A multicenter, single-arm phase II study of pemetrexed plus doxorubicin administered every 21 days in patients with advanced breast cancer.
BACKGROUND
Doxorubicin and pemetrexed have both shown single-agent activity in breast cancer. Preclinical and clinical evidence indicates that a combination of the 2 agents might have an additive or synergistic effect. A phase II trial was initiated to assess the antitumor activity and safety of pemetrexed plus doxorubicin in women with advanced breast cancer.


METHODS
Anthracycline-naive patients with advanced breast cancer received doxorubicin 50 mg/m(2) plus pemetrexed 500 mg/m(2) (both intravenously) on day 1 of 21-day cycles, as first-line therapy, with standard vitamin supplementation. Seventy-nine women were enrolled (median age, 55.3 years). Seventy-six patients (96.2%) had an Eastern Cooperative Oncology Group performance status of < or = 1.


RESULTS
At baseline, 35 patients (44.3%) had visceral metastases. Three (4.2%) patients were HER2/neu positive, and 30 (42.3%) patients were HER2/ neu negative. The objective response rate was 55.7% (95% exact CI, 44.1%-66.9%), including 2 (2.5%) complete responses. Median progression-free survival was 8 months (95% CI, 6.5-13.3 months). Two-year survival rate was 61.7% (95% CI, 49.7%-71.6%). Grade 3/4 drug-related toxicities in > or = 10% patients included neutropenia (24.1%) and leukopenia (10.1%).


CONCLUSIONS
In patients with advanced breast cancer, the combination of doxorubicin plus pemetrexed was well tolerated and showed promising antitumor activity that warrants further study.
Martin
Miguel
M
Hospital Universitario San Carlos, Madrid E-28040, Spain. mmartin@geicam.org
Blasinska-Morawiec
Maria
M
Salas
J Fernando
JF
Falcon
Silvia
S
Rolski
Janusz
J
Ferrari
Bruno L
BL
Gulyas
Stephen
S
Liu
Yushan
Y
Benhadji
Karim A
KA
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008875:Middle Aged; D000068437:Pemetrexed; D013997:Time Factors; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D004791:Enzyme Inhibitors; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D004317:Doxorubicin