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Adriana's trial   Adriana Jenkins gets her weekly infusion of Herceptin at the Dana Farber Cancer Institute. (Globe Staff Photo / Suzanne Kreiter)

ADRIANA'S TRIAL

A young life interrupted, an experiment begins

Despite the risks, thousands seek to enroll
in clinical trials of experimental drugs

By Raja Mishra, Globe Staff, 4/28/2002

First of three parts

   
 THE SERIES

Part 1
An experiment begins

Part 2
A cancer patient's longest wait

Part 3
Balancing benefits and risks

Follow-up
Cancer drug's link to heart ill probed
Trials continue in different form

 PHOTO GALLERY

Photos from Adriana's experience

By Suzanne Kreiter / Globe Staff

 TIMELINE

Herceptin's history

 CLINICAL TRIAL

To gain FDA approval for widespread use, a new treatment must successively pass three phases of clinical trials, each seeking to answer different questions:

Phase I: Is a new treatment safe? What are safe dosage levels? Usually small trials, often with less than a dozen patients.
Phase II: How well does the treatment work? What are its side effects? (Adriana Jenkins is in a Phase II trial.)
Phase III: Does the treatment heal more effectively than standard treatments? Does it work consistently in a large group of patients? This phase often involves hundreds of patients in many hospitals.

 HERCEPTIN

About 30 percent of breast cancers produce excessive HER-2 proteins, which makes cancer cells proliferate. Herceptin disables HER-2. It hits only HER-2 producing cancer cells, not normal cells, minimizing side effects and earning it the title "smart" drug. UCLA's Dennis Slamon spent 13 years developing Herceptin. San Franciso-based Genentech Inc. sells it. The first large-scale clinical trial results came out in May 1998: 78 percent of patients on Herceptin plus chemotherapy survived one year; compared to 67 percent on chemo alone. The FDA approved Herceptin for treating metastatic breast cancer, where the cancer has spread. Doctors now seek to extend its use to earlier stages of cancer through clinical trials, such as the one involving Adriana Jenkins.

 RESOURCES

Dana Farber research advances
ClinicalTrials.gov
CenterWatch
CRnet from MGH and Harvard
Clinical trials search
NEMC: The Cancer Center

 ABOUT THIS SERIES

The Globe followed breast cancer patient Adriana Jenkins through a clinical trial at the Dana Farber Cancer Institute in Boston for eight months. A reporter and photographer were given access to most medical events and records. All conversations reported were witnessed. The lengthier exchanges that appear in the stories were recorded on audio tape. Jenkins' writings, as well as representations of her thoughts, were taken from contemporaneous notes written by her and supplied to the Globe on a regular basis throughout the eight months.


Adriana Jenkins doubts God exists. Or fate. When we die, she says, we are gone - ''ashes to ashes, dust to dust.'' But she imagines it often: pain, then floating upward, looking down on mourners around her hospital bed, a shimmering light and finally nothing. ''Off like a light switch,'' she says.

Adriana sits on a bed at Dana-Farber, in heels, black slacks, and an apple red blouse. She has tied back her long, luxurious hair. The window holds a sweeping view of the Boston skyline, a crystalline day on which there are distractions: a wedding dress to fit, blurry memories of last weekend's bachelorette party, a chiming cellphone, her 32nd birthday to plan.

She has breast cancer. It is aggressive. Even with the full range of standard treatments, doctors give her only a 40 percent chance of remaining cancer-free over the next five years. If cancer returns, her survival odds would be dismal. Forty percent, five years. It rang in her mind when she was told; it echoed through her dreams. And just when life was coming together.

Adriana had found love - David Halligan, her fiance, her best friend. They dreamed of buying a cottage in a quiet Midwestern town. They planned on simple dinners together. Now she was told, 40 percent, five years. She was only 31. She could not settle for this. No way. She needed something better.

