Dr. Sholler was the only one in the end to tell us yes. We just ran out of time.

Penelope passed away but she is still inspiring millions. Her parents are doing amazing things for children’s cancer. Check out their website at:

www.solvingkidscancer.org

By GEETA ANAND

NEW YORK — John London, a successful hedge-fund executive, is desperate to save his 4-year-old daughter, who suffers from a rare cancer. She clings to life at New York University Medical Center here, sucking her thumb and clutching her favorite teddy bear.

For the past month, Mr. London has been begging a small biotechnology firm to allow Penelope to be treated with an experimental cancer drug that might help. Mr. London has received high-powered support: Several legislators, including House Speaker Nancy Pelosi, have lobbied the company and its board to make the drug available. The Food and Drug Administration isn’t blocking the way.

[Photo]Penelope London

Neotropix Inc. of Malvern, Pa., says it would like to help, but the drug may not be safe for a child and dispensing it would be bad business. “For us to provide the drug to this child would be to put at significant risk a small company with limited financial resources,” says P. Sherrill Neff, managing partner of Quaker BioVentures, a major investor in the firm, which is trying to tie up a vital round of financing of about $20 million. “You could delay the opportunity for lots of patients to get this drug if you sidetrack it for one patient,” he says.

The deadlock reflects an increasing tension between individual patients and companies using the revolution in understanding biology to develop new medicines. Ideas for treating deadly diseases are proliferating, and the Internet carries hints of promising results into the homes of dying patients. They are pushing for the chance to bypass the laborious approval process and receive quick access to experimental drugs when all else has failed.

In the U.S. Court of Appeals in Washington last month, a lawyer for a patient-advocacy group argued that patients’ constitutional rights are violated when they are deprived of medicines in testing that could save their lives. The Abigail Alliance for Better Access to Developmental Drugs wants the FDA to allow patients to buy drugs in testing directly from companies and to allow the companies to profit from the sale. A three-judge appellate panel last year ruled in favor of the alliance. The FDA appealed the case to the full appellate court, which is scheduled to rule later this year.

Lawyers for the FDA argued that broad access to experimental drugs could harm patients and undermine the incentive for them to participate in clinical trials, the studies companies are required to perform in humans to prove safety and efficacy.

“This is a huge dilemma we face as a society — it’s moral and it’s ethical,” says Patty Delaney, director of the FDA’s cancer liaison program. “We have the incredible pain of an individual — sometimes it’s a 4-year-old child, which pulls at everyone’s morality — versus the societal issue of what happens if a small biotech company diverts its resources to a child or ill mother?”

Mr. London, 40 years old, was raised in Manhattan and spent seven years at Highbridge Capital Management, one of the largest hedge funds in the world. He co-founded SuttonBrook Capital in 2002 with $30 million in capital and built it into a $2 billion hedge fund. On a blind date in 2001, he met his wife, Catherine, a free-lance writer and editor. They married the next year, and she gave birth to Penelope, their first child, on July 6, 2002.

Growth in the Ribs

Penelope was 16 months old when she was diagnosed with neuroblastoma, a rare cancer that develops from nerve tissue and often appears first in the adrenal glands. By the time her parents noticed a growth under her ribs and took her to Mount Sinai Hospital, the disease already had spread to her lymph nodes, liver and bones.

Four days later, Ms. London delivered the couple’s second child, a boy named Oliver.

[Penelope]John London with his daughter Penelope outside their apartment in Manhattan last year.

Doctors told the Londons that Penelope had a particularly aggressive form of neuroblastoma and stood just a 25% chance of being cured. Over the next year, she underwent high-dose chemotherapy, radiation, a bone-marrow transplant and surgery.

A few weeks after the treatment ended, the family went on vacation to the Atlantis Paradise Resort, a hotel with a marine park in the Bahamas. They had just gotten off the plane when they noticed a lump on Penelope’s neck. They tried to ignore it and enjoy the vacation, taking turns holding her in the underwater tanks for hours to indulge her fascination with the giant stingrays.

Soon after they returned to Manhattan, they discovered the cancer was back. Radiation shrank the tumors in Penelope’s neck and skull, but the cancer broke through again after several months, in what would become a pattern. Each time Penelope’s cancer progressed, the Londons tried a new treatment — moving toward therapies earlier and earlier in human testing. Some treatments put her cancer into remission, others kept it in check for weeks, and some didn’t work at all.

