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WESTPORT, Aug 01 (Reuters Health) - A phase II trial of gene therapy combined with chemotherapy has shown that the treatment is more effective than either regimen alone in patients with recurrent head and neck cancers, according to a multinational team of researchers.
The ONYX-015 adenovirus lacking the E1B 55-kDa gene selectively kills p53-deficient cancer cells, but produces clinical benefit in only about 15% of patients with recurrent, refractory cancers of the head and neck, according to Dr. Fadlo R. Khuri, of the University of Texas M. D. Anderson Cancer Center, in Houston, and colleagues. Disease also rapidly recurs with chemotherapy alone.
To see if gene therapy might be more effective in combination with chemotherapy, the researchers administered ONYX-015 intratumorally in combination with cisplatin and 5-fluorouracil in 37 patients. In patients with more than one tumor mass, only the largest mass was injected with the virus.
In the August issue of Nature Medicine, they report that the tumors shrank in 25 of the 30 cases that could be evaluated for treatment efficacy, which included 8 complete and 11 partial responses. Six months after treatment, only 17% of injected tumors had progressed. In patients with multiple tumor masses, most of the injected tumors responded, while most of the uninjected tumors did not. The median survival time was 10.5 months.
Dr. Khuri and colleagues note that "there was no correlation between response and baseline tumor size, baseline neutralizing antibody titer, p53 gene status or prior treatment."
In addition, the combined therapy was well tolerated, did not cause significant toxicity, and biopsies showed that viral replication and necrosis were specific to tumor tissue.
"Thus, ONYX-015 combined with cisplatin and 5-fluorouracil was active as a method of local control in most patients," Dr. Khuri's group writes. "Whether this enhanced local control will be translated into a survival advantage remains to be confirmed by phase III trials."
In an accompanying editorial, Dr. W. French Anderson, of the University of Southern California Keck School of Medicine, in Los Angeles, notes that it is "ironic" that the first anti-cancer clinical success of gene therapy has come from an approach that does not carry a "therapeutic" gene. "So with all its twists and turns, gene therapy seems to be turning the corner after a very bad year," he writes.
Nat Med 2000;6:862-863,879-885.
-Westport Newsroom 203 319 2700
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