Select Excerpts from the Interview

CD 2, Track 12

DR LOVE: Would you provide an overview of the Mabthera International Trial (MInT) and some of the trials for patients who relapse?

DR YOUNES: MInT was spearheaded by Michael Pfreundschuh from Germany (Pfreundschuh 2004a, 2004b). It was truly an international trial because it included investigators from Europe, Asia and South America. The trial specifically looked at the role of rituximab in combination with chemotherapy. The specific regimen was chosen by the investigator, and approximately 50 percent of the investigators used CHOP, while others — particularly in Germany — used a CHOP equivalent such as CHOEP.

MInT confirmed, in a randomized fashion, that the addition of rituximab to CHOP or CHOP-like regimens improves outcomes specifically in terms of complete remission rate and survival in patients who are younger than 60 years of age (3.1).

Trials have also been conducted for patients with relapsed disease. One trial from Memorial Sloan-Kettering reported on the use of rituximab with isofosfamide/carboplatin/etoposide (ICE) chemotherapy (Kewalramani 2004). This was not a randomized trial; it was a Phase II trial, but it compared data with previous experience using ICE chemotherapy — sequential trials from the same institution using similar eligibility criteria. They showed that the addition of rituximab to salvage therapy like ICE improves the complete remission rate.

Improving complete remission rate prior to transplant is a very important prognostic factor, because patients who receive transplant during complete remission have a better outcome and survival than patients who are not in complete remission at the time of transplantation.

We had similar outcomes in our institution using a regimen of paclitaxel, topotecan and rituximab (TTR). We utilized the regimen for patients with diffuse large B-cell lymphoma who failed to respond to front-line regimens — they were treated with TTR at first or second relapse. We’ve seen a similar improvement in overall response rate and an improvement in complete remission rate, making these patients better candidates for stem cell transplantation.

CD 2, Track 13

DR LOVE: What are your thoughts about dose-dense chemotherapy in patients with lymphoma?

DR YOUNES: Dose-dense therapy is an important concept that is now gaining some appeal, especially for solid tumors. In non-Hodgkin’s lymphoma, Michael Pfreundschuh spearheaded a randomized trial — published in Blood — that compared CHOP-14 and CHOP-21 with or without etoposide (Pfreundschuh 2004c, 2004d). The interesting thing about the data was — at least in the elderly patients — the dose-dense 14-day regimen was superior to the 21-day regimen (3.2). However, these trials were conducted before the incorporation of rituximab, so we don’t know if R-CHOP-14 is superior to R-CHOP-21. Currently, randomized trials are investigating this question, but we don’t know the results yet.

DR LOVE: At this time, do you think it’s rational to utilize R-CHOP-14 in the clinical setting, particularly in patients with poor prognostic factors?

DR YOUNES: I don’t think it’s wrong to use R-CHOP-14 in selected patient populations, simply because it’s not more toxic, at least based on the Pfreundschuh data. We would not be harming patients, but whether or not it’s more beneficial is yet to be determined in a randomized study.

CD 2, Track 17

DR LOVE: Would you discuss your approach to patients with follicular lymphoma who present for first-line therapy?

DR YOUNES: It’s complicated, particularly when you discuss these issues with the increasing number of educated patients. They’re aware of what’s available — a large menu of options that are all reasonable. But the majority of trials never made head-to-head comparisons to determine whether one treatment is better than the other, and that’s creating confusion for the patients. We know right now that when you add rituximab to a front-line regimen for patients with advanced-stage follicular lymphoma, you improve outcomes in terms of duration of remission and the percentage of patients whose disease enters remission. Most oncologists believe this will eventually translate into improved survival.

What’s the optimal combination — chemotherapy with rituximab? No one knows. A large menu of combination chemotherapy regimens is available that you can combine with rituximab, or you can use rituximab alone. Furthermore, information is emerging about the use of radioimmunotherapy up front — at least in the experimental setting — that can demonstrate effectiveness perhaps as good as combination chemotherapy but with shortened duration of treatment and potentially fewer potential side effects (Kaminski 2005).

I am pro-clinical trial participation. Although I discuss the different options that may be used off protocol, I tend to encourage patients to participate in the clinical trials. Outside clinical trials, I use one of three combinations, depending on the patient’s situation and preference. It’s a mutually agreeable treatment plan. I tend to use R-CHOP, R-FND or R-CVP. I extensively discuss the pros and cons of these regimens with the patients and their families, and then we reach a mutual agreement. I think the majority of oncologists in North America use R-CHOP or R-CVP for patients with advancedstage follicular lymphoma.

Select publications