Mr. London combed the Internet and connected via Web sites with parents of other children with neuroblastoma. When he heard of promising research, he phoned the physicians or scientists involved, pressing them about whether their work could benefit Penelope.

Several times, the Londons say, their doctors told them they were out of options and advised them to take Penelope home to enjoy the time they had left. “More than John, I was willing not to try anything else because I just wanted Penelope to be comfortable,” says Mrs. London. “But John just couldn’t do that. And many times, he was right. Penelope would not be alive today if it weren’t for him.”

“Penelope was still laughing those deep belly laughs of hers, still running around and looking healthy,” says Mr. London. “I just couldn’t give up on her.”

Not wanting to miss time with his daughter, Mr. London stopped going regularly to work at the Manhattan office of SuttonBrook. Running his hedge fund from Penelope’s bedside at home, he often stayed up all night devouring medical research papers. One day, sifting through 600 papers that were presented at a conference, he read about an antibiotic used overseas that appeared to help a child with neuroblastoma. Pediatric-cancer specialist Giselle Sholler wrote that the child’s cancer went into remission after being treated with the antibiotic plus chemotherapy. Dr. Sholler agreed to treat Penelope.

The combination therapy seemed to work, says Dr. Sholler, an assistant professor at the University of Vermont who had been studying the potential treatment in mice. The walnut-size lump over Penelope’s collarbone shrank to less than the size of a pea, Dr. Sholler says. For three months, as Penelope’s curly brown hair began to grow back, she played like any other child, dressing her dolls, making vanilla pudding with her older half-sister, Isabelle, and teasing the family cat, Charlotte.

“She had an incredible ability to bounce back,” says Elizabeth Raetz, a pediatric oncologist at NYU Medical Center who has been treating Penelope and advising the family since she was diagnosed.

Through the struggle, Mr. London grew close to the parents of other children with neuroblastoma. “I felt so alone in going beyond what the medical establishment wanted me to do, that the parents of other sick kids were the only ones I could truly relate to,” he says. He invested $100,000 in a fund that is paying for Dr. Sholler to test the antibiotic in combination with chemotherapy in a clinical trial. Dr. Sholler has enrolled eight patients in her trial and most have had their tumors shrink without many side effects, she says, although she cautions that the tests are still at a very early stage.

“John’s passion for finding a cure for this disease and his daughter made this trial happen,” she says. “And all of these children are seeing a better quality of life.”

Cancer Breaks Through

Last November, Penelope’s cancer broke through again. After unsuccessfully trying two other experimental drugs, Mr. London was particularly anxious when a parent emailed him in March about Neotropix’s therapy.

The experimental medicine is a virus that strikes pigs and appears, in early test-tube and mouse experiments, to attack certain cancer cells in humans. The approach is new and risky, Neotropix Chief Executive Peter Lanciano notes, because it involves injecting a virus into humans that they presumably haven’t been exposed to before. The drug is still in its earliest phase of trials for safety. It was tested in just six human beings over the past year. The company hopes to finish the first stage of testing over the next 18 months, giving the virus to another 49 patients, most with small-cell lung cancer.

Mr. Lanciano says that the week he took over as CEO nine months ago, the FDA put Neotropix’s trial on hold because the first patient died. Only after four months of testing and analysis was Neotropix able to resume its trial, having demonstrated that the patient died from cancer and not the therapy.

That delay was on Mr. Lanciano’s mind when Mr. London and his supporters began calling. The CEO says he wanted to help, but he thinks the drug is too early in testing to be used safely by a child. To give Penelope the dose that was effective in mice, he says he would have to multiply the top dose used in humans so far by 100,000 times. Normally drug companies are careful to raise the experimental dosage in small increments to detect side effects before they become lethal.

“The question is: Can we really help or would we do more harm?” asks Mr. Lanciano.

Mr. London argues this is a risk worth taking. “We’re not talking of testing an unproven drug in a child who is perfectly healthy and running around,” he says. “My daughter is already in so much pain and is so sick she can’t get out of bed. If anything has a prayer of saving her, how can you argue it’s not the right thing to do?”

Investors have put about $14 million into Neotropix, which was founded in 2003 by a former Novartis AG scientist. Last year, Mr. Lanciano, a former executive at several biotech companies, took the helm.

Mr. Lanciano and Neotropix board members have expressed concern that the FDA will force Neotropix to put its trial on hold again if Penelope dies. FDA officials called Neotropix and reassured the company that this isn’t the case, Mr. Lanciano says. A colleague of Mr. London who is an internist had approached the FDA and asked it to deliver that message.

Despite the verbal assurances, the CEO says he is still worried. “You never have the ability to wash your hands of any adverse events the patient has,” says Mr. Lanciano.

FDA officials, agreeing only to speak generally about the issue, said the agency would not hold a company accountable for the death of a very sick patient receiving therapy as a desperate effort.

“The FDA has good appreciation for the fact that we’re dealing with people mortally ill and this is a last-ditch effort,” says Richard Klein, director of the agency’s HIV program. The notion that the FDA would halt trials over a death in such circumstances is “more of a myth, or urban legend,” he says.

Nonetheless, “there aren’t any absolutes,” says Ms. Delaney, the FDA’s cancer liaison. “We can never say: ‘We won’t pay any attention to safety’ ” when a patient gets a drug.

The Neotropix board held several meetings on the question of giving the drug to Penelope, Mr. Lanciano says. At one point, the board called an ethicist for an opinion. Urged on by the London family, patient groups and politicians, including the staff of House Speaker Pelosi and Pennsylvania Gov. Edward Rendell, lobbied on behalf of giving the drug to the child.

On April 18, the Neotropix board decided not to provide the drug. Yet calls from politicians and Mr. London’s supporters continued, Mr. Lanciano says. Finally, four days later, a Sunday, Mr. Lanciano sent out an email, copying them all.

“Tremendous pressure has been brought to bear on all levels of the company” to try to get it to change its position, he said in the email. “We will not do so.”

Mr. Lanciano, 50, says he sympathized, having lost his wife several weeks earlier to cancer at age 51. He tried to get her in clinical trials for pancreatic-cancer treatments, but she didn’t qualify, he says.

“If I were that father and mother with a dying 4-year-old, I’d be doing exactly the same thing,” says Mr. Neff, the partner at the venture-capital firm that has invested in Neotropix. “There is no right answer,” he says. “But in a small company with limited financial resources and a high risk profile, you really have to reduce the risks to drug development.”

Mr. London is now trying a new avenue. A day after Neotropix turned down Penelope, a friend Mr. London met on a parents’ Web site told him about another company, Jennerex Biotherapeutics, also with a virus in the earliest phase of human testing for cancer. Mr. London reached the company’s chief executive, David Kirn, on his cellphone and the two spoke for an hour. Dr. Kirn, a cancer specialist, agreed to provide his experimental drug to Penelope if a hospital would agree to administer it.

“If you are in the position where a loved one is dying of a disease, it is impossible to understand how any company can withhold something potentially beneficial,” says Dr. Kirn. He says his company has raised $10 million so far, mainly from individual investors who leave medical decisions entirely up to him.

William Carroll, director of pediatric oncology at NYU Medical Center, said Saturday he’s trying to get permission to treat Penelope with Jennerex’s experimental virus at his hospital. He needs approval from several hospital committees that monitor clinical trials and biosafety because the treatment is a live virus. That process would normally take months.

Dr. Kirn is pitching in to make the case. “We’re asking hospitals to compress a six-month procedure into a week and that’s very difficult,” Dr. Kirn says. “You’re asking them to bless a plan with less than the full data that is normally available. But you’re asking them to do it for a heroic cause — to try to save a child.”

Running Out of Time

Mr. London knows the family may have run out of time.

Wearing pink pajamas in a ninth-floor room at NYU Medical Center last week, Penelope, frail and partly bald, tucked her favorite stuffed bear under her arm as she watched an Animal Planet television show about a sick walrus that was saved. She cried now and again, sending her parents rushing over. A bowl of half-eaten oatmeal sat on the table; Mrs. London asked a friend to make it with extra butter to try to fatten up her daughter. Mr. London’s computer was open to the Web site he uses to keep family and supporters updated about Penelope.

The Londons brought Penelope to the medical center Wednesday because her pain medicine wasn’t working. They thought she needed stronger drugs to stay comfortable. The plan was to switch her to methadone, a powerful narcotic, and take her home.

On Friday night, after Penelope had struggled for two days with the pain, her eyes lit up when her big sister, Isabelle, appeared in the doorway. The little girl, who hadn’t gotten out of bed in days, pulled herself up — batting away the outstretched arms of her parents — and wobbled over to sit on the cot beside her sister. Later, when Dr. Raetz, the oncologist, stopped by, she found Penelope, her arm shaking a little, putting the numbers of a block puzzle into the right spaces, not randomly but meticulously, in ascending order. “She’s a very determined little girl,” Dr. Raetz said.

“We go into this with our eyes open,” Mr. London said, talking in another room out of Penelope’s earshot. “The chance of anything bringing her back from the abyss now is very low. But the only thing I know for sure is if we don’t treat her, she will die.”

Mr. London and his wife say they are searching Penelope’s big brown eyes for clues as to how long she wants to continue to battle for life.

For now, says Mr. London: “We see she still wants to fight.”

In a New York minute

As Ronan slept last night, I found myself cuddled up on the single little bed that we have in the room with Woody. It is so tiny but I fit absolutely perfect in it snuggled up to Wood. At one point, he was rubbing my back while I was sitting up, looking at the floor. It was dark in our room and I just started to cry. He continued to rub my back and said something that I will never forget. He told me how sad he is that this is my life, that he only wanted to give me the best life ever. I wish I could say I came up with some uplifting words to say back to him, but I only nodded my head and continued to cry. We ended up whispering to each other about some things back and forth. I cuddled up on the little single bed with him for a while. He made me laugh by reminding me how when we were so young…and on our 30 day trip to Europe,while in London,the hotel we were staying at only had 2 twin beds. I had insisted on not sleeping in my own twin bed, but in his twin bed with him. It was cramped to say the least but all I wanted was to be as close to him as possible 24 hours a day. He said this was just like London and we both had a good laugh. Hardly London, but for a second I pretended like it was. Just the two of us, no worries, no cancer, no tears. Just us, blissfully happy, with not a care in the world. Seems like a lifetime ago. It’s nice to know after all of this, we can still go back there, even if it is only for a few minutes as our baby boys sleeps peacefully beside us in his hospital bed.

This morning I got a wonderful visit from a wonderful boy. Yes, I say boy, because he is only 26 and 26 feels so young to me, even though I am not too much older. I have talked about Ronan’s last roommate at Sloan on my blog before, Phoebe. The beautiful Phoebe, with the sparkling fighting spirit just like Ronan, and the bravest soul. During our stay at Sloan, while sharing a room with Phoebe, we became friendly with her cousin, Jonathan. He spent a lot of time with Phoebe having intense talks with her and teaching her all about life. Tricia, Macy and I all fell in love with the two of them. We have kept in touch and Jonathan stopped by this morning on his way to take the train to spend the week visiting Phoebe and her family at their home. It was so nice to see him and introduce Woody to him. He spent about an hour with us, and I got to hear all about the trip he just took to India,  before Ronan gave him the boot:) We had a good chuckle about that and Jonathon made Ronan laugh by telling him not to worry about it, that he was used to getting kicked out by ex-girlfriends, parents, etc;) He had Ronan is stitches even with how terrible he is feeling. It warmed my heart to see him and I sent him on his way telling him to give our love to Phoebe (who is doing wonderfully) and her mom, Ellen. I hope to see him again soon as he is now a friend for life. Tricia and Macy were both very sad that they were not here to see him too. That just means both of those girls have to come back here so we can orchestrate a reunion with Jonathan. Before we all do the NYC Marathon together once Ronan is well.

