Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study

To investigate the activity of the combination of gemcitabine (G) plus epirubicin (E) and taxol (T), (GET), in metastatic breast cancer, to evaluate the feasibility of this regimen as induction before high dose chemotherapy and to study the pharmacokinetic interactions of these three drugs.

Metastatic breast cancer patients, with bidimensionally measurable disease were eligible. Treatment consisted of G 1000 mg/sqm days 1 and 4 plus E 90 mg/sqm day 1 plus T 175 mg/sqm/3 h day 1, every 21 days. After six courses of GET, patients aged less than 60 years, in complete or partial remission or stable disease entered a programme of high dose chemotherapy (HDCT), as consolidation treatment.

Thirtysix patients were included in this study. Grade 4 neutropenia was observed in 64% of the patients, with four episodes of febrile neutropenia; 39% of the patients experienced mild to moderate peripheral neuropathy; grade 2 and 3 mucositis occurred respectively in 9 (25%) and 6 (17%) patients. The overall response rate to GET was 92% (95% CI, 77.53%-98.25%); CR 31% and PR 61%. After six courses of GET, 25 patients received HDCT, leading to an overall response rate of 96% with 58% CR. At a median follow up of 25 months (range 8-39), 13 out of 36 patients are progression free and 26 alive. Median progression free survival is 21 months, while median overall survival has not yet been reached. The pharmacokinetic data show that G does not influence the interactions between E and T, while gemcitabine kinetics remains unchanged.

The results of the present study indicate that the addition of G to E plus T as front line treatment for advanced breast cancer is well tolerated with an ORR of 92%. On the basis of the high activity and interesting progression free and overall survival rates, the GET combination deserves further evaluation in randomized trials.