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Eric Rosenthal Reports | A Personal Remembrance of Two Giants of Oncology: Jim and Jimmie Holland

James F. Holland, MD, one of the pioneers of combination chemotherapy and cancer cooperative group research, died at the age of 92 on March 22.  His wife, Jimmie C. Holland, MD, who was considered the founder of psycho-oncology, predeceased him by three months on Christmas Eve at age 89.

Jim was Distinguished Professor of Neoplastic Diseases at the Icahn School of Medicine at Mount Sinai in New York, and Jimmie was Wayne E. Chapman Chair in Psychiatric Oncology and attending psychiatrist at Memorial Sloan Kettering Cancer Center.

Photo 1.0: In the 1950s James (Jim) F. Holland and colleagues were considered the  “cowboys” of chemotherpy.

I knew both Jim and Jimmie, had interviewed them individually numerous times over many years, and considered them friends.  They both continued to work and contribute to their fields until the end, and always had new and interesting information to share.

I first met Jimmie in 1990 when I was chairing a meeting of a group I had founded, the NCI-Designated Cancer Centers Public Affairs Network, at MSKCC and our steering committee was treated to attending grand rounds with Jimmie Holland.  Several years later I was introduced to Jim.

At dinner a few years ago hosted by Stand Up To Cancer in honor of the PBS documentary series, “Ken Burns Presents Cancer: The Emperor of All Maladies,” Jimmie and I sat together and chatted most of the evening.  Later on, I thanked Jim for lending me Jimmie as my girlfriend. “As long as you’re not her boyfriend,” he responded with the wit and good humor that characterized him almost as much as his outspoken manner and colorful neckties.

When I began writing a series last year for MedPage Today about pioneers in oncology, my first call for an interview was to Jimmie, who had been encouraging me for many years to write a book about the cultural or social history of cancer.  She had promised to write the preface.

For the MedPage series I told her that I wanted to arrange separate interviews with her and then Jim over the next few weeks.

She replied that she thought it wise to start with Jim because of several health issues he’d been dealing with, and I took her advice.

A few months following publication of Jim’s profile, I called Jimmie again about scheduling a time to talk.   She did not respond immediately and finally replied that I should contact her again in several weeks.

When we spoke, she said that she had recently undergone surgery after developing a bilateral femoral arterial emboli, and how the experience—one of the few medical issues she had encountered during her long life–had enhanced her understanding of how so many of her cancer patients had felt.  She was, after all, the psychiatrist who had pioneered a field based on how people cope with a devastating disease rather than dealing with mental illness.

Our conversation, however, only lasted a short time since she was fatigued from her condition, so we rescheduled for November when she was up to speaking at length and about some things she had never discussed before.

That interview, which may have been her last, was published a month before she died in her Revolutionary-era home in Scarsdale, NY, surrounded by her family.

I wrote to Jim expressing my condolences but did not receive a reply.  Then in March during an interview with Larry Norton, MD, who considered Jim a mentor and was a longtime colleague of Jimmie’s at Memorial Sloan Kettering, we discussed how Jim was following the loss of Jimmie.  Larry said he had written to Jim several times but hadn’t heard back.  That conversation was days before learning about Jim’s death at home from respiratory failure.

During their early years in Buffalo, N.Y., during the 1950s, Jim was chief of medicine B at Roswell Park Cancer Institute, and Jimmie was head of psychiatry at Erie County Medical Center. During an 8-year period she also had five children taking 6-month leaves between births, while pursuing her professional career.

Jimmie would relate how she had spent many evenings listening to her husband and his colleagues discuss the early development of chemotherapy and how it was making a real difference in pediatric acute lymphoblastic leukemia.

Those colleagues included Emil “Tom” Frei III, MD, with whom Jim Holland co-founded the Cancer and Leukemia Group B (CALGB). The two went on to share the Lasker Award in 1972 with Emil J. Freireich, MD, and Donald Pinkel, MD.

 Jimmie said:  “It was an exciting time in chemotherapy with new drugs coming down the pike, and I’d asked them if they asked their patients how they felt about their cancer, which helped develop my interest in issues relating to the psychological care and support of patients facing catastrophic diseases.”

She added, however, that in those days medical oncologists were not paying much attention to their patients’ quality of life since they were too engaged in the big problem of finding cures.

“They thought my concerns were just temporary stopgaps,” she said. “But I was around when we saw the first Hodgkin’s survivors. In the 1960s, we suddenly began to see people surviving.”

She said that she persuaded her husband who was a co-founder and then-head of CALGB to start a psychiatry committee that enabled the fledgling field of psychosocial oncology to add quality-of-life questions into larger protocols, providing more of a scientific basis to what was perceived as a “soft” science.

In addition to cancer-related social events I usually spent time with the Hollands at the American Association for Cancer Research (AACR) and American Society of Clinical Oncology (ASCO) annual meetings.  Jim had served as president of both organizations, and every time I saw him, his inevitable reply to my, “How are you?” was always, “Still vertical, unlike many of my colleagues.”

I will sorely miss hearing that response at AACR later this month but know that Jim and Jimmie both led long, fruitful lives that had saved the lives and soothed the psyches and emotions of countless cancer patients and their loved ones.

This article part in a series of the revival of Eric Rosenthal Reports published in Onco’Zine and formerly featured in Oncology Times.

Last Editorial Review: April 3, 2018

First published in Onco’Zine on April 3, 2018

Featured Image: Laboratory glassware containing. Courtesy: © 2010 – 2018 Fotolia.  Used with permission. Photo 1.o: In the 1950s James (Jim) F. Holland and colleagues were considered the “cowboys” of chemotherpy. Courtesy: © 2010 – 2018 National Library of Medicine | National Institute of Health.  Used with permission.

Copyright © 2013 – 2018 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


A Call to Action: Submit Your Expertise

Valuable lessons learned from both approved antibody-drug conjugates  (brentuximab vedotin /Adcetris®; Seattle Genetics approved in 2011 and ado-trastuzumab emtansine or T-DM-1/Kadcyla® approved in 2013) as well as novel investigational compounds in ongoing clinical trials, have helped scientists, researchers and clinicians to better understand the mechanisms of action of antibody-drug conjugates.  These lessons have also helped them to find new ways in overcoming the challenges of poor internalization, tumor non-specificity, off-target toxicity, lack of efficacy, low expression levels and multi-drug resistance.

Much work is being done in developing innovate next generation antibody-drug conjugates by improving target selection, finding new cytotoxic drugs as payload, engineering antibodies or discovering alternative effector moieties to increase half-lives, improve target specificity and improve and optimize linker-payload chemistry.

As an online-only, hybrid open-access, peer reviewed journal designed to serve the needs of a diverse community of individuals including academia, life sciences, pharma, (basic, translational and clinical) research, clinicians/physicians, along with regulatory affairs, government authorities and representatives from payers, and policy makers, we strive to offer a the latest information related to antibody-drug conjugates by publishing news and news features, editorials/Op-Eds, as well as peer reviewed research, commentaries, discussions and blogs on topics relevant to a broad and international readership.  Some of this information focuses on (early) preclinical drug development and clinical development. But we also cover articles discussing upstream and downstream processing, characterization and analytics, regulatory affairs, insurance, reimbursement policies, etc.

Planning ahead for 2017
With the fall medical and scientific meetings in full swing and 2017 only two months away, we’re looking ahead to 2017. Each year, as part of our editorial process, we’re looking at the ‘big topics’ for the next 12 months.  Some of our planning is dictated by the medical and scientific meetings* and as a media partner of some of the most influential conferences and symposia in the industry, we will cover the news and late breaking updates presented during these meetings.  Some is dictated by industry and clinical breakthroughs. And some of our coverage is dictated by business transactions and decisions made by regulatory bodies.

But there is more. Our editorial calendar also depends on you! Our planning starts with the development of a comprehensive editorial calendar. Being a continuously published (online) journal, we then look for the specific, relevant, topics guiding our coverage. As part of this process, we’re inviting subject-matter experts and Key Opinion Leaders/KOLs to contribute. And this is where you come in.

