It was the mid-1960s and Barnett Rosenberg, PhD, was curious about cell  division. The Michigan State University biophysicist had watched the process  under a microscope and noted the cells looked much like the pattern created by  iron filings as they wiggled and moved when placed near a magnet.

Would changing electrical conditions around the cell change this pattern the  same way it did with the iron filings? To test his question, Dr. Rosenberg and  colleagues Loretta VanCamp and Thomas Krigas, PhD, began experimenting with  electricity and bacteria, stumbling upon the finding that when platinum  electrodes were used to send an electrical charge through bacteria, it was not  the electricity that caused cell division to stop, but some kind of  electrochemical reaction. What they found upon further research was that the  electric current had prompted a chemical reaction between the normally  unreactive platinum in the electrodes and nutrients in the solution containing  the bacteria, and, in this reaction, a compound was produced, a molecule  centered on a platinum atom called cis-diamminedichloroplatinum—or C-DDP.

The compound was not new, having been discovered in 1845. Almost 50  years later, Alfred Werner, PhD, determined the structure of DDP and won a Nobel  Prize in 1913 for this discovery. But Dr. Rosenberg and his team reasoned that  if the compound inhibited cell division, it might be a useful cancer drug. They  pursued the development of the new compound, which they called cisplatin  (Platinol®).

While its exact mechanism for stopping cell division has never been fully  understood, cisplatin appears to cause cell death by damaging the DNA (genetic  material) of the cell. Cisplatin was soon credited with  providing the first cure of an advanced solid tumor when Lawrence Einhorn, MD,  proved its efficacy in testicular cancer. Ultimately, Dr. Rosenberg and his team  created a sister drug called carboplatin (Paraplatin®) that was similar in  molecular makeup but promised less severe side effects than cisplatin.  Carboplatin is widely used in treatment of a number of cancers, including  ovarian, lung and breast cancers.

When the Food and Drug Administration  approved cisplatin in 1978, it had already been in use for more than four years  by Dr. Einhorn and other oncologists for treating testicular cancer. Since then,  cisplatin has been widely used against a number of other cancers, including head  and neck, cervical, esophageal and ovarian cancers.

Frank Pasqualone,  senior vice president of oncology for Bristol-Myers Squibb Company, watched the  evolution of cisplatin as its product manager.

“The early story of  cisplatin is a dramatic story of the collaboration of academia, industry and  government,” he says. “There was no question that it was a good drug, but its  tolerability was a major concern. (The side effects of cisplatin included severe  nausea, kidney damage and nerve damage.)

The second chapter in the  cisplatin story began when Zofran® (ondansetron) was introduced as the first in  a new class of antiemetics. Zofran and the similar drugs that followed  revolutionized cisplatin administration as patients had much less nausea and  vomiting than before.”

The literature is replete with references of  cisplatin and carboplatin use in esophageal, lung and gastric cancers, in  addition to those mentioned above. But none proved to be the cure found for  testicular. Today, Pasqualone says, research is moving away from the “shotgun  strategies.”

“We know now how insidious cancer is and are investing in  the new wave of targeted therapies that are easier on the patient. In addition,  we are constantly learning more and more about predictive markers, which may be  more indicative of who may benefit from a given therapy. Our collective goal as  a cancer community is to find the same kind of cure for other solid tumors that  was found for testicular with cisplatin.”

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Finding a Magic Bullet

The moment: September 1974. John Cleland was dying. He had failed three grueling chemotherapy regimens, his weight had dropped to 106 pounds, and the cancer that began in his right testicle had now spread to his lungs.

The doctor delivering the bad news, Lawrence Einhorn, MD, a medical oncologist at Indiana University Medical School, had been seeing the 23-year-old Cleland since his initial diagnosis a year earlier in November 1973.

They sat in Dr. Einhorn's office. Neither spoke.

"I think he felt sorry for me," says Cleland today. "Finally, he said, 'Well, there is one other thing we can try.'"

Three weeks after his first injection of the then experimental drug Platinol® (cisplatin), Cleland was back at the hospital for his second treatment. From the vantage point in his hospital bed, he recalls sensing rather than actually seeing that something was happening in the hall where Dr. Einhorn and oncology nurse Becky Bond were viewing the new scans of his lungs. When Dr. Einhorn walked into his room he was smiling; Cleland knew something was up.

“He just looked at me and said, ‘John, I think you are going to make it.’”

The scans were clear. They were so remarkably different from Cleland’s previous scans that the radiologist was concerned he had confused Cleland’s films with another patient. He hadn’t. The tumors in Cleland’s lungs were gone, melted away.

The fortuitous meeting of patient, doctor and drug heralded a moment that thousands of cancer patients dream of—cure. But that it almost didn’t happen underlines the often serendipitous discoveries of cancer treatments.

