Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over.
OBJECTIVE
To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival ¿PFS) and to explore the degree of cross-resistance between the two agents.


METHODS
Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m(2), 3-hour infusion every 3 weeks, or doxorubicin 75 mg/m(2), intravenous bolus every 3 weeks. Seven courses were planned unless progression or unacceptable toxicity occurred before the seven courses were finished. Patients who progressed within the seven courses underwent early cross-over to the alternative drug, while a delayed cross-over was optional for the remainder of patients at the time of disease progression.


RESULTS
Objective response in first-line therapy was significantly better (P =.003) for doxorubicin (response rate ¿RR, 41%) than for paclitaxel (RR, 25%), with doxorubicin achieving a longer median PFS (7.5 months for doxorubicin v 3.9 months for paclitaxel, P <.001). In second-line therapy, cross-over to doxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not significantly different (P =.38). The doxorubicin arm had greater toxicity, but this was counterbalanced by better symptom control.


CONCLUSIONS
At the dosages and schedules used in the present study, doxorubicin achieves better disease and symptom control than paclitaxel in first-line treatment. Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in sequence, both in advanced disease and in the adjuvant setting.
Paridaens
R
R
University Hospital Gasthuisberg, Leuven, Belgium. Robert.Paridaens@uz.kuleuven.oc.be
Biganzoli
L
L
Bruning
P
P
Klijn
J G
JG
Gamucci
T
T
Houston
S
S
Coleman
R
R
Schachter
J
J
Van Vreckem
A
A
Sylvester
R
R
Awada
A
A
Wildiers
J
J
Piccart
M
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary*; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016009:Chi-Square Distribution; D018592:Cross-Over Studies; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D016015:Logistic Models; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012074:Remission Induction; D015996:Survival Rate
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D017239:Paclitaxel