No maximally tolerated dose or dose-limiting toxicities were identified at doses up to 2xl012 particles administered by intratumoral injection. Flulike symptoms and injection-site pain were the most common associated toxicities . This safety is remarkable given the daily or even twice-daily dosing that was repeated every 1-3 weeks in the head and neck region or pancreas ,
Intraperitoneal, intraarterial, and intravenous administration were also remarkably well tolerated in general. Intraperitoneal administration was feasible at doses up to 1013 particles divided over 5 days . The most common toxicites included fever, abdominal pain, nausea/vomiting, and bowel motility changes (diarrhea, constipation). The severity of the symptoms appeared to correlate with tumor burden. Patients with heavy tumor burdens reached a maximally tolerated dose at 1012 particles (dose-limiting toxicities were abdominal pain and diarrhea), whereas patients with a low tumor burden tolerated 1013 without significant toxicity.
No dose-limiting toxicities were reported following repeated intravascular injection at doses up to 2 x 1012 particles (hepatic artery)  or 2 x 1013 particles (intravenous) , Fever, chills, and asthenia following intravascular injection were more common and more severe than after intratumoral injections (grade 2-3 fever and chills vs grade 1). Dose-related transaminitis was reported infrequently. The transaminitis was typically transient (<10 days) and low-grade (grade 1-2) and was not clinically relevant. Further dose escalation was limited by supply of the virus.
Viral replication was documented at early time points after intratumoral injection in head and neck cancer patients [49, 53]. Roughly 70% of patients had evidence of replication on days 1-3 after their last treatment (Table II). In contrast, day 14-17 samples were uniformly negative. Patients with injected pancreatic tumors, in contrast, showed no evidence of viral replication by plasma PCR (indirect evidence) or fine-needle aspiration. Similarly, intraperitoneal dl1520 could not be shown to reproducibly infect ovarian carcinoma cells within the peritoneum. Therefore, different tumor types can vary dramatically in their permissiveness for viral infection and replication (Table II).
Proof-of-concept for tumor infection following intraarterial  or intravenous  administration with human adenovirus has also been achieved. Approximately half of the roughly 25 patients receiving hepatic artery infusions
Viral Replication Data from Phase I and II Trials of dl1520 (Onyx-O15): Intratumoral, Intraperitoneal, Intraarterial, or
Route of administration
Was this article helpful?
Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.