Editor's Note
	Audio for patients

In the fall of 2000, I found myself at the Miami airport waiting to board a flight to DC for the NIH Consensus Conference on Early Breast Cancer. This was my pre-cell phone era, and my beeper went off alerting me to a call I had been anxiously anticipating for weeks. Greg McIntosh, from the market research firm ReedHaldyMcIntosh, wished to speak with me.

I scrambled for a pay phone to find out about the initial report from the first formal external, independent study of our breast cancer audio series. Greg told me that the initial five interviews with medical oncologists went flawlessly, and based on this, he was confident that his team would be able to recruit and study the remaining 145 randomly selected United States-based physicians in the next few weeks. For some inexplicable reason, this situation was reminiscent of my clinical research years as a member of the University of Miami faculty, when patients would return after their first course of an experimental therapy and I would anxiously pull out x-rays (remember those?) to assess for response.

“Greg, how many of these first five docs listen to our program?” I held my breath waiting for the answer. Greg paused for a moment, checking his notes, and said, “Let’s see…1, 2, 3, 4…four of the five.” My prolonged exhalation lasted the entire five-hour air and land journey to the Holiday Inn in Bethesda. After years of wondering whether our work was having an impact, the answer was about to emerge.

Third-party continuing medical education programs supported by grants from pharmaceutical companies and distributed without charge to physicians are rarely evaluated independently. Minimal scientifically validated information exists to indicate how often physicians utilize these resources. Programs are generally considered successful if used by five to 10 percent of recipients, and as we all know, a plethora of such educational publications regularly inundate oncologists’ mailboxes.

Although it was clear that some oncologists listened to our programs, I was concerned that the “ratings” would be minuscule and that perhaps our company would go out of business. Needless to say, the decision to conduct this study was one of the greatest risks of my totally non-MBA-like business career. In one sense, the survey would differentiate our work from many other CME groups because it was an independent review. The core of our group includes clinician writers who are used to the scientific method because of prior experience with clinical research. Greg’s company was similar to the external data monitoring committees we had long dealt with in clinical trials. Of course, the other side of this slippery slope is that if our work was not being utilized, we would all need to seek other jobs.

The impetus for the decision to do the study came from Brian Moss, a former AstraZeneca marketing person on the Nolvadex^® (tamoxifen) team, who left the company to seek an MBA from Columbia. Brian consulted with our group part-time during his two years in New York and strongly recommended that we do the study, partly because he believed in the work, and partly because it was the only way to ensure fiscal security for the future. Brian would later move his family to Miami and join our group as Executive Vice President of Business Development.

The next day, at the nonmomentous and possibly last NIH breast cancer consensus conference, I was still somewhat on cloud nine. During one of the breaks, I ran into Hy Muss and Kathy Pritchard and told them about the first five “patients” in the study of our audio series. Hy quipped, “If I were looking for a 10 to 20 percent response rate in a Phase II trial, and four of the first five patients responded, I’d be pretty optimistic.” Kathy — ever the skeptic and usually the first person to the microphone to shoot holes in the data after a research presentation — talked about confidence intervals and events; however, on a deep and personal level, I knew things had changed.

By the following month, Greg and his team had discovered that almost two thirds of the oncologists in the United States were listening to our tapes. (Although the series began in 1988, CDs were not added until 2001.) We now produce nationally distributed audio series on cancer of the lung, prostate, breast, colon-rectum and, of course, NHL. Our US-based audience includes medical oncologists, radiation oncologists, surgeons, urologists and nurses. Enclosed with this medical oncologist issue of NHL Update is our first series for cancer patients and perhaps the biggest leap of faith we have taken since the 2000 market research study.

We had been thinking about producing a series for patients for a long time and have consulted endlessly with physicians, nurses and patients to determine if the concept has merit and how to optimally distribute this type of product. After much time, reflection and forethought, our hope is that we have developed a resource that will provide general background information that can supplement and reinforce the specific individualized recommendations made by a treating oncologist.

For this first issue, we utilized the successful approach of our audio series for healthcare professionals — one-on-one interviews with clinical research leaders. The initial interviews were fascinating, and I quickly learned that some researchers naturally rattle off well-thought-out explanations of diagnostic and therapeutic procedures in layperson’s terms while others persistently use language that most “normal people” would find impossible to comprehend.

The first speaker is John Leonard, who describes in detail a de-identified case from his practice, and throughout the interview, he recreates his discussions with this 55-year-old mother of one of the nurses in his hospital.