So Adriana Jenkins consented to be a test subject. Today, Aug. 30, 2001, a nurse brings a plastic packet filled with a clear liquid, called Herceptin, developed by dozens of scientists over two decades at a cost of hundreds of millions of dollars.

This is a clinical trial, the heart of Boston medicine, the gateway to medical progress. At any given time last year, more than 3,000 trials were taking place in Boston-area hospitals and clinics. The Globe followed Adriana for eight months for a detailed look into this world - a world dominated by uncertainty yet infused with hope.

''The day we found out,'' Adriana wrote in her journal, ''we met back in the apartment, just collapsed on the couch and cried in each others' arms. I kept saying, `I'm sorry,' because I am so sorry that he has to go through this, too - this isn't exactly what he signed up for in life, either. ... Our future changed from being a large, open door to a series of smaller windows.''

Sixteen weeks after that awful day, the nurse hooks an IV line to her chest. She has been among the first test subjects in Dana-Farber IRB Protocol No. 00-273, a clinical trial under the direction of Dr. Eric Winer. Adriana stares blankly at the bag containing the Herceptin. She swallows. Hope for a future lies within the bag.

Clinical trials are rarely black and white, success or failure. They begin with uncertainty. They can end with uncertainty. And while trials promise healing, they can deliver harm. For a trial subject, hope, sorrow, and confusion intertwine. All this, Adriana will come to understand.

Today is her seventh of 12 scheduled Herceptin doses. A brick-size machine, gently whirring, pumps the drug from the bag, through the IV line, into her body. She looks out the window. Adriana Jenkins does not believe in God or an afterlife, but she thinks, just maybe, her mother watches over her.

Her mother, Georgeanne Jenkins, was diagnosed with terminal lung cancer a decade ago and given a year to live. Adriana planned a year off from college to spend time with her. But Georgeanne died in six weeks. And Adriana realized that life can end without notice or fanfare in a sterile hospital bed without time to say goodbye.

The drug-dispensing machine chimes softly three times, ending today's treatment. Five more remain. In two months, she will find out if the drug has worked. And if she can reclaim her future.

Life interrupted

Adriana was born in Minneapolis and raised in Largo, Fla. Her father, Adrian, a retired commercial pilot, shuttles between homes in Florida and England. Friends call her a no-nonsense, take-charge person but also extremely thoughtful. She still phones high school chums and has a wide circle of friends drawn from different periods of her life.

While attending Boston University, Adriana planned a career in public relations. She studied journalism, then moved back to Largo, attempted to start a PR firm and worked for a real estate magazine. Finally, miserable, Adriana decided Boston was the place to be, job or no.

She eventually found public relations work at Children's Hospital, before moving on to other jobs. It would come to be a serendipitous connection.

In spring 2001, Adriana discovered a lump in her right breast. It reddened. It swelled. After two inconclusive checkups, she scheduled a mammogram, after which her life began spiraling downward. A Dana-Farber doctor ordered her immediately to Beth Israel Deaconess Medical Center for an ultrasound test, and before she knew it other doctors were piercing her breast with a needle and pulling out tissue and then the tears came, along with a sense that none of it was real.

On July 10, as she sat at her work desk, a quick phone call came from her doctor: ''It's cancer ... you're so young.'' Click. She looked up at her fellow Regan Communications colleagues. They were typing away.

After running out to the parking lot and breaking down, she returned home to cry with her fiance, Dave, spent hours dwelling on her mother's death, and then started telephoning people she knew from Children's Hospital.

One, Bess Andrews, a former colleague there, called around and learned about Dr. Eric Winer. Winer was a breast cancer research star, the best of the best in a town filled with the best, Andrews heard. Adriana immediately scheduled an appointment. Days later, Dana-Farber doctors were conducting CAT scans, X-rays, and MRIs on her swollen breast.

The bad news: Stage III inflammatory breast cancer, with significant tumors in her breast that had spread to the lymph nodes in her armpit. And it was on the cusp of spreading farther. Thus, there was only a 40 percent chance, even with treatment, that the cancer could be vanquished for five years.

