Safety · Oncolytic virotherapy
Side effects of H101,
mostly fever, mostly short-lived.
In the Phase III trial and later combination studies, fever was the dominant side effect of H101. In the PD-1 pilot it typically started within 12 hours and settled within hours without treatment. Here are the published numbers by setting.
Quick answer
What are the side effects of oncolytic virus therapy?
For H101 (Oncorine), the Phase III trial reported fever (45.7%), injection-site reactions (28.3%) and flu-like symptoms (9.8%) as the main side effects. Combined with TACE for liver cancer, the only side effect significantly more frequent than with TACE alone was fever above 38.5 °C (64.4% vs 46.6%). In an 18-patient study combining H101 with the PD-1 drug nivolumab, every patient had low-grade fever and no grade 3–4 events were reported.
45.7%
Fever, Phase III
Main side effect with intratumoral H101 + chemotherapy
Xia et al., Ai Zheng 2004
28.3%
Injection-site reaction
Phase III trial
Xia et al., Ai Zheng 2004
9.8%
Flu-like symptoms
Phase III trial
Xia et al., Ai Zheng 2004
64.4% vs 46.6%
Fever > 38.5 °C with TACE
TACE + H101 vs TACE alone, P = 0.023
Lin et al., BMC Cancer 2015
0
Grade 3–4 with nivolumab
H101 + nivolumab pilot, n=18
Yi et al., ESMO Open 2024
27.5%
Fever, intraperitoneal
Malignant ascites, n=40; abdominal pain 20%
Zhang et al., Mol Ther Oncolytics 2022
What to expect
Common side effects reported in studies.
Fever
Reported in every setting studied. In the nivolumab pilot it typically occurred within 12 hours of injection and mostly subsided after 2–4 hours without special treatment.
Mostly grade 1–2
Injection-site reaction / pain
Injection-site reactions occurred in 28.3% in the Phase III trial, and injection-site pain in 33.3% in the nivolumab pilot.
Local
Flu-like symptoms & fatigue
Flu-like symptoms affected 9.8% in the Phase III trial. Fatigue and reduced appetite each affected 11.1% in the nivolumab pilot.
Usually mild
Abdominal pain
In the malignant-ascites series, 17.5% had mild-to-moderate abdominal pain and 2.5% (one patient) severe abdominal pain.
20% overall
Lab changes
Raised bilirubin, ALT/AST, raised TSH and low phosphate each affected 11.1% in the nivolumab pilot. The authors considered some to be immune-related effects of the combination.
Blood tests
By setting
Published adverse-event data
Side-effect rates depend heavily on what H101 is combined with. The table summarises the main published figures by setting.
| Setting (study) | Patients | Main findings |
|---|---|---|
| Intratumoral + chemotherapy, head & neck / oesophageal SCC (Xia 2004, Phase III) | 160 enrolled | Fever 45.7%, injection-site reaction 28.3%, flu-like symptoms 9.8% |
| Hepatic artery + TACE, unresectable HCC (Lin 2015) | 87 vs 88 | Fever > 38.5 °C 64.4% vs 46.6% (P = 0.023); pain, ascites and acute renal failure not different; no encephalopathy |
| Hepatic artery + TACE, unresectable HCC (Dong 2014) | 149 vs 150 | Overall treatment-related adverse effects similar; no serious complications |
| Intratumoral + nivolumab, refractory HCC (Yi 2024) | 18 | All events grade 1–2; fever 100%, injection-site pain 33.3%, cancer pain 16.7% |
| Intraperitoneal, malignant ascites (Zhang 2022) | 40 | Fever 27.5%, abdominal pain 20%; no grade III/IV per abstract |
Before treatment
What your oncologist will check
The drug label restricts H101 to Class A tertiary (三级甲等) hospitals. In the liver-cancer studies, eligible patients had Child-Pugh A or B liver function and adequate kidney function (serum creatinine below 140 µmol/L, BUN within normal range).
Before treatment, expect a review of your liver and kidney function, blood counts, current medicines and other illnesses. Ask the treating team directly about any condition that worries you, such as immune suppression, active infection or pregnancy. Their answer should be based on the full prescribing information and your records.
FAQ
Oncolytic virus safety — answered.
- Is oncolytic virus therapy safe?
