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Adding injections of an engineered adenovirus to chemotherapy roughly doubled the proportion of head and neck or oesophageal cancers that shrank, but the trial reported no survival figures.
Phase 3 randomised trial of intratumoural H101, an E1B-55 kilodalton gene-deleted replication-selective adenovirus of essentially the same design as ONYX-015, added to cisplatin-based chemotherapy in squamous cell cancer of the head and neck or oesophagus. 160 patients were recruited. Patients with no history of, or sensitivity to, cisplatin and fluorouracil received that regimen; those who had not responded to it received doxorubicin and fluorouracil. Each group was randomised to receive intratumoural H101, at 5.0 x 10^11 to 1.5 x 10^12 viral particles per day for five consecutive days every three weeks, or not.
Among 123 evaluable patients, overall response rate with cisplatin and fluorouracil plus H101 was 78.8 per cent (41 of 52) against 39.6 per cent (21 of 53) for that chemotherapy alone. The differences between the combined virus arms and the chemotherapy-alone arms were significant. The main side effects were fever in 45.7 per cent, injection-site reaction in 28.3 per cent and influenza-like symptoms in 9.8 per cent. H101 was approved in China in 2005 and marketed as Oncorine, making it the first oncolytic virus approved anywhere.
The world's first approval of an oncolytic virus rests on a response-rate trial of 160 patients with no survival endpoint, an uneven randomisation across two chemotherapy backbones, and 37 patients excluded from the efficacy analysis. Tumour shrinkage after injecting something into a tumour is the easiest result to obtain in this field and the least informative. H101 has never been approved outside China.