June 8, 2011 — Patients who wait to begin adjuvant chemotherapy (AC) after colorectal cancer resection have worse survival than patients who start chemotherapy earlier, according to results from a meta-analysis of 15,410 Canadian patients.
The study appears in the June issue of JAMA but was also published online June 4 to coincide with its presentation at this year's meeting of the American Society of Clinical Oncology.
"[AC] improves survival among patients with resected colorectal cancer," write James Biagi, MD, from Queen's University, Kingston, Ontario, Canada, and colleagues. "However, the optimal timing from surgery to initiation of AC is unknown."
To find out more about how timing of AC initiation affects progression of the disease, Dr. Biagi and his team conducted a meta-analysis, including only studies in which, in their view, relevant prognostic factors were adequately described. Another requirement for inclusion was that the study groups that were compared had to be fairly balanced, or else the results had to have been adequately adjusted for any lack of balance.
The investigators identified 10 previously conducted studies. Nine were population- or cohort-based studies; 1 was a secondary analysis that was part of a larger randomized clinical trial.
On the basis of the data from the 10 studies, the authors found that relative overall survival decreased by 14% for every 4-week delay before initiation of AC.
One inherent limitation is the effet of the patient’s postsurgical performance on time to AC. Other study design flaws include the use of retrospective, nonrandomized data; the lack of knowledge of completion rates for AC; and the assumption of linearity when extrapolating data in 4-week intervals. In addition, the results of this meta-analysis are largely based on the fluoropyrimidine era; it is unclear whether the data would still apply now, during the oxliplatin era.
"Applying our findings to a patient who is ready to initiate AC 4 weeks after surgery but is delayed because of logistical rather than medical reasons, that same patient would have a 14% increased risk of mortality if treated at 8 weeks and 30% increased risk at 12 weeks," the researchers write.
However, even if chemotherapy has to be delayed, patients may still benefit, they noted. Overall survival at 5 years without chemotherapy is approximately 45%, but with AC survival it increases to about 60%, they said.
"Our results indicated survival of 48% if chemotherapy is administered at 12 weeks instead of 4 weeks, suggesting there may be some benefit to chemotherapy beyond a 12-week window," the authors write, noting that a reasonable time limit for initiation of AC may be more on the order of 4 to 5 months.
"Our results provide further validation of the intuitive concept of early time to AC," the authors note. "Physicians may need to more carefully consider timing when discussing AC with patients."
The study was supported in part by a grant from the Canadian Institutes of Health Research One author reported that he provided expert testimony on the relationship between delays in postlumpectomy radiotherapy for breast cancer and the probability of local control in a class action suit in Quebec in 2009. The other authors have disclosed no relevant financial relationships.
JAMA. 2011;305:2335-2342. Full text
The study appears in the June issue of JAMA but was also published online June 4 to coincide with its presentation at this year's meeting of the American Society of Clinical Oncology.
"[AC] improves survival among patients with resected colorectal cancer," write James Biagi, MD, from Queen's University, Kingston, Ontario, Canada, and colleagues. "However, the optimal timing from surgery to initiation of AC is unknown."
To find out more about how timing of AC initiation affects progression of the disease, Dr. Biagi and his team conducted a meta-analysis, including only studies in which, in their view, relevant prognostic factors were adequately described. Another requirement for inclusion was that the study groups that were compared had to be fairly balanced, or else the results had to have been adequately adjusted for any lack of balance.
The investigators identified 10 previously conducted studies. Nine were population- or cohort-based studies; 1 was a secondary analysis that was part of a larger randomized clinical trial.
On the basis of the data from the 10 studies, the authors found that relative overall survival decreased by 14% for every 4-week delay before initiation of AC.
One inherent limitation is the effet of the patient’s postsurgical performance on time to AC. Other study design flaws include the use of retrospective, nonrandomized data; the lack of knowledge of completion rates for AC; and the assumption of linearity when extrapolating data in 4-week intervals. In addition, the results of this meta-analysis are largely based on the fluoropyrimidine era; it is unclear whether the data would still apply now, during the oxliplatin era.
"Applying our findings to a patient who is ready to initiate AC 4 weeks after surgery but is delayed because of logistical rather than medical reasons, that same patient would have a 14% increased risk of mortality if treated at 8 weeks and 30% increased risk at 12 weeks," the researchers write.
However, even if chemotherapy has to be delayed, patients may still benefit, they noted. Overall survival at 5 years without chemotherapy is approximately 45%, but with AC survival it increases to about 60%, they said.
"Our results indicated survival of 48% if chemotherapy is administered at 12 weeks instead of 4 weeks, suggesting there may be some benefit to chemotherapy beyond a 12-week window," the authors write, noting that a reasonable time limit for initiation of AC may be more on the order of 4 to 5 months.
"Our results provide further validation of the intuitive concept of early time to AC," the authors note. "Physicians may need to more carefully consider timing when discussing AC with patients."
The study was supported in part by a grant from the Canadian Institutes of Health Research One author reported that he provided expert testimony on the relationship between delays in postlumpectomy radiotherapy for breast cancer and the probability of local control in a class action suit in Quebec in 2009. The other authors have disclosed no relevant financial relationships.
JAMA. 2011;305:2335-2342. Full text
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου