Dr. Eric Vallières: Engaged on all fronts against mesothelioma

Whether he’s expanding the minds of youngsters at Islander Middle School on Mercer Island, instructing eager surgical residents over the open chest of a cancer patient, leading a debate with thoracic surgeons over multi-modal treatment methods for mesothelioma, or chatting affably while reining in the 300-horsepower rumble of a ski boat, Dr. Eric Vallières is always fully engaged.

Through professional publications and by working on a number of mesothelioma cases, Dr. Vallières had the opportunity to disseminate detailed information about his multi-faceted approach to the disease. As a surgeon, as a researcher,  as a scientist, and as a teacher, Dr. Vallières engages on a whole host of fronts in his quest to help patients stricken with malignant mesothelioma.

Trained from his early twenties, he has become a master teacher. Yet “teacher” misses the mark, for this brilliant and dedicated doctor has none of the quirks and qualities that consign so many “teachers” to the realms of the rigid, boring or flat-out weird. To the contrary: Dr. Vallières’s lessons are so insightful and done with such a deft hand that the listener—or more often, the participant—realizes that he’s been taught after the fact.

Such a light, skillful, and incisive touch is hardly surprising. Dr. Vallières makes his living by giving more life to others as a thoracic surgeon. More than any other medical specialty, this one depends on extraordinary manual dexterity and the ability to orchestrate an entire surgical team. Gentle yet firm, kind and caring, unusually skilled yet as personable as the guy next door, Dr. Vallières is always engaged.

The enemy that never sleeps

Part of his engagement stems from training, part from experience, and much from necessity: Dr. Vallières’s nemesis is cancer, an enemy that always seems to be on the run, and multiplying. Resting and idling are simply not options. Recognized by the University of Washington’s School of Medicine as the Department of Surgery’s “Teacher of the Year” in 1998, Dr. Vallières’s core approach as a pedagogue mirrors his approach as a surgeon. “Well-prepared,” “doesn’t shoot from the hip,” “never absent,” and “excellent teaching skills” were phrases used by those whom he taught.

Small wonder that Dr. Vallières is described in these terms by his students. His principal foe is lung cancer, an enemy which over the years has begun to show its Achilles heel. As surgical techniques, radiation therapy, and chemotherapy have improved, the typical lung cancer patient’s survival curve has moved upward and to the right – indicating better outcomes.

But mesothelioma continues to elude even the most sophisticated human and medical weaponry. Dr. Vallières has spent the last fifteen years engaged in a high-stakes battle with this relentless asbestos cancer that most often attacks the pleural lining of the lungs. It’s not hard to grasp the destructive impact this disease has on patients – the rapid growth of the tumor, its tenacious trespasses, the way it engulfs the lung and slowly suffocates its prey.  These horrors we know about all too well. Tangible, living horrors so large and foreboding the reader is prompted to ask – why would any surgeon invest his time, energy and compassion in what appears to be a futile battle?

Dr. Vallières dug deep to answer that question. “As a physician you want to cure, to heal. As a surgeon, you want to grapple directly with the pathology and cut it out or somehow operate on the affected organs so that they can return to their normal, healthy function. Mesothelioma thwarts the physician on so many fronts—it resists a cure, it grudgingly responds to treatment, and it always seems to recur, often in a remote site that is inoperable.”

Rapidly spreading. Bulky tumor. Refractory to treatment.  Recurrence. This is the dark language of an ugly disease. How ugly?  In the case of mesothelioma patient Robert Treggett, Dr. Vallières summarized the survival numbers.

Roger Worthington: Could you tell the jury a little bit about the survival statistics for patients diagnosed with this disease?

Dr. Eric Vallières: Sure.  If you look in the books, the median survival of patients who are diagnosed with mesothelioma is sixteen months. Now, you know, some patients will be diagnosed earlier, and by such, will appear to have a longer survival, and other patients are diagnosed later and will have a lesser survival, but sixteen months is what you will see out there in the books in general.

The odds don’t look good. What then, must we do?

Devising a new line of attack on a recalcitrant offender

The arsenal against mesothelioma needed new weaponry when Dr. Vallières came to the University of Washington in 1996. He embarked on a new type of tri-modal therapy that combines chemotherapy, surgery, and radiation to shrink, remove, and stave off regrowth of the tumor.

“It’s something I thought of with my oncologist and my radiation oncologist at the University of Washington when I moved there in ‘96. I had already tried it in Canada. The idea of giving patients chemotherapy first, then taking them to surgery, and then treating them with radiation was a way of combining these three standard treatment methods and trying to get the best out of each.”

Dr. Vallières has used this tri-modal therapy for the last eight years in Seattle, and he continues to employ it as the Surgical Director of the Lung Cancer Program at the Swedish Cancer Institute. His expertise with mesothelioma has made him the leading surgeon for this illness in the Pacific Northwest. Most of his patients are referred to him by local pulmonary doctors and pathologists.

“Elsewhere,” he notes, “surgeons will also use a tri-modal therapy, but they start with surgery first and follow with chemo and radiation. Our theory is that by battering the tumor first with chemotherapy and achieving a decrease so that the tumor is in retreat when you operate, you have a better chance of getting out the most tumor possible while also preventing a systemic recurrence far from the original tumor site.”

Pioneering work on the sharpest spear in the mesothelioma arsenal

Vallières was fortunate at the University of Washington to be working with Drs. Bob Livingston and Keren Hunt, medical oncologists who had co-authored in 1996 an important article in the prestigious Chest medical journal. This landmark study showed that in one small cohort of 17 inoperable mesothelioma patients, the combination of methotrexate, vinblastine, and cisplatin yielded an overall response rate of 53% and a projected 2-year survival of 35%. This was, according to Dr. Vallières, “significantly better than previously reports with such advanced disease.”

This work with methotrexate, a member of the folate antimetabolite group of anti-cancer drugs, occurred at the time that chemist Edward Taylor of Princeton University was already doing research with pemetrexed (known to you probably as “Alimta”). The impressive results from methotrexate spurred further interest in pemetrexed and funding from pharma giant Eli Lilly, who, together with Dr. Taylor, rolled out Alimta in 2004 as the first FDA-approved treatment for malignant mesothelioma. The Alimta cohort involved 448 patients, substantially more than the small study with methotrexate, and the effectiveness of Alimta, cisplatin, and vitamin supplements increased median survival time to 13.31 months, tumor regression occurred in 46% of the cases, and extended the time until the disease began progressing again to 6.1 months.

By drawing early clinical attention to the effectiveness of folate antimetabolites such as methotrexate, the University of Washington group played a key role in stimulating interest and research in the chemotherapy cocktail that is now the only standard, approved treatment by the FDA for mesothelioma.

The devil is in the details

“Unfortunately,” says Dr. Vallières, “you can’t peel off the pleura from the diaphragm, so you have to remove the diaphragm with the lung in order to remove the tumor. Nor can you peel off the cancerous pleura from the pericardium, which is the envelope around the heart. So in an effort to remove all the cancer, you also have to remove part of the pericardium.”

In a deposition for Richard Walmach’s mesothelioma case in early 2007, Dr. Vallières explained to the jury which patients are eligible for the extra-pleural pneumonectomy:

Roger Worthington: So not every patient you see with malignant mesothelioma is eligible for the type of surgery that you do?

Dr. Eric Vallières: Most candidates are not.

Roger Worthington: What makes a patient ineligible for the extra-pleural pneumonectomy?

Dr. Eric Vallières: Well, there are three categories. One is their ability to withstand treatment, so it’s a big operation, and they have to have adequate cardiac and pulmonary reserves to withstand the surgery, number one; number two, the type of mesothelioma they have. I’m very selective. If they have non-epithelial malignancy, I will not offer this surgery, and thirdly there has  to be no evidence that the disease has spread outside of the lining itself…the majority of folks are non-candidates because they’re older; they are not fit; they have lung disabilities, cardiac issues, and they cannot handle this treatment.

If it were simply a matter of doing a perfect job on an extraordinarily delicate and complex surgery skirting the heart, lungs, diaphragm, esophagus, and major veins of the heart, Dr. Vallières would by now have racked up a perfect record against mesothelioma. He’s that good and that experienced as a surgical oncologist.

But after the surgery, which removes the affected lung, an array of recovery details come into play that often bedevil the patient’s well-being. “The commonest complication is fatigue,” he says. “Think about it. The patient has now been treated for six or seven months continuously, no respite. Imagine running a full marathon every day for seven months. Now imagine doing it when your physical condition is at its weakest, often when you can’t even eat. Now imagine that that would be easy compared to what a mesothelioma patient goes through.”

Dr. Vallières continues: “Patients get significant, prolonged doses of chemo, then they get radical surgery, and just as they are recovering, bang, here comes the radiation that can be so intense that it actually burns the esophagus so that it’s too painful to swallow. Fatigue and depression can be just as tough an enemy as the cancer itself.”

Getting mesothelioma in his sights

This cycle, repeated over so many patients, led Dr. Vallières to engage in a clinical trial through which the efficacy of his tri-modal approach could be tested. He and a colleague, Dr. Douglas Wood, formed an interdisciplinary team and began accepting mesothelioma patients at the University of Washington in Seattle. Dr. Wood acknowledges that treatment regimens to date have been largely ineffective in substantially prolonging the life of mesothelioma patients. The University of Washington approach is designed to take the best treatments from other regimens and combine them. It may take another decade to determine the efficacy of this approach, but according to Dr. Vallières, it is well worth the effort.