Woody went off and worked for most of the day. I sat and cuddled with Ronan and played Star Wars with him in his bed. We sang a lot of songs and I got him to get up a little bit so we could look out the window and shoot the snipers on the roof of the NYC buildings. He is still hurting and now is saying that everywhere hurts. I am doing my best not to panic and hoping it is just he hospital blues. We had a visit from the floor doctor today and his team as they were doing their rounds. It’s the first doctor here the I have met that I immediately didn’t like. He was condescending to say the least. As soon as he left, I gave Woody “the look” and he started cracking up laughing saying he knew I was going to bitch about him. I think my exact words were, ” I want to punch that guy in the face.” Woody agreed. The guy was a douche and I did not appreciate the way he was talking to Ronan, Woody or myself. He used some really stupid analogy on Woody when Woody asked if we could be discharged today. We both knew that the answer was going to be no, due to the pain control, but the way the doctor went about telling us no, was not necessary. We are not idiots and he could have said it a little more nicely instead of treating us like we were morons who came so far away from home. All the way from the Wild Wild West of Phoenix, AZ, where apparently, we have not evolved. I did also did not appreciate the way he made us feel like radiation and chemo was not going to do the trick for Ronan’s pain. We were told not to expect the pain to ease up until the end of the week. It is only Monday, you dick. Give some very scared parent’s a little ray of hope instead of going straight into what our options are if this doesn’t work. I don’t want any other options now, because this is going to work. I hope I never have to see that doctor again because I may just give him a swift kick in the balls.

Dr. Modak came by just as I was freaking out in my head over Ronan’s pain. He asked how he was doing, I said not well, and I told him we were very worried. He reassured me that everything was going to be o.k. and that the radiation was going to take some more time to kick in. I straight asked him if he feels like we can still get this under control. He told me without a doubt. Dr. Modak would not lie to us; my faith is in him completely. He said the combo of the chemo and radiation will work. We will take care of this little bump in the road and get Ronan back on track. I have no doubt about this.

After Woody returned to Sloan after a long day/evening working, I ran out to go back to the RMH to shower and gather up some new clothes. I was tempted to go on a run, but it was already 9:00 p.m. here and I wasn’t feeling up to being dangerous tonight. I had Marisa’s little voice in the back of my head chirping away about running in Central Park at night. I was way too tired anyway. Hopefully tomorrow I’ll sneak in a some time and get a run in. Lord knows I really need it even though my energy level is shot due to hospital life. It really takes a toll on me emotionally and physically, no matter how fun we try to make it.

Back at Sloan now and all is peaceful. Ronan is sleeping, Woody is on his computer, and our adorable roommates are listening to some show on their computer and laughing. The girl we are sharing a room with is a senior in high school and she has a girlfriend spending the night with her tonight. Her sister has been here every other night. They are adorable Jewish girls and I have a had a blast watching them celebrate Shaushan Purim all last week and it ended last night. They have been dressing up in costumes, laughing and talking all about their religion, beliefs, high school, etc…. It has been very sweet and uplifting. Never mind that one of the girls is very sick with cancer. Has not dampened their spirits at all. It is roommate heaven, as far as having to share a room goes.

It’s officially very late here… and I am a sleepy girl. Please continue to send Ro your strength and love…. please let his pain subside. And New York Miss Macy…. no more tears tonight my love. He is going to be fine. I love you.

G’nite all you beautiful people. Sweet dreams to  you all.

xoxo

We’re not married…. we’re still dating;)

I wish I could tell you tonight that we have our answer. But I can’t. Woody and I both left the house on the same page this morning, thinking we knew which approach we were going to take. That all changed after meeting with Dr. Adams, the head of Stem Cell Transplant at PCH. I should have known the answer was not going to be so easy. Woody, Fernanda, and a I sat across from Dr. Adams and Woody did all of the talking. Fernanda sat and wrote notes and held my hand; I sat, listened, absorbed, and cried. At one point I looked up and told everyone I was just trying to do my best not to throw up everywhere. Dr. Adams looked at me and said she didn’t blame me, she was devistated that she had to be having this conversation with us. But, she said she still feels like Ronan can be cured…it’s just going to take a little more work than we would have liked. She said we have a ton of options available but unfortunately, nobody knows the right answer. The decision we are going to have to make is going to have to be based on all the data we collect and a gut feeling. Those were her words exactly. I told her I’d be gut feeling, and Woody could be the data:) Sounds like a perfect match to me. What Dr. Adams would like to see is us do 2 more rounds of a different type of  chemo here, than rescan Ronan and make a decision after that. She does not want us to jump head first into anything. Woody and I both agreed that this sounded like a good idea to us as long as it won’t close any doors as far as other options go. We are waiting to hear back from Dr. Kusher at Sloan to see if he is o.k. with this. We don’t see how this would hurt Ronan at all, if anything everyone seems to think we can get rid of some more of his disease this way.