- In the published H101 studies, side effects were mostly fever and local reactions. Combined with TACE, it did not increase pain, ascites or acute renal failure compared with TACE alone. Combined with nivolumab in 18 patients, no grade 3–4 events were reported. Small studies cannot rule out rare risks, and suitability depends on your overall health, so treatment should be given by an experienced oncology team.
- Is the virus contagious? Can I infect my family?
- We have not found peer-reviewed viral-shedding data for H101 that we could verify, so we won't make a claim either way. Hospitals handle the drug and treated sites under their own biosafety procedures. Ask the treating team what precautions, if any, apply at home.
- Why do I get a fever after the injection?
- Fever is the most consistently reported effect of H101 and is generally viewed as a response to the virus. In the nivolumab pilot it typically began within 12 hours and subsided after 2–4 hours without special treatment. Persistent or very high fever should be reported to the team.
- Does H101 cause hair loss like chemotherapy?
- Hair loss is not among the side effects reported for H101 in the studies above. When H101 is combined with chemotherapy or TACE, those treatments carry their own side effects, which your oncologist will explain.
Related guides
Oncolytic Virus Therapy (hub)
Overview: what it is, who it may suit, how it's used in China.
Read the guideOncorine (H101) drug profile
Approval, genetic construct, approved indication and milestones.
Read the guideHow oncolytic viruses work
Selective replication, tumour lysis and turning 'cold' tumours 'hot'.
Read the guideH101 + TACE for liver cancer
Evidence, guideline status and treatment protocol for HCC.
Read the guideH101 + PD-1 immunotherapy
Combination data, malignant ascites and immune-microenvironment changes.
Read the guideClinical evidence & guidelines
Key studies, ASCO 2024 abstracts and three Chinese consensus documents.
Read the guideOncology second opinion
Senior Chinese oncologist reviews your imaging and pathology remotely.
Read the guideSources
References
- Oncorine (重组人5型腺病毒注射液) prescribing information, 国药准字 S20060027 — indication: advanced nasopharyngeal carcinoma unresponsive to radiotherapy or chemoradiotherapy, in combination with 5-FU/cisplatin palliative chemotherapy; construct: E1B-55kD and E3 (78.3–85.8 mu) gene fragments deleted.
- Xia ZJ, Chang JH, et al. Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus. Ai Zheng. 2004;23(12):1666–1670.
- Lin XJ, Li QJ, Lao XM, Yang H, Li SP. Transarterial injection of recombinant human type-5 adenovirus H101 in combination with transarterial chemoembolization (TACE) improves overall and progressive-free survival in unresectable hepatocellular carcinoma (HCC). BMC Cancer. 2015;15:707.
- Dong J, et al. Gene therapy for unresectable hepatocellular carcinoma using recombinant human adenovirus type 5. Med Oncol. 2014;31(8):95.
- Yi L, Ning Z, Xu L, et al. The combination treatment of oncolytic adenovirus H101 with nivolumab for refractory advanced hepatocellular carcinoma: an open-label, single-arm, pilot study. ESMO Open. 2024;9(2):102239.
- Zhang Y, Qian L, Chen K, et al. Intraperitoneal oncolytic virotherapy for patients with malignant ascites: characterization of clinical efficacy and antitumor immune response. Mol Ther Oncolytics. 2022;25:31–42.
- CSCO Immunotherapy Expert Committee; Shanghai Anti-Cancer Association Tumor Biotherapy Committee. 基因重组溶瘤腺病毒治疗恶性肿瘤临床应用中国专家共识(2022年版). China Oncology (中国癌症杂志). 2023;33(5). doi:10.19401/j.cnki.1007-3639.2023.05.013
Concerned about side effects?
Ask a specialist.
Send your medical history and current medicines. A partner oncologist will assess whether H101 is appropriate for you specifically and explain what monitoring a course would involve.
This page is for general education only and is not medical advice. Oncolytic virus therapy is not suitable for every patient or every cancer. In China, Oncorine (H101) is approved only for advanced nasopharyngeal carcinoma in combination with chemotherapy; other uses described here are supported by retrospective studies, small trials, conference abstracts or expert consensus rather than large randomised trials. Treatment decisions are made by the treating oncologist after reviewing your records. We are an independent patient-coordination service and are not affiliated with the manufacturer.