chemotherapy has been shown in phase III trials to improve all the above mentioned clinical outcomes in MBC. This review will discuss data supporting the use of gemcitabine/taxane combinations in the treatment of MBC.
    Therapeutics and Clinical Risk Management 01/2009; 4(6):1157-64. · 1.47 Impact Factor