NEW YORK (Reuters Health) May 30 - Adding oxaliplatin to preoperative chemoradiation for rectal cancer doesn't improve tumor response, but it does increase toxicity, a new phase III study shows.
"The addition of another agent isn't making any progress for us," Dr. Martin R. Weiser of Memorial Sloan-Kettering Cancer Center in New York City, told Reuters Health. He wrote an editorial accompanying a report of the study in the Journal of Clinical Oncology, online May 23.
Fluorouracil plus radiation is an effective pre-surgery treatment for locally advanced colon cancer, but it doesn't reduce distant metastases in these patients, Dr. Carlo Aschele of Istituto Nazionale per la Ricerca sul Cancro in Genoa, Italy, and colleagues explain in their report.
Given that oxaliplatin combined with fluorouracil is an effective adjuvant treatment for some colon cancer patients, and has shown promise as a palliative for metastatic disease, investigators had hoped that it might control distant micrometastases in rectal surgery patients by increasing tumor radiosensitivity.
They randomly assigned 747 patients with locally advanced, resectable rectal cancer to pelvic radiation and infused fluorouracil with or without oxaliplatin before surgery. Overall survival was the primary endpoint.
In response to the presurgery treatment, 24% of patients given oxaliplatin had grade 3 to grade 4 adverse events, compared to 8% of patients who didn't receive oxaliplatin.
The pathological complete response rate was 16% in both groups. Rates of positive lymph nodes, tumor spread beyond the muscularis propria, and positive circumferential resection margins were also similar in both groups.
In the control group, 2.9% had intra-abdominal metastases, compared to 0.5% in the treatment group - a nonsignificant difference.
While compliance was lower among patients given oxaliplatin, Dr. Aschele and his colleagues write, it's unlikely to account for the lack of effectiveness in the treatment arm, given that 80% of oxaliplatin patients had at least five administrations of the therapy, and more than 90% received at least 45 Gy of radiation.
"The most likely explanation for the current results is therefore that, despite the preclinical rationale and promising phase II data, oxaliplatin isn't a clinically effective radiation sensitizer, at least using the dose and regimen as prescribed in this report," Dr. Aschele and his team conclude.
In his editorial, Dr. Weiser points out, "These were very expensive trials and in essence all will show the same thing. Isn't there possibly a better way to do this? I think that's what most people are feeling."
"The tortured pace of trials, the absence of promising ideas, and the failure of adding agents to current treatment algorithms lead to the conclusion that, rather than business as usual, we need to begin to individualize care," he writes. "Intensify treatment for those tumors demonstrating aggressive biology and limit treatment for those with more favorable biology."
"Instead of just throwing more drugs at things and adding more drugs, we're going to try to start pulling things away and see if we can do as well. The new movement will be toward individual care."
"The addition of another agent isn't making any progress for us," Dr. Martin R. Weiser of Memorial Sloan-Kettering Cancer Center in New York City, told Reuters Health. He wrote an editorial accompanying a report of the study in the Journal of Clinical Oncology, online May 23.
Fluorouracil plus radiation is an effective pre-surgery treatment for locally advanced colon cancer, but it doesn't reduce distant metastases in these patients, Dr. Carlo Aschele of Istituto Nazionale per la Ricerca sul Cancro in Genoa, Italy, and colleagues explain in their report.
Given that oxaliplatin combined with fluorouracil is an effective adjuvant treatment for some colon cancer patients, and has shown promise as a palliative for metastatic disease, investigators had hoped that it might control distant micrometastases in rectal surgery patients by increasing tumor radiosensitivity.
They randomly assigned 747 patients with locally advanced, resectable rectal cancer to pelvic radiation and infused fluorouracil with or without oxaliplatin before surgery. Overall survival was the primary endpoint.
In response to the presurgery treatment, 24% of patients given oxaliplatin had grade 3 to grade 4 adverse events, compared to 8% of patients who didn't receive oxaliplatin.
The pathological complete response rate was 16% in both groups. Rates of positive lymph nodes, tumor spread beyond the muscularis propria, and positive circumferential resection margins were also similar in both groups.
In the control group, 2.9% had intra-abdominal metastases, compared to 0.5% in the treatment group - a nonsignificant difference.
While compliance was lower among patients given oxaliplatin, Dr. Aschele and his colleagues write, it's unlikely to account for the lack of effectiveness in the treatment arm, given that 80% of oxaliplatin patients had at least five administrations of the therapy, and more than 90% received at least 45 Gy of radiation.
"The most likely explanation for the current results is therefore that, despite the preclinical rationale and promising phase II data, oxaliplatin isn't a clinically effective radiation sensitizer, at least using the dose and regimen as prescribed in this report," Dr. Aschele and his team conclude.
In his editorial, Dr. Weiser points out, "These were very expensive trials and in essence all will show the same thing. Isn't there possibly a better way to do this? I think that's what most people are feeling."
"The tortured pace of trials, the absence of promising ideas, and the failure of adding agents to current treatment algorithms lead to the conclusion that, rather than business as usual, we need to begin to individualize care," he writes. "Intensify treatment for those tumors demonstrating aggressive biology and limit treatment for those with more favorable biology."
"Instead of just throwing more drugs at things and adding more drugs, we're going to try to start pulling things away and see if we can do as well. The new movement will be toward individual care."
1 σχόλιο:
Thanks for posting this.
Δημοσίευση σχολίου