In the early ’70s Dr. Einhorn found himself at a crossroads. Since beginning  medical school his path had been clear—become a cardiologist and go into  practice with his father in Dayton, Ohio. But his father had become ill and  retired, leaving the son open to other possibilities.

“We were allowed  to take an elective during the last two months of internship and I took  hematology oncology to see what it was like.”

What Dr. Einhorn found was  a field that was wide open to discovery and where the patients had significant  symptoms and illness. After the first round he decided to do a second, being  drawn into a specialty he found was “more complicated and more  human.”

“Everyone faces illness, but I was struck by what cancer patients  go through compared to other patients,” says Dr. Einhorn, who was now enamored  by the challenges and faces of cancer.

Dr. Einhorn was also drawn to the  idea of research and teaching. A two-year stint in the military gave him time to  confirm his sense that oncology was a place where he could make a  difference.

Oncology was still a new field in the early ’70s and to get  additional training after one year at IU Medical Center, Dr. Einhorn had four  options: the National Cancer Institute in Washington, D.C.; M. D. Anderson  Cancer Center in Houston; Memorial Sloan-Kettering Cancer Center in New York  City; or Roswell Park Cancer Institute in New York. He chose Texas, returning to  Indiana in 1973 where he began working with John Donohue, MD, a surgeon who was  exploring treatments for testicular cancer.

When he began working with  Dr. Donohue, Dr. Einhorn’s exposure to testicular cancer had been limited to  only a few patients in Texas, but he knew, as Dr. Donohue did, that it was a  killer once it moved beyond the testicle. Indeed, at the time the cure rate was  only 5 to 10 percent. Both physicians knew there had to be a better treatment  for this cancer, which took mostly young men.

One of the first papers Dr.  Einhorn read about treating testicular cancer looked at a very small sampling of  patients with testicular cancer who had been given a new platinum-based drug  called cisplatin.

The drug was only seconds away from being  rejected, Dr. Einhorn says, because of toxicity to the kidneys and other side  effects, such as severe nausea, vomiting and nerve damage.

Dr. Einhorn  felt he might be able to address the kidney issues with hydration and the nausea  with antiemetics. He designed a protocol that would cap the dosage at four  courses over three months to reduce other side effects.

But there was still the issue of finding the right patient. “You can’t just  pick someone and say, ‘I am going to treat them,’” Dr. Einhorn says. “You had to  get the drug protocol, have it approved by the institution and then you can get  a patient. John was the first eligible patient.”

Cleland was also the  right patient because nothing else had worked. He had no other options.

John Cleland married his college sweetheart, Judy, on June 2, 1973. Two months  later, he found a hard spot on his right testicle.

Because it didn’t  hurt, Cleland, who was busy finishing his last semester at Purdue University  with a major in animal science, paid little attention to the spot. When it did  begin to hurt, he saw an internist who reassured him it was nothing, but “just  in case” referred him to a urologist.

Between the internist visit and  the urologist visit, the testicle swelled in size. In early November, Cleland  saw the urologist on a Tuesday and had the testicle removed on Thursday morning.

At 22, Cleland learned he had testicular cancer.

At first, he  says, he wasn’t overly concerned.

“After the orchiectomy they sent me to  the IU Medical Center to have the retroperitoneal node dissection in a  nine-and-a-half-hour operation.”

Cleland, who underwent the node dissection  on his parents’ 26th wedding anniversary, came out of surgery with a scar from  his waist to his breastbone. Of the 53 nodes removed, two indicated microscopic  malignancy. A few days later he met Dr. Einhorn for the first time and began  standard chemotherapy.

Only three months later in February 1974, the  cancer was back. This time Cleland started a chemo cocktail that included  Adriamycin® (doxorubicin), Blenoxane® (bleomycin) and Oncovin® (vincristine),  referred to as ABO.

“Those drugs got your attention,” Cleland recalls.  “We were living in Lafayette and Judy was working full time and going to school  full time to finish her engineering degree from Purdue, so my parents or friends  would bring me down for treatment. With the ABO I went from 158 to 106  pounds.”

Cleland suffered mouth sores so severe he couldn’t eat or drink.  He spent some 60 days in and out of the hospital from February to June, and his  physical condition deteriorated. He recalls one day in early June 1974 when Judy  suggested they sit outside their apartment and enjoy the day.

“So we did.  We went out and sat under a tree and when it came time to go in, I couldn’t get  up. I half crawled and got about halfway to the apartment and my cousin came by  with her husband, Nelson, and their little boy. Nelson picked me up like a baby  and carried me inside. I was in bad shape.”