The ''good'' news: HER-2. Her cancer produced large amounts of this protein, as about 30 percent of breast cancer patients do. It was causing her tumor cells to proliferate madly. It drove her cancer. And it could be precisely targeted by this new drug, Herceptin.

Winer happened to be starting a new test of the drug on women with Stage II and III breast cancer. Adriana found herself in the right place at the right time.

Dana-Farber doctors receive calls from around the world, desperate patients begging for access to some trial, any trial. Few get in. Other test patients are sent over by local doctors. Some trials are advertised, and patients simply call. Last year tens of thousands of patients, from around Massachusetts, the United States, and the world, took part in Boston-based clinical trials. Adriana Jenkins became one of them.

Becoming a guinea pig

Winer met with Adriana to explain the trial. He presented her with a 12-page contract, the ''Research Consent Form.'' It is an essential safeguard: Test subjects must, in advance, know precisely what will be done to them and all the risks involved. And they must give their consent, free from pressure, free from inducement.

The contract laid it all out in simple, stark terms. The trial would last 15 months. Forty women would participate. The trial would test the combination of Herceptin and another drug, Navelbine. Winer invented the approach. In an another test, this combination dramatically helped women with breast cancers more aggressive than Adriana's, he explained. There was ample reason to think it would help her.

This was a phase II trial, the contract explained. A phase I trial had proved the regimen safe. This phase would determine its effectiveness.

But it was far from certain Herceptin-plus-Navelbine would work. This was a test, after all. So she would get a backup: a mastectomy, chemotherapy, and radiation. Standard treatment. Even if the experimental therapy did work, she would have to endure all this.

The possible side effects took up four pages in the contract. Navelbine and two other drugs involved - Taxol and Adriamycin - had been widely used. Their side effects could be anticipated. But Herceptin was not so well understood. There were signs, from studies, that it was toxic to the heart, at least in some women.

''As is true for any drug, unknown and potentially life-threatening side effects could occur with Herceptin and Navelbine,'' the form read.

On the other hand, Adriana's participation would advance cancer research. The form noted the trial could eventually help other women. That, however, did not make much of an impression on Adriana. She simply wanted to live.

''I had no problems being a guinea pig!!'' she wrote in her journal.

Adriana signed the contract for Protocol No. 00-273 with a flowing cursive `A,' dated ''7/19/01.''

The trial unfolds

It is Sept. 5 and Adriana sits for her eighth Herceptin treatment. She has been slightly nauseated and a little tired. But that's it. Herceptin, many doctors say, is the mildest cancer drug in history. In two months of treatment, Adriana has worked a full schedule for the marketing department of Millennium Pharmaceuticals in Cambridge, where she told her new boss about her breast cancer and he smiled and said no problem.

Every week, Dana-Farber doctors examine her, check her vital signs, and chart her progress. Then for an hour she is fed Herceptin and Navelbine intravenously while sitting in a lounge chair beside dozens of other Dana-Farber patients, some bald, some emaciated, all hoping the drugs flowing into them will help. A nurse records her dosage, which varies slightly every week depending on her weight. She knows little about the other women in the trial.

Before today's Herceptin infusion, Winer examines her breast, kneading, pinching. The swelling and redness disappeared weeks ago.

''Sure looks the same,'' he says. ''You've had a great response. It qualifies as a complete clinical response. Keep it up and we'll see you next week.''

''I feel great,'' says Adriana.

''You're doing great, but I want you to be prepared for there being some cancer there,'' he replies.

In six weeks, surgeons will remove her breast. They will examine it for tumors and cancerous cells. Only then will they know how well the drug worked. Adriana's hopes are pinned on the day. She imagines Winer bounding into a room, proclaiming that it is safe, once again, to dreamily imagine a long, quiet life with Dave by her side.

''But this is as good as it can be at this moment,'' says Winer.