Being a subject-matter expert or KOL, we welcome your manuscripts for peer-review. Generally, articles can be a data-driven novel research,  a clinical/therapeutic review, a science-based opinion/Op-Ed, an academic or scientific review, a technical discussion, application note or case study, a policy/legal or regulatory overview/discussion, etc.  Each manuscript, submitted for peer-review to our independent editorial review board, needs to be original, properly referenced and offer timely information focusing on antibody-drug conjugates, targeted therapies and precision/personal medicine suitable for our (experienced) readers.**

In addition to manuscripts for peer review, we invite you – as a contributor – to develop and submit news articles and news features and recommend subjects for the ADC University and video projects.

An Exciting Time
With a new wave of dealmaking, scientific developments and medical breakthroughs, this is an exciting time for anyone involved with antibody-drug conjugate.

Industry-wide there are 60 antibody-drug conjugates in clinical development. Today 40 of these investigational compounds are in phase I trials, 16 in phase II and 4 phase III. Currently, there are two licensed ADCs on the market. Many of the ADCs in phase I trials are not identifying a target disease, but are broadly recruiting for solid tumors. With more than 10 ADCs, breast and lung cancer are common diseases for ADCs. Of the 30 different targets for solid tumors 11 target breast cancer and 9 lung cancer.

With more ADCs moving into later-stage clinical trials in 2017 and other trials coming to a close, we’re eagerly anticipating intermin data as well as mature data from pivotal trials with ADCs in both solid tumors and hematological cancers.  But we’re also looking for the latest (early) pre-clinical data. Data you develop as part of your early pre-clinical studies, your characterization or analysis of novel ADCs, your work in the clinical, etc.

Questions to Ask – Answers that Matter
So, what are the lessons we have learned. And, how are the lessons from currently approved and marketed antibody-drug conjugates as well as novel investigational compounds in ongoing clinical trials helping scientists, researchers and clinicians to overcome setbacks previously experienced? How do initiatives like the Cancer Moonshot impact research? How do the regulators look at novel ADC-construcs with new payloads and linkers, and outcomes from combination therapies? What about characterization, analytics, environmental risk assessments, upstream and downstream (manufacturing) issues, single-use technologies, containment, reimbursement and insurance? And… how do research outcomes translate to success in the clinic and benefit patients with unmet medical needs?

With a scientific and technological revolutions driving the many advances and radical new opportunities in the treatment of patients with cancer and hematological diseases, novel treatment options, including solutions for currently unmet medically needs, are opening up new possibilities for meeting the challenge.

And that’s why you are important.

We’re eagerly anticipating your contributions!

* For an overview of meetings covered by our editors, please visit our Event and Meeting page.
** See our editorial (submission) guidelines.

Last Editorial Review: October 27, 2016

Featured Image: Stack of color magazines on white background. Courtesy: © Fotolia. Used with permission.

Copyright © 2016 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


Death of the Great Laboratory of Clinical Medical Science

Free-market capitalism has brought unimaginable innovations to mankind in the last 200 years, more so than any other economic system in the history of the world: airplanes, telephones, personal computers, electric lightbulbs. Far less appreciated, even by those who are ardent advocates of free markets, are the innovations brought by private medical practices through the magic of free-market capitalism.

Philippa Thomson, who lives in Scotland, describes her battle with an inner ear condition known as Superior Semicircular Canal Dehiscence (SSCD) in a new book titled A Hole in my Life—Battling Chronic Dizziness. The picture of her struggle to get help within the socialized medical system of the British National Health Service (NHS) is not a pretty one. She is eventually tossed aside by a system that shows her little compassion. However, she doesn’t give up and she finds an experienced specialist in the United States who can help her — me.

Medical innovations
People may ask, “How is it that no one in the UK-NHS was able to help her, but a guy in private practice in Louisiana could?” Such people have been conditioned to believe that government or universities are the sole source of innovation. This is far removed from reality.