By July, Cleland couldn’t  handle the ABO combination and Dr. Einhorn switched to Actinomycin D  (dactinomycin) once a month, a drug Cleland says made the others look easy when  it came to nausea and vomiting. In September, Cleland had his fateful  conversation with Dr. Einhorn.

“Until then I was always confident I would  survive,” says Cleland. “My heart was pounding. My mind was racing. I didn’t say  anything and he didn’t say anything.”

Then Dr. Einhorn recommended an  experimental drug called cisplatin. Cleland discussed the drug and his prognosis  with Dr. Einhorn, he says, exploring how long he might live and progression of  the disease.

“I thought, ‘Well, I don’t have anything to lose. I might as  well try it.’”

Cleland doesn’t hesitate as he recalls his first injections,  drawing on the survivor’s crystalline memory of moments in the cancer  journey.

“I had the first injection on October 7, 1974 of cisplatin,  Velban® (vinblastine) and bleomycin. I was in the hospital for five days and got  an injection every day.”

It was when Cleland went back for the second  treatment that everyone watched a miracle unfold; 10 days after the first  treatment, the metastatic tumors were gone from his lungs.

“I was lying  there thinking about getting my things in order,” Cleland recalls, “and then Dr.  Einhorn comes in, and I can tell you this, when he told me the news I was not  touching the mattress, I was floating. It was the greatest feeling in my life.”

Cleland says he called his wife immediately but couldn’t get her on the  phone. The second call was to his parents. Only the week before, he had told his  dad he didn’t think he was going to make it and asked him to tell his mother.

“I don’t remember my exact words but I told her what Dr. Einhorn said  and we cried like babies.”

He underwent two more treatments, one on  Thanksgiving Day, which his nurse came to his home to provide.

Then it  was time to watch and wait, a grueling period of not knowing for the doctor and  the patient. Indeed, the entire oncology community was holding its collective  breath to see if indeed a metastatic solid tumor could be cured.

Six  months later when the cancer had not reappeared, there was hope. A year later  when the cancer had not reappeared, there was a new word being used: cure.

“The initial dramatic resolution of tumor was very gratifying and in all  honesty very surprising,” Dr. Einhorn says. “The larger moment was that these  remissions were durable, and at a year out we had about a dozen patients who  were remaining in complete remission, which, because of how fast the metastases  grow, was remarkable. We knew then that even if there were a few people, it was  doing something incredible.”

It’s a Sunday morning and John Cleland sits in his Indianapolis home and recalls  those days with a clarity that cancer survivors know well, despite the fact that  it has now been 30 years since his treatment.

He jumps up when he hears  the car return from church and welcomes home his wife of now 31 years and  16-year-old twins, Brice and Cecelia. The Cleland’s older son, Chris, is  finishing his junior year at Purdue. This father is quick to point out each  child’s academic and athletic accomplishments.

When the Clelands talk  about the cancer experience, it’s clear its impact remains an indelible part of  their current lives. John Cleland describes the period when treatment was over  as the best of times and the worst of times.

“It was the best because of  the need Judy and I had for each other at that time and the relationships we had  with family and friends. You appreciated each and every day and all the small  things,” he recalls.

During the months of watching and waiting, John and  Judy Cleland tried to get back to being a young married couple planning for the  future, one that now included many unanswered questions. It affected both in  myriad ways.

John Cleland, whose lifelong goal had been to manage a dairy  farm, had completed his degree and taken a job at the University of Missouri  before cancer forced him to return to Indianapolis and treatment. His next job  was regaining his health. When it appeared the remission was going to be  durable, he felt he wanted to give back. He earned his teaching certificate in  biology and began teaching at Zionsville Community High School, a job he  continues today.

Judy Cleland, despite pursuing an engineering degree  from Purdue, always saw her future as a full-time mother.

“John’s cancer  made me more of my own person,” Judy Cleland says. “All of a sudden it was no  longer that I was going to work for a few years, then quit, have four kids and  be a Brownie leader the rest of my life.”

Instead of rural farm life, the  Clelands stayed in Indianapolis. And when Judy was offered a job, John  encouraged her to take it since she had assumed the financial responsibility for  the family during his illness.

“I owed her everything I had. It was an  interesting dynamic,” Cleland says. To which Judy quickly replies, “We just did  it. That is just what you do. I like to say that the women’s movement hit us a  little early.”

By the time the couple began a family, Judy Cleland had  established a successful career as an environmental engineer, consulting with a  number of private companies as well as the state of Indiana, a career she  continues to build while also balancing family demands.

“We waited 10  years to have children,” Cleland says, explaining that despite the severity of  his treatment, they were conceived naturally.

