Control of cancer-associated inflammation and survival: Results from a prospective randomized phase II trial in gastric cancer.

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Author(s): A. Reichle, A. Lugner, C. Ott, F. Klebl, M. Vogelhuber, A. Berand, R. Andreesen; University Hospital of Regensburg, Regensburg, Germany
Background: An
angiostatic approach was used to assess the impact of anti-inflammatory
therapy in combination with metronomic low-dose chemotherapy.
A randomized multi-institutional phase II trial was designed to select
metronomic chemotherapy (arm A: capecitabine 1 g orally twice daily for
14 days with one week break until tumor progression) or combined
anti-inflammatory/angiostatic treatment (arm B: capecitabine as
mentioned above plus etoricoxib 60 mg orally, day 1+, and pioglitazone
60 mg orally, day 1+) for further evaluation. Patients with refractory
or progressive disease following any first-line therapy except
capecitabine or frail were eligible. According to the one stage design,
a sample size of 64 patients was calculated for the primary objective,
improvement of response rate.
Results: As similar response
rates were observed (arm A/B 15/14%) after the accrual of 42 patients,
the study was closed (n=20 (A), n=22 (B); median age 69 years (range 46
to 86ys); frail A/B n=9/11). Median progression- free survival for arm
A/B was 3.0/2.9 months (P=0.878), and overall survival 5.0/6.1 months
(P=0.778). In both treatment arms a significant decline of serum
C-reactive protein (CRP) levels was observed within the first 4 to 6
weeks on treatment, A/B P= 0.01/0.04, respectively. CRP response >
50% from baseline was associated with a significantly improved overall
survival in arm A/B (3.1 versus 11.0 months, P= 0.023/ 3.3 versus 7.1
months, P= 0.078) indicating an impact of inflammation-control on
survival. WHO grade 3 (no grade 4) toxicities were reported in arm A/B
in 20% and 23%, respectively, mostly due to hand-foot-syndrome.
Metronomic low- dose chemotherapy in gastric cancer may induce
anti-inflammatory response, but the chosen additional anti-inflammatory
approach neither has impact on tumor-associated inflammation nor on
response or survival rate. In a historical comparison, CRP-responder
have similar outcome as patients treated with combination chemotherapy
in first-line.