Saying No to Penelope - WSJ article about neuroblastoma

Saying No to Penelope

Father Seeks Experimental Cancer Drug,But a Biotech Firm Says Risk Is Too High

May 1, 2007

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.

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.

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."

Write to Geeta Anand at geeta.anand@wsj.com

URL for this article:http://online.wsj.com/article/SB117798196751887629.html


Ryan - angel 4/26/07

This disease sucks. Ryan only got home (Albany, NY) last night from Houston (MD Anderson) where he was being treated. Visit Ryan's site



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#7 Complete

Max is finished with round seven of his chemotherapy and is doing great. (I can't say enough good things about that g-tube! Amazing what good nutrition can do for a kids overall well-being.)

While finishing up his last day of chemo this week we were visited by a pair of storytellers who work at the hospital. They were very funny and told us (acted out) a couple of stories. Max actually set aside his Leapster and joined in on the fun shouting directions and laughing.

Our weekend has been very nice. Saturday morning we finally took the Rokenbok (loaned to us by some great friends - thanks!) and set it up in the livingroom on the train table. The kids are having a great time playing with it. Even Nic enjoys putting cargo-balls in the trucks for Max and Hannah to dump. Max has figured out how to drive those trucks really well. Hannah likes to fill the monorail trailer with cargo-balls then drop them on other trucks from high above.

Andy and Max left this morning on a run to the local nursery to pick up some flowers for the yard since it's Earth Day. Max also wants to find a fresh packet of pumpkin seeds in hopes that we can grow a pumpkin for Halloween. The kids are currently growing a batch of peas behind the playhouse just waiting for the day they produce. Hannah decided to stay home and explore the yard in her own fashion. I think chemo week makes Hannah miss home and homelife. Yesterday she stayed home, too. Laid in the sun, decided to wash the playhouse, got her clothes wet and ended up naked in the backyard. Ahh, to be a kid again!

Tonight we start the fun gcsf-shots again. I have to get to a store today and buy a Bionicle for Max's shot prize per his request. I have to tell you how well he does with those shots. He and I have our own jobs each night for the shots and he gets through it with no tears. He's truly amazing.

Tomorrow begins a new week and back to the grind of fitting in as much school as possible for Max with scheduled clinic appointments twice a week. Monday he goes in for vitamin C and zometa infusions; Thursday just vitamin C. Oh, and don't forget blood draws and possible blood transfusions. There's a lot of in-the-car-time for Max and Nic every week.

Until next time...


Pulitzer Prize photos featuring boy with neuroblastoma

Series of photos taken of Derek Maden and his mother Cyndie French during his 11-month battle against neuroblastoma. These photos won the photographer a Pulitzer Prize.


All Around Update + Chemo VII

Wow... Max started his 7th round of chemo today - on time I'd like to add. The booster GCSF shots he received over the weekend pretty much cinched it for him. Max is feeling good and doesn’t have too many complaints right now. It’s great to see him with a little head of hair and displaying some energy. Not really what you’d expect from someone starting their 7th round of chemo. Max and I had a pretty good day at the hospital from 8:15 to 6:15 (Monday's are long!) but we're no worse for the wear.

Max just had a CTscan of his feet and knee last week as well as a whole body MIBG (bonescan). It doesn't appear that there are any new hot spots (from what my untrained eye could see on the MIBG). There is a singular spot on his spine still, but nothing lit up anywhere else. The CTscan results came back with nothing. Max had been complaining about pain on the bottom of his heels and in his knee/leg area. We have reason to believe that his heels were hurting because he's been way more active (running, playing, etc.) since he began his tube feedings. The cause of his knee pain could be the same, but could also be attributed to one or more of the medications he takes. It's great to have a doctor who's willing to react as fast we need. The emotions of having a child with this cancer can be overwhelming and the help we get from Max's oncologist is one less burden. Thanks, Dr. Roberts!

Max’s g-tube is apparently working. We checked in for chemo today and found that his weight has gone up to 17.1 kg from 15.9 kg when he had it inserted three weeks ago. "Woo-hoo," as Andy so eloquently put it via text message! We are also going to change his appetite enhancer back to Megace. The periactin (sp?) we tried didn’t do anything, so we’re giving the first one another go around. Started it tonight.

Max’s hair is partially grown in and looking very fuzzy – like a duckling. I may need to take him down to the shop for a little buzz to even it out. I did notice some hair on the pillow in clinic today, so maybe I'm jumping the gun on a haircut!

I took Hannah and Max down to the model train museum this weekend. Usually Andy is in charge of this outing, however he had just taken Max there the weekend before so I took the reins and we headed down to Balboa Park for Western Days at the train museum. The kids dressed up in their western finery. Max in his blue plaid Wrangler shirt with slick black leather vest, and Hannah in her pink suede, fringed vest and matching skirt. Don’t forget the hats! We ended up in the fun, loud train room - O gauge - where one of the gals, Amy, who works there noticed Max with his obvious ‘currently-in-chemo-treatment’ look and struck up a conversation with me. She introduced me to Jon Everett, O Gauge Club President, and they offered Max the opportunity to come down on a Tuesday and run the room (control the trains)! F-U-N! Max is stoked and can’t wait for the next Tuesday we can make it down there.