“Mesothelioma has lagged so far behind other cancers in terms of research. If you look at ovarian cancer, which has a similar incidence in terms of diagnosed cases, the progress in mesothelioma treatment has been abysmal. We have to begin rigorously testing the various treatment modalities to find out what works. As a treater, you want to believe that you’re doing the best thing for the patient. Ideally you need randomized phase III trials to evaluate the efficacy of new treatments such as these. Whether such trials will ever be completed for mesothelioma is questionable since the number of patients who are candidates for aggressive treatment is small and it would take too many years for a trial to accrue enough patients to reach statistical significance. For this reason, we have to rely on prospective evaluations of new approaches and compare to historical results.”

With a median survival of 4-18 months and a treatment environment in which there continues to be no accepted, effective curative treatment, the enthusiasm that prompted new approaches in the 1970’s and 1980’s has devolved into a nihilistic philosophy towards finding a cure. Mesothelioma patients are often told to “get their affairs in order” or “take a cruise to Tahiti.” Encouragement and hope have been in short supply as an overall palliative attitude to mesothelioma patients is the clinical rule. The use of the various treatment modalities have all been reported alone or in various combinations but each has been a small, non-randomized trial, with no effect on long-term survival when compared to historical controls of palliative care only.

“The purpose of our trial is to evaluate a combination regimen in an induction mode, followed by a complete resection by extra-pleural pneumonectomy, and then radiation,” says Dr. Vallières.

A combination approach

Understanding the need for a tri-modal approach begins with the fact that surgery alone rarely prolongs survival. Dr. Vallières explained this to the Walmach jury.

Roger Worthington: Have there been proven in the medical literature any long-term survival benefits for patients who undergo extra-pleural pneumonectomy?

Dr. Eric Vallières: Surgery alone, there’s no great data to support it, but as part of a combined approach where you add chemotherapy and radiation therapy, there is some series that suggest that for the right patient there is a group of patients that benefit from this. These are patients who are young, fit, and healthy, have epithelial mesothelioma, in whom you find no nodal involvement at the time of resection.

He continued: “Single treatment modes to early stage mesothelioma have never been shown to improve survival. Originally, aggressive radical surgery saw 30% of patients never leave the hospital alive.. Improved patient selection, better surgical techniques, and better peri-operative care have reduced those rates to 0-9%, but surgery alone doesn’t seem to work,” he says. “In my opinion, for most surgical candidates, the extra-pleural pneumonectomy, which removes the entire lung and pleural surfaces, remains the most effective way to get a handle on the tumor. Unfortunately, the tumor commonly recurs. The combination of surgery and radiation therapy is attractive: it enhances local control over the tumor.”

Explaining the rationale behind the multi-modal therapy, Dr. Vallières explains: “You have to keep in mind that systemic failures are common after the surgery. One trial reported that 11 patients out of 17 who survived the surgery wound up with tumors that recurred distant from the original local tumor. It seemed to us that the addition of an effective, systemic chemo regimen was therefore necessary, even in the early stages. We know that our experience with this chemo regimen is small, but to our knowledge no other chemotherapeutic regimen has shown such promising early results. The bottom line is that we’re hoping to improve outcome and survival.”

The human touch

Staying engaged means more than grappling with the intricacies of surgery and the complexities of designing a reliable research protocol. More than anything, it means staying engaged with the patients and the families that have to live with mesothelioma. The personal engagement and concern that made Dr. Vallières a natural choice among students for teaching awards in 1987, 1988, 1989, 1991, 1992, 1996, and 1999 are the same characteristics that make him beloved by those he treats.

“When Dr. Vallières first saw Bob on the ventilator, he became very, very concerned! He took it so personal!” says the wife of patient Bob Dyer.

Patient Robert Treggett praised the surgical skills of Dr. Vallières, noting that “his precision left only a few areas so minuscule that the radiology treatment plan had to be redesigned to target the exceedingly small areas.” Mr. Treggett just finishing a trip to Africa – five  years after his EPP .

With one hand on the gearshift and the other on the pulse of his patients, Dr. Vallières works compassionately and tirelessly, as a healer, mentor, and friend on the frontiers of treatment for this terrible disease.
To contact Dr. Vallières:

Eric Vallières MD FRCSC
Thoracic Oncology
Swedish Cancer Institute
1221 Madison Street suite 400
Seattle, WA 98104
Phone: 206.215.6800
Fax:     206.215.6801
email: eric.vallieres@swedish.org

Surgeon, Teacher, Advocate, Regular Guy

Dana Point, CA. Dr. Eric Vallières and Dr. Christine Lee join Roger Worthington at a mesothelioma research fundraiser on February 10, 2007, featuring Jordan Zevon and Chris Botti.  A contributor to the Punch Worthington Lab, Dr. Vallières has also been a member of the Science Advisory Board of MARF since its inception in 1999.


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