CAMPTOSAR pivotal trials established a standard for overall
survival in metastatic colorectal cancer (mCRC) -With bolus 5-FU/LV:
14.8 months1; with infusional 5-FU/LV: 17.4
months2
Phase 3, randomized, placebo-controlled, clinical trial
(Hurwitz et al)3 of CAMPTOSAR + bolus 5-FU/LV + bevacizumab
as 1st-line treatment of patients with metastatic carcinoma of the
colon or rectum. CAMPTOSAR + bolus 5-FU/LV + bevacizumab was compared
with CAMPTOSAR + bolus 5-FU/LV alone and with bolus 5-FU/LV +
bevacizumab. Primary end point was OS. Secondary end points were
progression-free survival (PFS), response rate, duration of response,
safety, and quality of life.
In a subpopulation (Hurwitz et al, Fyfe et
al)3,4
OS in patients 65 and over who received irinotecan, fluorouracil, and
leucovorin (IFL) + bevacizumab 1st line (n=130) was
24.2
months
Subset analysis of Hurwitz et al was performed to determine the
effect of treatment in patients 65 and over (Fyfe et al).3 Patients who
received IFL + placebo (n=141) had a median duration of survival of
14.9 months.
Particular caution should be exercised in monitoring the effects of
CAMPTOSAR in the elderly (>65).
In a subpopulation (Hurwitz et al, Hedrick et
al)3,5
Subset analysis of Hurwitz et al was performed to determine the
effect of 2nd-line treatment on PFS and OS in patients who received
CAMPTOSAR + bolus 5-FU/LV + bevacizumab (n=402) vs CAMPTOSAR + bolus
5-FU/LV (n=411) 1st line. OS was evaluated in subsets of these
treatment arms that did (n=206) and did not (n=247) include oxaliplatin
2nd line. Use and composition of post-progression therapy (PPT) were at
the discretion of the investigator. Patients who received
non-oxaliplatin PPT did not receive the same degree of benefit 2nd line
as those receiving oxaliplatin 2nd line.
View the
safety information related to this study.
Important safety considerations: bevacizumab6
Bevacizumab administration can result in the development of
gastrointestinal perforation and wound dehiscence, in some instances
resulting in fatality. Gastrointestinal perforation, sometimes
associated with intra-abdominal abscess, occurred throughout treatment
with bevacizumab (ie, was not correlated to duration of
exposure).
Serious, and in some cases fatal, hemoptysis has occurred in patients
with nonsmall cell lung cancer treated with chemotherapy and
bevacizumab. Patients with recent hemoptysis should not receive
bevacizumab.
Arterial thromboembolic events occurred at a higher incidence in
patients receiving bevacizumab in combination with chemotherapy as
compared to those receiving chemotherapy alone.
References: 1. Saltz LB, Cox JV, Blanke C, et al, for the
Irinotecan Study Group. Irinotecan plus fluorouracil and leucovorin
for metastatic colorectal cancer. N Engl J Med.
2000;343:905-914. 2. Douillard JY, Cunningham D, Roth AD, et al.
Irinotecan combined with fluorouracil compared with fluorouracil
alone as first-line treatment for metastatic colorectal cancer: a
multicentre randomised trial. Lancet. 2000;355:1041-1047. 3.
Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus
irinotecan, fluorouracil, and leucovorin for metastatic colorectal
cancer. N Engl J Med. 2004;350:2335-2342. 4. Fyfe GA,
Hurwitz H, Fehrenbacher L, et al. Bevacizumab (AvastinTM)
plus irinotecan/5-fluorouracil/leucovorin for treatment of metastatic
colorectal cancer results in survival benefit in all prespecified
patient subgroups. Poster presented at: Annual Meeting of the
American Society of Clinical Oncology; June 5-8, 2004; New Orleans,
La. Poster 3617. 5. Hedrick EE, Hurwitz H, Sarkar S, Griffing S,
Novotny W, Grothey A. Post-progression therapy (PPT) effect on
survival in AVF2107, a phase III trial of bevacizumab in first-line
treatment of metastatic colorectal cancer (mCRC) [abstract]. J
Clin Oncol. 2004;22(July 15 suppl 14S):3517. 6. Avastin [package
insert]. South San Francisco, Calif: Genentech, Inc; 2006.