Phase II Study of Recombinant Antitumor and Antivirus Protein Injection Compared With Placebo in Metastatic Colorectal Cancer After Failure of Standard Treatment.
CONCLUSIONS
Novaferon showed moderate efficacy and was well-tolerated in patients with metastatic colorectal cancer (mCRC), especially with the 20 μg injected 3 times a week strategy.Although Novaferon did not provide a survival benefit for mCRC patients who have failed standard treatment, it may play a role in improvement of immune function.


BACKGROUND
To observe the efficacy, safety, and optimal dosage of recombinant antitumor and antivirus protein (Novaferon) in treating patients with metastatic colorectal cancer (mCRC) who failed at least two prior palliative regimens.


METHODS
We enrolled 108 patients from May 2011 to December 2012. According to different treatment modalities and therapeutic dosages, the participants were randomly divided into four cohorts at a 2:2:2:1 ratio: (a) 20 μg Novaferon (Genova Biotech, Beijing, People's Republic of China, http://www.genovabiotech.net) injected twice per week, (b) 20 μg Novaferon injected 3 times per week, (c) 40 μg Novaferon injected 3 times per week, or (d) saline injected 3 times per week. The primary endpoint was overall survival.


RESULTS
There was no significant difference in overall survival among the four cohorts. The 20-μg dose of Novaferon injected 3 times per week had the highest disease control rate (44.0%) at 6 weeks but without significant differences when compared with placebo (p = .159). Major adverse events with Novaferon were influenza-like symptoms, bone marrow suppression, liver dysfunction, and gastrointestinal discomfort. The level of natural killer cells increased and regulatory T cells decreased significantly after treatment with Novaferon, whereas levels in the placebo group remained the same.


CONCLUSIONS
Novaferon showed moderate efficacy and was well tolerated in patients with mCRC, especially with the 20-μg dose injected 3 times per week. Furthermore, Novaferon might improve immune function of these patients.
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China;
Ru
R
Jia
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China;
Yan
Y
Wang
Aviation General Hospital of China Medical University, Beijing, People's Republic of China;
Xiao-Yang
XY
Mao
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China;
Shan-Shan
SS
Li
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China;
Nong
N
Xu
The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China;
Jian-Ping
JP
Xiong
Peking University Cancer Hospital and Institute, Beijing, People's Republic of China;
Lin
L
Shen
General Hospital of the Chinese People's Liberation Army, Beijing, People's Republic of China;
Li
L
Bai
The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
Wei
W
Liu
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China;
Lie-Jun
LJ
Liu
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China;
Fei-Jiao
FJ
Ge
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China;
Yu-Ling
YL
Chen
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China;
Li
L
Lin
Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, People's Republic of China; jmxu2003@163.com.
Jian-Ming
JM
Xu
D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology*; D005260:Female; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D017211:Treatment Failure
D011994:Recombinant Proteins; D007372:Interferons; C000605797:recombinant interferon alpha 2b-like protein