|
You are here: Home: Meet The Professors Vol. 3 Issue 1 2005: Editor's Office
 |
Editor’s Note  |
| Watch and worry |
In low grade lymphoma, the basis for the “watch and wait” approach is that the disease is considered incurable. First, we need to clarify that the lack of curability holds mostly for Stage IV presentations, which are the majority of cases. Second, the other rationale is that if you cannot cure the disease and you don’t need to palliate anything because the patient is asymptomatic, why treat early?
I’m going to say something controversial and no one is going to believe it, but data from the various studies we did over the last 25 years at MD Anderson indicate a plateau in the curve for low grade lymphomas, and that plateau has been increasing through the years as we modified the regimens.
The plateau occurs at approximately eight years, and at 15 years, 40 percent of the patients are alive without evidence of disease. I think people have not realized that there is a plateau, mostly because they’ve been using single agents or palliative types of therapy, but also because they haven’t followed the patients long enough. If you stop your observation period at five to 10 years, you fail to see that the tail end of the curve plateaus.
I believe that if you treat Stage IV low grade lymphoma appropriately, you can cure a fraction of the patients — not necessarily the majority — but more or less about the same that you cure with large cell lymphoma. Sandy Horning has a slide she shows that indicates that the survival of low grade lymphoma has not changed for 20 years, which is true at Stanford. But they’ve been doing the same thing over and over again. Why would you expect to see a change? We’ve been changing the regimens every four to five years. When I evaluated our data, I was surprised that we are now seeing a definite plateau in the curve.
— Fernando Cabanillas, MD |
 |
Upon meeting Fernando Cabanillas just prior to the audio recording session for this program, I immediately thought of my childhood hero, Sigmund Freud. Like Dr F, Dr C enjoys challenging long-held paradigms, as evidenced by the above comment.
As in our prior Meet The Professors adventures, I had gathered a group of very astute, regionally based medical oncologists to present de-identified cases from their practices to our learned faculty of Fernando, John Hainsworth, John Leonard and Mitchell Smith.
Many of the metropolitan NYC-based community docs at this meeting had worked with us on our prior breast cancer MTPs and knew the drill. As in the past, these docs more than did their jobs by identifying a variety of vexing clinical situations with no perfect solutions but plenty to fuel lively debate.
Many of the cases discussed were indolent lymphoma, for which patients with asymptomatic disease now have a relatively nontoxic alternative (rituximab) to observation. Prior to the emergence of this fascinating monoclonal antibody, the perception that survival is not improved with earlier therapy meant that chemotherapy only offered asymptomatic patients the option of side effects and perhaps the psychological comfort of taking an active step against a known cancer. Both researchers and practitioners agree that before rituximab, the logical but highly unrealistic strategy of “watch and wait” — as in other tumors, including prostate cancer — was seriously problematic. Community panelist Dr Charles Farber calls it “watch and worry.”
Both the faculty and community docs agreed that it is important in this situation to carefully clarify whether the patient is truly asymptomatic. This can be challenging in an era when a symptom such as fatigue might also be the result of stress, sleeplessness or lack of exercise. John Hainsworth suggests a practical assessment of whether the patient’s activity level has changed. In the case that sparked Dr C’s bombshell comment, an avid golfer was incidentally diagnosed with Stage IV low grade lymphoma during arthroscopy. A related question would be whether the patient’s frequency of hitting the links had decreased.
If Dr Cabanillas’s assertion is true, and eradication of clinical disease is possible, then this is a semi-moot point. Dr Hainsworth and others are not nearly as convinced that this is the case, but patients and physicians should be informed that at least some experienced research leaders believe early therapy with rituximab plus chemotherapy might eradicate the disease in a significant number of patients.
Sometimes it seems that we are carrying the torch of evidence-based medicine a bit too far. We will never have large randomized trials to address every possible clinical question in oncology. As noted by onco-provocateur, Barry Kaplan, in indolent lymphoma, by the time a trial’s survival endpoint is met, the principal investigator is likely to be retired or dead. The search for intermediary endpoints to predict survival may change this someday, but currently we must rely on experienced, thoughtful, unbiased mavens like our faculty to lead the way.
I love to see people stick out their necks and challenge existing dogma. Usually this is some variation on the obvious, and Dr Cabanillas’ postulation on the potential curability of indolent NHL is not more difficult to believe than Dr Freud’s notion that our thoughts and behaviors are expressions of a much more complex maelstrom beneath the surface.
Perhaps at some point in our lifetimes, another free thinker will simplify the mysteries of NHL and other tumors, but for the moment, patients and their physicians will struggle with painful decisions that are often based on evidence that may not totally clarify the best path to take in many common oncologic situations.
—Neil Love, MD
NLove@ResearchToPractice.net
Fisher RI et al. New treatment options have changed the natural history of follicular lymphoma. Blood 2004;104(11);Abstract 583.
Ha CS et al. Stage III follicular lymphoma: Long term follow-up and patterns of failure. Int J Radiat Oncl Biol Phys 2003;57(3):748-54. Abstract
Horning SJ. Natural history of and therapy for the indolent non-Hodgkin’s lymphomas. Semin Oncol 1993;20(5 Suppl 5):29-34. No abstract available
Seymour JF et al. Long-term follow-up of a prospective study of combined modality for stage I-II indolent non-Hodgkin’s lymphoma. J Clin Oncol 2003;21(11):2215-22. Abstract
|
|