Max and Hannah's school has a KidsKorp group that meets after school once a month. This month they've decided to honor Max and Hannah. They're going to read a beautifully written book called "I'm a Superhero" by Daxton Wilde (and his mom). It's a four year olds' interpretation of fighting cancer. The kids at the meeting will be able to ask questions and Hannah will be there to help answer them. They will make orange bracelets for all the kids in school to wear on a special day just for Max. (date tbd) This will really be a great opportunity for Hannah to feel involved and important during this time where she's a "second-rate-sibling" (to steal a phrase from Syd Birrell).

If you haven't already checked over on Max's Kid Friendly Site, be sure to. Eight year old Cousin Alaina spearheaded a recycling effort at her school and made $600 for the playroom at the hospital. Wow, again, Miss Alaina, and thank you!

A huge thank you going out to everyone bringing over meals and to Kristen and Lori for organizing this project thebelskys@earthlink.net or lorigood@san.rr.com. Getting home tonight at 6:45 and being able to just sit down and eat is such a blessing. You people are great and we really, truly appreciate you! (PS - we're covered this week ;-) contact Kristen or Lori if you'd like to be included in their future emails.)



Kendall an angel

Kendall (post below) passed away this evening at 8:30pm CDT. That's how quickly this beast works. Send some good thoughts his family's way (he has a twin, Zachary). This kid was a warrior.

Three kids that could use some good thoughts thrown their way

Kendall http://www.caringbridge.org/ny/kendall/
Penelope http://www.caringbridge.org/ny/penelope/
Ryan www.caringbridge.org/visit/ryanmccormick

Also, both Max and Sam have been complaining of knee and leg pain off-and-on lately so they're both getting scanned ASAP to see what's going on. Max's scans are tomorrow (CT) and Friday (MIBG). Sam's are the following week I think, but I'm seeing his dad tonight and will find out definitively.


Top Ten Signs You’ve Been Fighting Neuroblastoma Too Long

Shout out to Margo for coming up with true comedy (that which is funny and makes a point that otherwise would be difficult to make without humor).

10. Every time your child gets a fever you hope it spikes to 101 or higher.

9. You’ve ceased to register the shocked faces at preschool when you off-handedly say, "Oh we can’t make it, we have chemo that day."

8. You’ve started inviting the nurses over to dinner

7. When you are at the ENT with your other child talking about removing his tonsils and the doctors says, "It’s surgery you know, it requires general anesthesia," you involuntarily go "Pfff."

6.When your child is diagnosed with pneumonia, you hope it’s the viral kind on the off chance pneumonia is an oncolytic virus that kills neuroblastoma cells

5. You can spell "pneumonia" and "oncolytic virus"

4. You don’t even flinch at throw up at a birthday party and help clean it up even when it’s somebody else’s child.

3. You can sleep through a stem cell transplant (stole that from the Londons)

2. When your child says something hurts you hope he or she has broken a limb somehow.

1. You have a hard time drumming up sympathy for Elizabeth Edwards and get ticked at all the cheery articles on how great it is to live with cancer these days.


General Grevious Gets Gushed

Tuesday Morning
7:00am - Max is a trooper. He's still not eating much but we'll pick up a prescription for a new appetite enhancer this afternoon at clinic. Breakfast was a flop, however, he powered down almost all of his pills (keep this in mind).

9:00am - Nic has an appointment with the peditrician. While I'm checking in I get a phone call from Hannah & Max's school. Its the school nurse: "Hi, Mrs. Mikulak. Max just threw up in class. He's here with me in the nurses office." Ok, um... I can be there in about 30 minutes. Is he feeling okay now? "Yes, he seems to be in good spirits." Ok, I'll be there as soon as I can.

So I get through Nic's appointment: he's a little anemic which could be caused by a virus or ??? And it appears he has a hernia in his diaper area if you know what I mean... So I just need to schedule an appointment with the surgeon, Dr. Hilfiker, who happens to be Max's surgeon, too. (I do not have time for two sick kids. What are these children thinking?)

Back to Max: we get to school and Max is reading happily along with the nurse through a big book of birds. He's happy as a clam and ready to go back to class. I excuse myself and trot down the hall to speak with his teacher, Ms. Weitz, to find out what happened: Today was Max's turn for the Secret Sack (show and tell). He brought his brand new Star Wars Lego General Grevious figure with four light sabers and the empty box showing the cool Lego ship that he has at home. Apparently he got a little excited about showing his new toy and nervious about talking in front of the class and promptly threw up IN the lego box. Ms. Weitz found herself impressed with his throw-up know-how. Mommy quickly remembers that he ate nothing this morning except a handful of pills. Hmm...

The good news is that he went back to class and felt fine the rest of the day.