The gemcitabine/epirubicin/paclitaxel trials in advanced breast cancer.
Numerous trials have shown that the pharmacokinetic interferences of epirubicin (Ellence)/paclitaxel (Taxol) combinations produce less pharmacodynamic effect than doxorubicin/paclitaxel regimens. Paclitaxel is more easily combined when infused over 3 (as compared to 24) hours; the administration of optimal doses of both agents is important. Based on these findings, a phase II study was performed to evaluate the feasibility and activity of the combination of gemcitabine (Gemzar), epirubicin, and paclitaxel as first-line therapy in advanced breast cancer. Patients received gemcitabine at 1,000 mg/m2 on days 1 and 4, plus epirubicin at 90 mg/m2 on day 1, plus paclitaxel at 175 mg/m2/d on day 1 every 21 days. After six courses, patients less than 60 years old and in complete or partial remission or stable disease were treated with high-dose chemotherapy as consolidation treatment. The overall response rate was 92%, with 31% complete responses; 25 patients received high-dose chemotherapy, achieving a final overall response rate of 97%, with 47% complete responses. At a median follow-up of 25 months, median progression-free survival is 21 months. Grade 4 neutropenia was observed in 64% of patients. Other hematologic toxicities were mild. Mild to moderate peripheral neuropathy was experienced by 39% of patients; grade 2 or 3 mucositis occurred in 25% and 17% of patients, respectively. Based on these results, a multicenter trial has been started in seven Italian centers to confirm the feasibility of this regimen.
Medical Oncology, S. Chiara Hospital, Pisa, Italy.
P
P
Conte
B
B
Salvadori
S
S
Donati
A
A
Gennari
G L
GL
Cetto
A
A
Molino
L
L
Crino
F
F
Mazzoni
E
E
Galligioni
M
M
Mansutti
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine
D003841:Deoxycytidine; D015251:Epirubicin; D017239:Paclitaxel; D000093542:Gemcitabine