Christopher Blane Cleland  was born June 4, 1983 and named for two friends who had seen the Clelands  through cancer. Twins Brice and Cecelia were born five years later.

Ironically, it was the summer his first son was born that Cleland ended  up back in the hospital with a late effect of chemotherapy—viral myocardiopathy,  a condition he discovered while training for a marathon that requires he keep  his heart rate below 140.

But soon life became one of children and school  and athletics for the Clelands. And, while Judy Cleland says she mostly looks at  the cancer as ancient history, she wanted to honor what she calls John’s  indomitable spirit by nominating him to carry the Olympic torch in the 2002  relay, which traveled through Indiana.

Out of more than 200,000 Hoosiers  nominated, Cleland was one of 142 to carry the torch, running along a stretch of  Indianapolis street lined with family, teaching colleagues, friends from college  and former students.

Dr. Einhorn and the Clelands have remained friends  over the years as it became clear Cleland had indeed been patient zero for what  would become the standard treatment for men with advanced testicular cancer.

Today advanced testicular cancer has a 75 percent five-year survival  rate, and Dr. Einhorn estimates more than 100,000 men and boys have been cured  of testicular cancer since John Cleland agreed to the first treatment of  cisplatin.

The Clelands threw a party in 1999 to celebrate 25 years of  remission and honor the family and friends who supported them. More than 100  people came, including Dr. Einhorn, the nurses who cared for Cleland and friends  and family. Cleland recalls that it was an eye opener for his children,  particularly for his oldest son Chris.

“He said, ‘Dad, I knew you were  sick, but all these people told me how really sick you were,’” Cleland says. “It  just hasn’t been a part of their lives.”

Few of his colleagues at  Zionsville Community High School don’t know about Cleland’s history. In fact, he  is often called upon to talk to young men who are newly diagnosed, and he is the  resident expert in health classes, which in Indiana are required to discuss  early detection for both breast and testicular cancer.

Cleland’s  colleagues were eager to talk about his commitment to teaching, his leadership,  his love of his students and his spirit, which was all summed up by Principal  John Eggers.

“John doesn’t have bad days,” Eggers says.

Today, as Cleland continues to educate about testicular cancer, Dr. Einhorn  continues looking at new uses for cisplatin in other cancers and a way to treat  the 25 percent of men with advanced testicular cancer who do not respond to  cisplatin. Although testicular cancer only accounts for around 1 percent of all  cancers in American men, it remains the No. 1 cancer killer of men between 15  and 34.

“These are often teenagers and we keep looking at what we can  do,” says Dr. Einhorn, who is encouraged by new discoveries such as Velcade®  (bortezomib) and Gleevec® (imatinib) and hopes other new drugs for those who  fail chemotherapy for testicular cancer are just around the corner.

Cleland and Dr. Einhorn talk a few times a year, and Dr. Einhorn had a  special surprise for Cleland at his 25th celebration party in 1999.

During the party Cleland was called to the phone by a friend who said  someone wanted to talk to him.

“I said hello and this guy says he is  Lance Armstrong and I kept saying, ‘Sure, who is it really?’ He convinced me it  was him because he knew some piece of medical information that Larry probably  told him. He thanked me for being the first. I told him I didn’t have a choice.”

While Cleland was one of Dr. Einhorn’s first patients, undeniably his  most famous patient is cyclist Lance Armstrong, who sought out Dr. Einhorn after  his advanced testicular cancer diagnosis in 1996. Armstrong had been given a  less than 40 percent chance of survival at diagnosis because his cancer had  already metastasized to his lungs, brain and abdominal lymph glands.

Dr.  Einhorn watched Armstrong win his first Tour de France in 1999 from his home in  Indianapolis. “Pride doesn’t even express my feelings when I saw him,” he says  today. “He had overcome so much and become such a better person. From a focus on  himself to the focus on the cancer community.”

Cleland had a chance to  meet Armstrong face-to-face when he and Dr. Einhorn were on the stage to greet  the cyclist when he rode into Indianapolis during the 2003 Cycle of Hope. Dr.  Einhorn sent out invitations to former testicular cancer patients to join him at  the city’s field house, thinking he would introduce Armstrong and a few patients  would show up.

“They opened the door at 9 a.m. to the field house where  the event would take place and here came all these men and their wives and  children. I was looking at my life’s work walking toward me.”

More than  300 former patients came that day, and Dr. Einhorn recalls that when he went to  the microphone and said, “Hi, I am Larry Einhorn,” there was a five-minute  standing ovation.

“I introduced Lance after the applause died down and he  got great applause. I whispered in his ear that I thought they liked him. He  said, ‘Yes, but they love you.’”

Winter 2004 | CURE

Finding a Magic Bullet

Cured: The John Cleland Story

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