Although all of this extensive research activity involving new biologic agents for advanced melanoma may look promising, a cautionary note was sounded by Dr. Mark R. Middleton of Cancer UK and the University of Oxford (England), who has witnessed a relentless succession of therapeutic disappointments on the melanoma front during his career in medical oncology.
"In melanoma we already have a wealth of therapeutic options. Untold numbers of drugs have been tested in our patients. Unfortunately, none of them work particularly well. The response rates are pretty dismal compared to those for most other solid tumors," Dr. Middleton observed.
Indeed, numerous combinations of chemotherapeutic agents or chemotherapy drugs and biologicsmainly interferons and interleukinshave been tested over the last 20 years. What these combinations have had in common was a weak therapeutic rationale and impressively high tumor response rates in mostly single-center phase II trials, which failed to translate into any overall survival advantage over DTIC alone in phase III studies.
"It's not that anybody's playing games with their phase-IIs, but naturally with combination regimens that you're trying for the first time you're going to enroll better, fitter patients and overestimate what you can get out of it, particularly if you're using historical controls," he explained.
"I think the definition of promising clinical activity has to be based on survival rather than response rates because we've clearly been caught out by the combination chemotherapy and biochemotherapy stories. It's very, very clear from that experience that the higher response rates haven't translated into survival improvements," Dr. Middleton added.
Dr. Middleton and Dr. Eggermont have received research funding from and are consultants to Schering-Plough.
In addition, Dr. Eggermont is a consultant to Bayer, Boehringer Ingelheim, GlaxoSmithKline, Sanofi Pasteur, Onyx Pharmaceuticals, Genta Inc., and Synta Pharmaceuticals. Dr. Lebbé has received research funding from Novartis.
"The definition of promising clinical activity has to be based on survival rather than response," said Dr. Mark R. Middleton. Bruce Jancin/Elsevier Global Medical News