Formal discussant of the trial, Robert Glynne-Jones, MD, Mount Vernon Centre for Cancer Treatment, London, said: “It is arduous to perform rectal cancer trials. That is one of reason we are interested in short endpoints.”
Regarding the first study, he said that historically, compliance has been poor with adjuvant therapy in this setting, but that the German R04 investigators achieved a high compliance. “This is an excellent rate of compliance and it should impact outcomes.” He also said that pathologic complete response is not an appropriate outcome to measure in a phase III trial.
“The message from this trial is that we need to review our assumptions regarding oxaliplatin as a radiosensitizer when it is used in only four doses. Oxaliplatin should be given with optimized fluoropyrimidine,” he said.
Dr. Glynne-Jones also said that current imaging methods overstage stage III rectal cancer. “If most patients are really stage II, we have to question a benefit for oxaliplatin. We need more accurate clinical staging in clinical trials to have more meaningful results.”
Regarding the study reported by Dr. Hofheinz, Dr. Glynne-Jones said that he was uncomfortable with the control arm, with infusional 5-FU given for 2 weeks followed by bolus 5-FU. “This control arm is a problem,” he said. Infusional 5-FU should be the standard.
He found the MARGIT investigators’ finding of an association between the development of hand-foot syndrome and improved disease-free and overall survival “intriguing.” ■
Financial Disclosure: Dr. Glynne-Jones has received research funding from Roche.