In Reply
Authors: Oliver W. Press, Richard I. Fisher
Journal: Journal of Clinical Oncology (2007)

assigned to an interferon or observation arm.There was no significant difference in responses after either induction program.Overall survival and failure-free survival were similar between both arms after 38 months of follow-up.It was concluded that epirubicin did not add any benefit to this cohort of patients. 9Only two studies suggested improved outcome in FL patients when treated with CHOP-R.The first was a small phase II trial from a single institution that reported on 38 patients and suggested sustained responses at 9 years of follow-up. 10 Although the follow-up is impressive, nonetheless, this was a phase II nonrandomized trial with a limited number of patients that would make it difficult to suggest CHOP-R as the standard of care in frontline therapy of FL.In addition, it was not clear whether all patients enrolled onto this phase II study met the National Cancer Institute criteria to initiate therapy.The second study was reported by Hiddemann et al, 3 who randomly assigned more than 400 patients to CHOP or CHOP-R and noted improved outcomes in the CHOP-R arm.However, this study assumed that CHOP would be the standard therapy in FL, rather than cyclophosphamide, vincristine, and prednisone (CVP) or other nonanthracycline-based regimens.The authors did not offer a clear and convincing explanation as to how that choice was made.Second, the anthracycline approach, if adapted as a front-line therapy for FLs, might have an adverse impact on patients, especially if treatment takes place at a younger patient age.Cardiac toxicity is a well-established risk factor that can occur at much later stages in life. 11Myelodysplasia is also a possible complication of anthracycline-based therapy that has been reported by several investigators. 12,13 Last, it is always difficult to decide on the best control arm when designing clinical trials, but making this choice based on nonrandomized data (between anthracycline and nonanthracycline type regimens) would unfairly justify incorporating a rather aggressive and arguably unnecessary approach in individuals with low-grade disease.Are we conveying a message to oncologists that CHOP is the correct chemotherapeutic choice for FL, and that the question now lies in determining whether "cold" or "hot" antibody-type of an approach provides better outcome when combined with CHOP?I would argue that CHOP should be reserved for FL patients who are either in transformation or whose disease is behaving aggressively.Alternative options are used more often such as CVP and fludarabine-containing regimens, novantrone, and dexamethasone (FND).I propose that we pause and evaluate how we design large phase III randomized studies carefully.The current Intergroup trial is having difficulty accruing patients.The principal investigators of this study are understandably appealing to community oncologists to accrue to this trial; however, it would have been prudent to understand how community oncology (that treats more than 80% of cancer patients) approaches FL.In the absence of solid data to support the utilization of anthracyclines in FL patients, I suspect that this study will take much longer time than anticipated to accrue, but in my opinion this lag is for a few good reasons as I have outlined.