The theme of this first issue is the role of clinical research in patient care, including ongoing studies that patients may join and recently reported trials with data that are relevant in treatment decisions. John’s patient had high-risk diffuse large B-cell lymphoma, and in a remarkably understandable manner, he explains how this patient’s somewhat adverse IPI score was derived and what this meant in terms of prognosis.

He reviews R-CHOP, the standard therapy in this situation, and patiently discusses the expected side effects and toxicities associated with each agent in the regimen. He then comments on clinical research and how prior trials have moved the field forward and, in this case, defined the risks and benefits of R-CHOP in this situation.

Dr Leonard then explains the difference between chemotherapy and immune therapy, such as rituximab, and expounds on the new agents and approaches that are under active investigation, including a trial at his institution evaluating R-CHOP plus bortezomib. John then discusses this patient’s decision to enter that trial, the tumor regression that ensued and a two-day hospitalization for neutropenic fever, which occurred in spite of the use of pre-emptive growth factors.

The next speaker on the program is Mitchell Smith, who tackles mantle-cell lymphoma and presents a patient treated on a Phase II ECOG study of R-CHOP followed by radioimmunotherapy. Mitch is another physician with the rare and unique ability to make complex concepts comprehensible, and he has a kind but honest approach to discussing the threats posed by this disease.

Brad Kahl, the final researcher interviewed for the patient series, reviews the challenging topic of follicular lymphoma. Brad is the principal investigator of ECOG’s Phase III RESORT trial, which evaluates indefinite rituximab maintenance after up-front single-agent treatment compared to up-front rituximab followed by re-administration on relapse. Brad not only beautifully explains the background to this important trial and the difficult-to-comprehend concept of randomization, but also why the associated correlative science work on tissue specimens in the study is so important in helping us to better understand the effect of the monoclonal antibody rituximab on lymphoma cells.

The goal of this patient education program is to provide expert perspectives that will supplement and reinforce what patients learn from their physicians and nurses. Our next issue will take a different approach, as we will interview a number of patients with NHL and present relevant comments from research leaders.

This is somewhat of a bold new world for our CME group, but we have confidence that by using a scientific approach to evaluate this work, we will find something helpful for patients. We invite patients and healthcare professionals to listen to the enclosed CDs or to visit our website (www.NHLUpdate.com/Patients) and download the audio program without cost. The full transcript of the patient program is also available on our website and on the first audio CD.

This experiment in patient education requires careful evaluation. We are interested in knowing whether the discussions on this audio program are understandable and useful and what other topics might be of interest to patients. We are also anxious to find out how the web works as a method of distribution. We are particularly curious whether patients who are internet naïve will ask their children or grandchildren to utilize their music downloading experience to assist in obtaining our program. Feedback from all is most welcome, and we invite you to tell us what works and what needs to be fixed.

—Neil Love, MD
NLove@ResearchToPractice.net

Select publications

Ghielmini M et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 2004;103(12):4416-23. Abstract

Habermann TM et al. Rituximab-CHOP versus CHOP with or without maintenance rituximab in patients 60 years of age or older with diffuse large B-cell lymphoma (DLBCL): An update. Proc ASH 2004;Abstract 127.

Hainsworth JD et al. Maximizing therapeutic benefit of rituximab: Maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin’s lymphoma — A randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005;23(6):1088-95. Abstract

Hainsworth JD et al. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: A phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003;21(9):1746-51. Abstract

Halaas JL et al. The Follicular Lymphoma International Prognostic Index (FLIPI) is superior to WHO/REAL histological grade for identifying high-risk patients: A retrospective review of the MSKCC experience in 260 patients with follicular lymphoma. Proc ASH 2004;Abstract 3268.

Hiddemann W et al. Effect of the addition of rituximab to front line therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) on the remission rate and time to treatment failure compared to CHOP alone in mantle cell lymphoma: Results of a prospective randomized trial of the German Low Grade Lymphoma Study Group. Proc ASCO 2004;Abstract 6501.

Hochster HS et al. Results of E1496: A phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL). Proc ASCO 2004;Abstract 6502.

Marcus R et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005;105(4):1417-23. Abstract

Romaguera JE et al. Rituximab plus hypercvad (R-HCVAD) alternating with rituximab plus high-dose methotrexate-cytarabine (R-M/A) in untreated mantle cell lymphoma (MCL): Prolonged follow-up confirms high rates of failure-free survival (FFS) and overall survival (OS). Proc ASH 2004;Abstract 128.

van Oers MH et al. Chimeric anti-CD20 monoclonal antibody (rituximab; Mabthera®) in remission induction and maintenance treatment of relapsed/resistant follicular non-Hodgkin’s lymphoma: A phase III randomized Intergroup clinical trial. Proc ASH 2004;Abstract 586.