Role of Gemcitabine in the Treatment of Advanced and Metastatic Breast Cancer

Abstract

Gemcitabine is an antimetabolite drug with proven antitumor activity and tolerability in metastatic breast cancer. In a total of nine studies, gemcitabine monotherapy has reached response rates of up to 37% in the first-line setting, 26% in the second-line setting, and 18% or better in the third-line setting. Gemcitabine is an excellent choice for combination therapy by its unique mechanism of action and favorable toxicity profile, thus limiting the risk of pretreatment-related drug resistance and overlapping toxicity, and by its potential for synergistic interaction with some combination partners as indicated in preclinical studies. Numerous phase II clinical studies have combined gemcitabine with other active agents such as the taxanes, vinorelbine, vindesine, cisplatin, 5-fluorouracil, as well as anthracyclines across various regimens and conditions of pretreatment. Most of these two-drug combinations have consistently demonstrated higher efficacy than either single agent, particularly in pretreated patients. Even higher efficacy has been obtained with triple-drug regimens including gemcitabine, anthracyclines (epirubicin or doxorubicin), and paclitaxel; these regimens have yielded overall response rates of 58-92% as first-line treatment. In view of these results, gemcitabine may be regarded as a valuable alternative to the palliative treatment of metastatic breast cancer, and an excellent option for the development of effective combination treatment not only in first-line therapy, but also for intensively pretreated patients previously exposed to anthracyclines and/or the taxanes.

Phase II Study of Gemcitabine plus Cisplatin in Patients with Anthracycline- and Taxane- Pretreated Metastatic Breast Cancer

“…Although anthracycline and the taxane are the most active first-line drugs for treatment, the cancers of many patients will progress and require the use of other chemotherapeutic agents (3). Among several agents that have been used, gemcitabine and platinum compounds have been well-characterized single agents (4,5), but there are few studies about the use of a combination of these two types of chemotherapeutic agents. Synergism between gemcitabine (a compound that inhibits DNA repair) and cisplatin (a compound that induces DNA damage) has been demonstrated in in vitro studies (6).…”

A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling

“…Gemcitabine has demonstrated singleagent activity in breast cancer (Heinemann, 2003), and is indicated as first-line therapy in combination with paclitaxel for patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy (Albain et al, 2004). In the neoadjuvant setting, gemcitabine has been combined with anthracyclines and/or taxanes in several phase II studies of locally advanced breast cancer, with clinical response rates and pCR rates ranging from 71 -95% and 3 -26%, respectively (Gomez et al, 2001;Silva et al, 2002;Schneeweiss et al, 2004).…”

A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors

“…Gemcitabine and cisplatin have demonstrated response rates of 29-62% in previously treated advanced breast cancer patients in the phase II setting; however, a high incidence of thrombocytopenia (up to 32%) was observed necessitating gemcitabine dose reduction [14,22,40]. The two responding breast cancer patients in this study were heavily pre-treated with prior chemotherapy but neither had any prior cisplatin, and the patient with a CR did not receive prior gemcitabine.…”