Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group.
OBJECTIVE
This phase III study compared docetaxel with mitomycin plus vinblastine (MV) in patients with metastatic breast cancer (MBC) progressing despite previous anthracycline-containing chemotherapy.


METHODS
Patients (n=392) were randomized to receive either docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks (n=203) or mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks (n=189), for a maximum of 10 3-week cycles.


RESULTS
In an intention-to-treat analysis, docetaxel produced significantly higher response rates than MV overall (30.0% v 11.6%; P < .0001), as well as in patients with visceral involvement (30% v 11%), liver metastases (33% v 7%), or resistance to previous anthracycline agents (30% v 7%). Median time to progression (TTP) and overall survival were significantly longer with docetaxel than MV (19 v 1 weeks, P=.001, and 1 1.4 v 8.7 months, P=.0097, respectively). Neutropenia grade 3/4 was more frequent with docetaxel (93.1 % v62.5%; P < .05); thrombocytopenia grade 3/4 was more frequent with MV (12.0% v 4.1%; P < .05). Severe acute or chronic nonhematologic adverse events were infrequent in both groups. Withdrawal rates because of adverse events (MV, 10.1%; docetaxel, 13.8%) or toxic death (MV, 1.6%; docetaxel, 2.0%) were similar in both groups. Quality-of-life analysis was limited by a number of factors, but results were similar in both groups.


CONCLUSIONS
Docetaxel is significantly superior to MV in terms of response, TTP, and survival. The safety profiles of both therapies are manageable and tolerable. Docetaxel represents a clear treatment option for patients with MBC progressing despite previous anthracycline-containing chemotherapy.
Nabholtz
J M
JM
Cross-Cancer Institute, Edmonton, Alberta, Canada. jmarkn@cancerboard.ab.ca
Senn
H J
HJ
Bezwoda
W R
WR
Melnychuk
D
D
Deschênes
L
L
Douma
J
J
Vandenberg
T A
TA
Rapoport
B
B
Rosso
R
R
Trillet-Lenoir
V
V
Drbal
J
J
Molino
A
A
Nortier
J W
JW
Richel
D J
DJ
Nagykalnai
T
T
Siedlecki
P
P
Wilking
N
N
Genot
J Y
JY
Hupperets
P S
PS
Pannuti
F
F
Skarlos
D
D
Tomiak
E M
EM
Murawsky
M
M
Alakl
M
M
Aapro
M
M
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006304:Health Status; D006801:Humans; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage / Q000627:therapeutic use*; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010349:Patient Compliance; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis; D043823:Taxoids; D013921:Thrombocytopenia / Q000139:chemically induced; D014747:Vinblastine / Q000008:administration & dosage / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D008937:Mitomycins; D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D017239:Paclitaxel