Oasis of bliss

She fell for David Halligan in 1998. Until then, love often meant long nights at Back Bay watering holes, where awkward men tried to woo her with their resumes. She was approaching 30. Why could she not connect with anyone? Dave roomed with Adriana's cousin in Winnipeg. She came for a visit that August. They had crossed paths a year earlier. But this time was different.

''It was immediate,'' he recalls.

She walked into the apartment wearing a black sweater and khakis. Her straight black hair flowed to her shoulders; her eyes glowed. She was blunt. She commanded attention. Yet, when talking to you, her head tilts to the side, her eyes meet yours, you feel like the only person in the room, Dave says. He was smitten.

But he was also involved with someone else. Dave sent her an e-mail, anyway. E-mails led to visits, which led to passion, and in July of 2000, Dave quit his accounting job in Winnipeg, packed his car, and moved to Boston with no plans save to marry ''the love of my life.''

Suddenly two people were anchored in one another, living together in Brookline.

Dave speaks softly. He is cheery, a Canadian, an optimist by nature, he says. But then came cancer. They had just gotten engaged. The long-term dreams, the quiet cottage, disappeared in a flash. But Dave remains an optimist.

Call off the marriage? Never. The 40 percent, five years prognosis? Don't believe it. A wife without a breast, hair or energy? I love her. Bad luck? ''No, life is what it is,'' he says.

And so on a luminous Martha's Vineyard day in mid-September of 2001, Adriana is wearing a strapless white dress and standing before an altar.

Two days earlier her shoulder, where IVs had been hooked, began to swell. Fly back to Boston if you get a fever, her doctors said. She cried. And two days before that was Sept. 11. Half the guests couldn't fly over, and the Italian honeymoon was cancelled.

But here she was, feeling fine, beaming in front of 60 guests, including dad. Some drove four days from Winnipeg. Those who made it found a wrapped assemblage of wine, bottled water, candy, pretzels, and nuts in their hotel rooms, Adriana's handiwork.

The grass is bright green, the sky clear blue, the temperature mild, the slight breeze warm. The last months have been hard. Some mornings, Adriana would awaken in tears. But hope arrived in a new drug. In just a few weeks, surgeons will cut off Adriana's breast, so they can determine whether it is clear of cancer and whether this marriage could be a long one. But today, for a moment, that is all part of another world. This day on the Vineyard is an oasis. There is only Dave and he is smiling and holding her hands.

The ceremony is short. Dave slips a ring on Adriana's finger. It is her mother's platinum wedding band.

At the reception, the band is a bit flat and the small gathering refuses to dance. But there is much drinking. During the old blues number ''Come Rain or Come Shine,'' Dave takes the mike, picks up a guitar, and does his best Eric Clapton, and the guests clap in delight. Adriana, staring, laughing, swells with love and knows it is right.

The surgery

It is a busy mid-October day in the Brigham and Women's Hospital surgery unit. Adriana lies in a pink-and-blue hospital gown. A nurse jots down insurance information, then takes her temperature.

This is the last time she will have two breasts. Dave looks on, silent. Adrian Jenkins, her father, paces. The anesthesiologist whispers in her ear and her smile turns to a frown and she starts crying.

''I can't watch this,'' says her father.

Dave's hand is on Adriana's. They hug. He walks out of the surgical prep area. The anesthesiologist reminds him: ''Dave, don't look at the clock. It takes as long as it takes.''

Dr. Dirk Iglehart, an old Duke Medical School chum of Winer's, will perform the surgery.

They must cut off as much of the right breast and remove as many nearby lymph nodes as possible, to ensure no diseased tissue remains. But more important is what comes after. Did the Herceptin kill the cancer? Everywhere? Or did it resist and multiply and possibly spread? Adriana is slowly wheeled toward the operating room.

The answers lie within her breast.

PART 2:  The surgery, the results, and a mysterious development

This story ran on page A1 of the Boston Globe on 4/28/2002.
© Copyright 2002 Globe Newspaper Company.

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