Incorporating Angiogenesis Inhibition with Bevacizumab (anti-VEGF) into Frontline Chemotherapy with Irinotecan (CPT-11), Fluorouracil and Leucovorin (FU/LV) for Advanced Colorectal Cancer (advCRC): A Toxicity Analysis of ECOG Study E2200

Reviewer: Thomas Dilling, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 19, 2002

Presenter: B.J. Giantonio
Presenter's Affiliation: University of Pennsylvania
Type of Session: Scientific

Background

Anti-angiogenesis therapy has received much publicity recently.
Such molecularly-targeted therapies hold promise as the next wave of directed therapies against cancer.
Early studies of these therapies have held some promise, but more data is needed.
These investigators conducted a study of Bevacizumab (one of a few anti-angiogenesis agents currently in development), with frontline chemotherapy for advanced colorectal cancer.
Primary endpoints of this Phase II trial are toxicity/tolerability and measurement of response.

Materials and Methods

Recruited patients had previously untreated advanced coclorectal cancer.
Patient treatment consisted of CPT-11 (125 mg/m2), FU (500 mg/m2) and LV (20 mg/m2) weekly for 4 of 6 weeks, with anti-VEGF (10 mg/kg) every other week.
19 patients were initially enrolled. Interim analysis raised concerns about toxicity, however, so the trial was temporarily closed. It later reopened with mild reductions in the chemotherapy dose (no change to the dosing of Bevacizumab).
Toxicity data are now available on the first 60 patients enrolled (the original 19 and 41 patients subsequently enrolled in the amended trial).
Toxicity data are presented here; data regarding tumor response are currently being compiled and are not yet available.

Results

15% of patients had grade 3 diarrhea; none had grade 4.
12% of patients had grade 3 vomiting and 2% had grade 4.
12% had grade 3 nausea.
A total of 33% had grade 3 or grade 4 neutropenia, though only 3 patients had febrile neutropenia.
Overall, these toxicities are equivalent to, or less than, those reported by Saltz, et al. in the literature regarding the chemotherapy regimen alone (minus the anti-VEGF).
The presenter stated, too, that nausea, vomiting, and dehydration was diminished in patients treated on the reduced-dosage chemotherapy regime compared with those treated prior to trial amendment.
There were some mild bleeding events, presumably related to the anti-VEGF agent.
Mild, self-limited epistaxis was fairly common. In addition, one patient had bleeding per rectum (possibly related to the primary tumor) and one had bleeding from a chest wall metastasis. One patient had epistaxis which required tamponade.

Author's Conclusions

Addition of Bevacizumab, an anti-VEGF agent, to a CPT-11 containing chemotherapy regimen, appears safe and well tolerated.

Clinical/Scientific Implications

Treatment with Bevacizumab, in conjunction with a CPT-11-containing chemotherapy regimen, dose not appear to result in untoward toxicity.
It remains to be seen whether this particular anti-VEGF agent produces clinical response in patients. Analysis of this data is ongoing.

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