Randomized phase III trial comparing docetaxel plus epirubicin versus docetaxel plus capecitabine as first-line treatment in women with advanced breast cancer.

BACKGROUND: The purpose of this study was to compare docetaxel plus epirubicin versus docetaxel plus capecitabine combinations as front-line treatment in women with advanced breast cancer (ABC). PATIENTS AND METHODS: Previously untreated patients with ABC were randomly assigned to receive docetaxel 75 mg/m(2) plus epirubicin 75 mg/m(2) (DE) on day 1 or docetaxel 75 mg/m(2) on day 1 plus capecitabine 950 mg/m(2) orally twice daily on days 1-14 (DC) in 21-day cycles. Previous anthracycline-based (neo)-adjuvant chemotherapy was allowed if completed >1 year before enrollment. The primary objective of the study was to compare time to disease progression (TTP). RESULTS: One hundred and thirty-six women were treated on each arm and median TTP was 10.6 versus 11.0 months (P = 0.7), for DE and DC, respectively. According to RECIST criteria we observed 15 (11%) versus 11 (8%) complete responses and 55 (40%) versus 61 (45%) partial responses (P = 0.8), with DE and DC, respectively. Severe toxicity included grade 3-4 neutropenia (57% versus 46%; P = 0.07), febrile neutropenia (11% versus 8%; P = 0.4), hand-foot syndrome (0% versus 4%; P = 0.02), grade 2-3 anemia (20% versus 7%; P = 0.001) and asthenia (12% versus 6%; P = 0.09) with DE and DC, respectively. CONCLUSIONS: The DE and DC regimens have similar efficacy but different toxicity. Either regimen can be used as front-line treatment of ABC.

Combination of irinotecan (CPT-11) plus 5-fluorouracil and leucovorin (FOLFIRI regimen) as first line treatment for elderly patients with metastatic colorectal cancer: a phase II trial.

PURPOSE: To evaluate the efficacy and tolerance of irinotecan (CPT-11) in combination with bolus and continuous infusion of 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFIRI regimen) as first-line treatment of elderly patients with metastatic colorectal cancer (MCC). METHODS: Thirty consecutive, previously untreated patients with metastatic colorectal cancer, aged (median 76 years; range 70-84) were enrolled. The performance status (WHO) was 0 in 8, 1 in 16 and 2 in 6 patients; 19 (63%) patients had prior surgery and 8 (27%) adjuvant chemotherapy. CPT-11 (180 mg/m(2) as a 90 min i.v. infusion) was administered on day 1, LV (200 mg/m(2) as a 2-hour i.v. infusion), 5-FU (400 mg/m(2)/d i.v. bolus followed by 600 mg/m(2)/d as a 22-hour i.v. continuous infusion) were given on days 1 and 2 every 2 weeks. RESULTS: Complete response was achieved in one (3.3%) patient and partial response in 10 (33.3%) (overall response rate: 36.6%; 95% C.I.: 26.6-48.4%); 11 (36.6%) patients had stable disease and, 8 (26.6%) disease progression. The median duration of response was 7.5 months and the median time to disease progression 7.0 months. After a median follow-up period of 17 months, the median overall survival was 14.5 months. Main toxicities were: grade 3-4 neutropenia (n = 6; 20%), grade 3 thrombocytopenia (n = 1; 3.3%), grade 2 anemia (n = 9; 30%), grade 3-4 diarrhea (n = 5; 17%) and grade 3 asthenia (n = 3; 10%). There was one treatment-related death due to neutropenic sepsis. CONCLUSIONS: The FOLFIRI combination is an active regimen with manageable toxicity as front-line treatment in patients above 70 years of age.

Salvage chemotherapy with high-dose leucovorin (LV) and 48-hour continuous infusion (CI) of 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) in patients with metastatic breast cancer (MBC) pretreated with anthracycline and taxanes.

The purpose of this study was to evaluate the activity and tolerance of high-dose leucovorin (LV) and infusional 5-fluorouracil (5-FU) in combination with conventional doses of cyclophosphamide (CPM) as salvage chemotherapy in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. 41 patients (median age 59 years) with MBC refractory or resistant to anthracyclines and taxanes were enrolled. The patients' performance status (WHO) was 0 in 10 patients (24%), 1 in 22 (54%), and 2 in 9 (22%). 30 (73%) patients had received 2 or more prior chemotherapy regimens. Cyclophosphamide (600 mg m(-2)) was given i.v. bolus on day 1 and LV (500 mg m(-2) d(-1)) as a 2-h infusion followed by 5-FU (1.5 g m(-2) d(-1)) over a 22 h c.i. for 2 consecutive days. Cyclophosphamide was administered every 28 days while 5-FU/LV every 14 days. In an intention-to-treat analysis, complete response (CR) was achieved in 2 (4.9%) patients and partial response (PR) in 9 (22%) (overall response rate 26.9%; 95% CI: 13.27-40.39%). Stable disease (SD) and progressive disease (PD) were observed in 9 (22%) and 21 (51%) patients, respectively. The overall response rate was 6% and 40% in patients with primary and secondary resistance to anthracyclines/taxanes, respectively (P = 0.047). The median duration of response and the median time to disease progression was 8 and 9.5 months, respectively. The median overall survival was 13 months and the probability for 1-year survival 51%. Grade 3/4 neutropenia occurred in 9 (22%) patients and 4 (9%) patients developed grade 3/4 thrombocytopenia. Non-haematological toxicity was mild. There were no cases of febrile neutropenia, toxic deaths or treatment-related hospital admissions due to toxicity. The combination of high-dose 5-FU/LV with conventional doses of cyclophosphamide is a well tolerated and effective salvage regimen in patients with MBC heavily pretreated with both anthracyclines and taxanes.