Throughout the last 70 years, the U.S. has been the greatest mover and shaker in the world of medicine. Most major medical innovations have either been born or significantly developed here. And, many of the major innovations have come from small private practices—certainly not from the government. Innovative changes do not come from out of our universities — they come from individuals who work at our universities. However, true radical, transformative innovations have often come from private practices.

William F. House ( January, 1968).House's first design for a cochlear implant was surgically implanted in 1961, but the implant was rejected by the patient's body. A longer lasting model was developed and successfully implanted in 1969, and it was introduced commercially in 1972
Photo 1.0. William F. House (January, 1968) invented the cochlear implant. His first design was surgically implanted in 1961, but was rejected by the patient’s body as a result of lack of biocompatibility of the insulating material. A longer lasting model was developed and successfully implanted in 1969. The cochlear implant was commercially introduced  in 1972 by 3M Corporation. The House-3M single-channel implant was the first FDA-approved impact and between 1972 and the mid-1980’s more than 1,000 were implanted..

Looking at my field of neuro-otology (inner ear disorders), three major innovations came from private practices. William F. House, DDS, MD, was a medical researcher who invented the cochlear implant, an electronic device considered to be the first to restore hearing to the deaf. He was in private practice and braved skepticism when he was condemned by academics, who claimed it was an assault to shove a “wire” into someone’s ear.[1][2]

John Epley, MD, a solo private practitioner, developed canalith repositioning, or the “Epley maneuver,” which was the single biggest advance in the treatment of vertigo* — ever. He almost lost his medical license due to objections from the academics at the university. Now the Epley maneuver is routine everywhere.

John Joseph Shea Jr. MD, also in private practice, developed stapedectomy surgery, which restores hearing to those who have otosclerosis, a disease that causes the last hearing bone to harden in place. This procedure was initially condemned by academia until eventually accepted and embraced. [3]

You may have noticed a pattern here. Academic institutions are reticent to embrace radical transformative ideas. However, they are great places to refine those ideas, once accepted.

Publish or perish
Academic physicians are paid to do research and write papers. While “publish or perish” is the rule, what gets published is often rubbish. The editors in chief of two of the most prestigious medical journals (the New England Journal of Medicine and Lancet) recently expressed their distrust of the published medical literature, estimating that half of what is published may simply be untrue. What is published has to be accepted by “peer review.” Unfortunately, “peers” usually frown on radical new ideas. Consequently, this restricts the academic to a narrow range of possibilities, or marginal advances rather than great advances. More often, the published papers simply entrench the established viewpoint, rather than challenging it.

Better patient outcomes
In private practice, innovations can only succeed if they result in better patient outcomes and satisfied patients. If not, they are not repeated. There is no pressure to publish. The only incentive is better patient outcomes. The private practitioner’s focus is not constrained by what the peer reviewers will say—only what his patients will say.

Best Practices
Government intervention such as by the NHS in the UK and now Medicare and Affordable Care Act (ACA) also known as ObamaCare in the U.S. constrain physicians’ actions by “best practices” and “cookbook medical decision trees“. These constrained medical decisions have been institutionalized via the electronic medical record (EMR), which has been mandated by the federal government. This not only squelches innovation, but has a chilling effect on physicians’ actions, preventing them from doing anything beyond the regimented government-sanctioned prescriptions.

Imagine if the government had clamped down on doctors and ordered “best practices” in the 1950s? We’d still be stuck with 1950s medicine, without the cochlear implant, stapedectomy, or the Epley maneuver.

Unfortunately, ObamaCare is killing private practice with bureaucracy and nightmarish mandates. In the few years since Obamacare has been enacted, roughly half of doctors in private practice have left for hospital employment. ObamaCare is killing the great laboratory of clinical medical science.

*Canalith repositioning is designed to help relieve Benign Paroxysmal Positional Vertigo or BPPV, a condition in which the patient may experience brief, but intense, episodes of dizziness that occur when they move their head.

Last Editorial Review: July 10, 2016

Featured Image: Young female physician with stethoscope prescribing treatment Courtesy © 2016 Fotolia. Used with permission.

Copyright © 2016 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


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