ADDITION OF BEVACIZUMAB TO CAPECITABINE IMPROVES
PROGRESSION-FREE SURVIVAL IN ELDERLY PATIENTS
• The addition of bevacizumab to capecitabine significantly prolonged progression-free survival in elderly
patients with previously untreated metastatic colorectal cancer who were not considered candidates for
oxaliplatin- or irinotecan-based chemotherapy.
• No difference in overall survival was observed between the two groups.
• Adverse events were more common with bevacizumab/capecitabine.
Elderly patients are often underepresented in clinical trials of metastatic colorectal cancer. In a phase III study (AVEX trial)
reported in The Lancet Oncology
, David Cunningham, MD
, of Royal Marsden Hospital
in London and colleagues
assessed the addition of bevacizumab (Avastin) to capecitabine in patients aged ≥ 70 years with previously untreated
metastatic colorectal cancer who were not considered candidates for oxaliplatin- or irinotecan-based chemotherapy.
The bevacizumab/capecitabine combination significantly improved progression-free survival and was associated with more
frequent adverse events than capecitabine alone.
In this international open-label trial, 280 patients were randomly assigned to receive capecitabine 1,000 mg/m2 orally twice
a day on days 1 to 14 alone (n = 140) or with bevacizumab 7.5 mg/kg intravenously on day 1 (n = 140) given every 3 weeks
until disease progression, unacceptable toxic effects, or withdrawal of consent. The primary endpoint was progression-free
Median ages were 76 years in the combination group (61% ≥ 75 years) and 77 years in the capecitabine-alone group (67%
≥ 75 years), and 60% of patients in both groups were male. The groups were generally well matched for baseline charac-
teristics, although more patients in the combination group had undergone surgical resection of the primary tumor (74% vs
64%), received previous adjuvant treatment (completed more than 6 months before the start of study treatment) (32% vs
19%), and been treated with radiotherapy (12% vs 6%).
Prolonged Progression-Free Survival
Median follow-up was 24.8 months for the combination group and 21.6 months for the capecitabine-alone group.
Progression-free survival was significantly longer with bevacizumab/capecitabine (median 9.1 vs 5.1 months, hazard ratio
[HR] = 0.53, P < .0001). Progression-free survival was 66.7% vs 44.2% at 6 months, 34.8% vs 10.3% at 12 months, and
16.2% vs 3.6% at 18 months. Exploratory subgroup analyses of progression-free survival were consistent with the overall
findings. Analysis by age suggested improved outcomes with the combination in patients aged 70 to 74 years (HR = 0.52,
95% confidence interval [CI] = 0.32–0.83), 75 to 79 years (HR = 0.60, 95% CI = 0.40–0.89), and ≥ 80 years (HR = 0.36,
More patients in the combination group achieved response (19% vs 10%, P = .04) and disease control (74% vs 58%, P = .01),
with duration of response being similar in the two groups (median 9.0 vs 9.4 months).
Overall Survival Outcomes
Median overall survival did not differ significantly in the combination vs capecitabine-alone groups (20.7 vs 16.8 months,
HR = 0.79, P = .18). Overall survival was 73.6% vs 60.0% at 1 year and 44.3% vs 35.1% at 2 years. The proportions of
patients who had subsequent treatment after progression were similar in the two groups, including treatment with fluoropy-
rimidine monotherapy (17% vs 18%), bevacizumab (6% vs 8%), irinotecan doublets (6% vs 3%), oxaliplatin doublets (2%
vs 1%), cetuximab (Erbitux; 3% vs 1%), and panitumumab (Vectibix; 1% vs 4%).
Treatment-related adverse events of grade 3 or higher occurred in 40% of patients in the combination group and 22% of
patients in the capecitabine-alone group, and treatment-related serious adverse events occurred in 14% and 8%, respec-
tively. The most common grade 3 or higher adverse events of special interest for bevacizumab or chemotherapy were
hand-foot syndrome (16% vs 7%), diarrhea (7% vs 7%), and venous thromboembolic events (8% vs 4%).
Treatment-related deaths occurred in 3.7% of patients in the combination group and 2.9% in the capecitabine-alone group.
The most common adverse event of any grade of special interest for bevacizumab was hemorrhage (25% vs 7%).
Adverse events led to dose interruption or modification in 55% of combination patients vs 43% of capecitabine patients and
The investigators concluded, “Our data suggest that bevacizumab plus capecitabine represents an additional therapeutic
option in elderly patients with metastatic colorectal cancer, particularly in those who are unsuitable for upfront oxaliplatin-
based or irinotecan-based combination regimens.”
The study was funded by F Hoffmann-La Roche.
CANBERRA FERTILITY CENTRE THE roLE of oEsTraDioL in fEMaLE naTUraL MEnsTrUaL CYCLEs. Oestradiol, also known as oestrogen, is a hormone which plays a central role in the oocyte maturation process, and also plays a secondary role in preparing the uterus for pregnancy. This hormone is found in both the blood and in the follicular fluid (around the oocytes). Levels of oestradiol vary througho
Os efeitos da (des)vinculação dos recursos da União e a flexibilidade orçamentária The effects of (un)binding federal resources and budget flexibility Francisco Hélio de Sousa Conselho de Justiça Federal - CJF - Brasil Resumo O objetivo deste estudo foi observar como a desvinculação de recursos repercute na alocação de recursos da União, bem como seus efeitos sobre a flexi