May 31, 2009 (Orlando, Florida) — Adding oxaliplatin (Eloxatin) to standard preoperative radiochemotherapy in patients with locally advanced rectal cancer does not improve tumor shrinkage, according to study results presented here at the American Society of Clinical Oncology (ASCO) 45th Annual Meeting.
However, an exploratory analysis illuminated a possible bright spot in the data — that adding oxaliplatin might reduce the number of distant metastases, said the study's lead author, Carlo Aschele, MD, PhD, from the E.O. Ospedali Galliera in Genoa, Italy.
"The data do not support the use of oxaliplatin with the goal of shrinking tumors," said Dr. Aschele. However, further study on the drug's effect on metastases is ongoing and worthwhile. "Stay tuned," he added.
Dr. Aschele also acknowledged that oxaliplatin significantly increased toxicity in patients, compared with the single-agent standard, 5-fluorouracil (FU).
Oxaliplatin, a chemotherapy that sensitizes tumors to radiation, was added to standard treatment in the hope that it would improve the rate at which tumors shrink and completely disappear, or complete pathological response, explained expert Jennifer Obel, MD.
Dr. Obel was not involved in the trial but is a member of the ASCO Cancer Communications Committee. She is gastrointestinal oncologist at the NorthShore University HealthSystem in Evanston, Illinois.
Dr. Obel encouraged clinicians not to immediately dismiss this approach and study based on the findings about complete pathological response.
"Is this a negative outcome? No. This early result does not necessarily mean that there will be a negative result in the long run," she said, explaining that the study has not yet provided data on overall survival, which is the primary outcome.
However, she also acknowledged that, in other studies, patients with complete pathological response have been shown to have better outcomes than those patients without the response.
Equally High Rates of Patients Eventually Undergo Surgery
In the trial, 747 patients with locally advanced rectal cancer were randomized to receive standard preoperative chemoradiotherapy or the standard plus oxaliplatin. Patients were randomized to a regimen of infused FU (225 mg/msq per day) concomitant to external-beam pelvic radiation (50.4 Gy in 28 daily fractions), or to the same regimen plus weekly oxaliplatin (60 mg/msq × 6). Surgery was scheduled 6 to 8 weeks after initial therapy was completed.
There was no significant difference between the 2 groups in terms of preoperative tumor reduction; 16% of patients in both groups had no tumor present at the time of surgery, and 29% in the oxaliplatin group had mildly invasive tumors (T1 or T2) without nodal involvement (vs 30% in the control group).
There was also no significant difference in the number of patients who had cancer in the lymph nodes (27% in the oxaliplatin group and 25% in the control group).
In an unplanned analysis, Dr. Aschele and colleagues found that, at the time of surgical removal of the primary tumor, only 0.5% of the oxaliplatin group (2 patients) had distant metastases in the abdomen, compared with 3% in the control group (11 patients). The difference was statistically significant.
"We believe these data are plausible," said Dr. Aschele, conceding that the numbers were small.
Adding oxaliplatin also resulted in significantly increased adverse effects, said Dr. Aschele. Overall, grade 3 or 4 toxicity rates in treated patients were 8% in the control group and 24% in the oxaliplatin group (P < .001).
Despite this lopsided difference in adverse events, 96% of patients in both groups eventually underwent surgery, Dr. Aschele pointed out. "More aggressive chemotherapy did not negatively affect who underwent surgery," he noted.
The researchers have disclosed no relevant financial relationships.
American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract CRA4008. Presented May 30, 2009. Abstract
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