There are not many people in the world that I would trust with the life of my baby, but Dr. Adams is one of them. I don’t have a super personal relationship with her for obvious reasons, but I don’t need one to know that she is a very special woman. She is brilliant beyond belief, compassionate, open minded, and has dedicated her entire life to this. She truly cares about each and everyone of her patients. She has this amazing aura around her and I feel it whenever I’m in her presence. After we left her office, Fernanda and I went out into the main waiting room to take care of some business. Fernanda looked at me and said, “I still have goosebumps after being in that room with that woman.” Fernanda felt it too. This woman is a gift to us and I want to keep her involved in Ronan’s care for as long as possible.  I fully trust her and respect her opinion so much. She wants to give Ronan the best shot possible is willing to do whatever she can. She was very hopeful because Ronan has responded so well and as I said before, she just thinks he needs a little something extra. Staying here and starting chemo would give us more time to figure out our exact plan. I hate just to jump right into anything if we can take baby steps instead to really make sure what we are doing is right. Fernanda had Dr. Eshun’s assistant get all of Ronan’s scans out to about 6 different doctors. We will take all of the opinions we can get right now. This is not the end of the road my friends, not even close. This is the beginning of a new path we are going to take to get Ronan well. I am embracing it with open arms and know it will be the right decision, when the decision is made. I trust in the higher power who is in charge of this…..whomever that may be as I believe there are many forces behind getting Ronan well.

Once again I am in awe of my husband. I sat today and watched him fire out questions to Dr. Adams that I think she was even surprised to hear him ask. He knew the names of all of the studies, the side effects, what things would open doors and what would shut doors. It is pretty amazing when you can watch someone like Dr. Adams be so impressed with a father and his wealth of knowledge. I wish I could have been of more help, but I cannot seem to detach myself from the emotional side of all of this. I don’t know what I would do without Woody. I said to Tricia yesterday, “Could you imagine if I were married to a moron and going through all of this?” There is no way I could get though it. I am so thankful I am married to such a brilliant man. I love you, Woo <3

We still know Ronan is going to beat this but as I said before, he is going to do it his way. We will get this figured out but it is going to take a little bit of time. Nothing is set in stone and I loved it today when Fernanda said in her beautiful accent, “Honey, I love that you’re not married to one idea, your still dating!” I’ll never forget how her words made me feel today. I’ll never forget her sitting in the clinic with me and seeing her tears over something I had shown her that I carry with me everywhere I go…. her Christmas card picture with all of her 5 beautiful children on it. I feel like it brings me luck and it will help to guide me. It’s the little things that mean so much to me now. Whether it be the Claude necklace I always carry with me, my four leaf clover necklace that I never take off, Pam’s bracelet that she gave me that I also never take off, or Fernanda’s Christmas card. All of those things bring me peace and although they seem little and insignificant, they all mean the world to me.

Today was a long day to say the least. I have taken my sleepy medicine so I can actually sleep tonight. If I miss a dose, sleep does not happen. I’m o.k. with this. It won’t be forever, and I know how important it is for me to get some real sleep. My dreams are still intense and sometimes they are good, and sometimes they are bad. Working on tricking my mind into making my dreams as peaceful as possible.

Goodnight my sleepy friends. Goodnight Moon. Goodnight my sweet baby Ro, Liam, Quinn and Woo. Goodnight my Fernanda… I will meet you in my dreams for cocktails, on a beach, far away from all of this. I love you.

The dawn is breaking
A light shining through
You’re barely waking
And I’m tangled up in you
Yeah

I’m open, you’re closed
Where I follow, you’ll go
I worry I won’t see your face
Light up again

Even the best fall down sometimes
Even the wrong words seem to rhyme
Out of the doubt that fills my mind
I somehow find
You and I collide

I’m quiet you know
You make a frist impression
I’ve found I’m scared to know I’m always on your mind

Even the best fall down sometimes
Even the stars refuse to shine
Out of the back you fall in time
I somehow find
You and I collide

Even the best fall down sometimes
Even the wrong words seem to ryhme
Out of the doubt that fills your mind
You finally find
You and I collide

You finally find
You and I collide
You finally find
You and I collide