This is a fair question, all the more if you take a glance at her now even longer CV. It’s as if she has an extra hour every day; year in, year out. ‘A thesis in my dissertation was that you never lack time, but you may lack sleep! I gave birth to my youngest when I was doing my PhD research. The day after I gave birth I was already back to work, while I lay in bed. The baby lay in the cradle next to me. My mother said I was crazy. “He’s asleep, isn’t he?” I replied. I didn’t see the issue at all.’
Neeltje Steeghs (41) lives with her husband and their three sons (12, 14 and 16) in Leiderdorp, a village in the province of South-Holland. In addition to being head of the Phase I/Pharmacology department, Steeghs is also a medical oncologist (which she trained for at the same time she was doing her PhD research) and trained as a clinical pharmacologist at the Netherlands Cancer Institute. She also holds various ancillary positions in her field. Neeltje studied biomedical sciences and medicine at Leiden University. ‘I was looking for a degree programme with a strong social component, and it is very important for me to use my brain,’ she describes her choice. ‘I want to solve puzzles.’
This motivation also determined her choice for oncology. ‘I didn’t want to become a GP, because I didn’t like the idea of losing all the most interesting cases to a specialist.
I considered specializing in child oncology, but I was held back by the complexity of childhood cancer; I saw how the parents, who made all the decisions, often wanted to go further with the treatments than the children themselves. Oncology is the fastest developing and most innovative medical discipline, and there is still so much to gain through research,’ she explains.
The Pharmacology department mainly works on what it calls ‘Phase 1 studies’. They are currently conducting some sixty such studies, which are distributed among five physicians, while a large group of specialists supervise the patients and the studies. Steeghs herself is leading roughly forty of these studies. ‘We’re still working to distribute them more efficiently,’ she apologizes. ‘Two of the physicians have just joined us, and we didn’t want to throw them straight into the deep end.’
‘A Phase 1 study involves testing a new drug, or combination of drugs, in humans for the first time,’ she explains. ‘At this point, you’re not so much interested in whether it works, but rather in how the drug should be administered: what dose and at what frequency? And what are the side effects? We hope to find a dose that is tolerable, and hopefully see at least a hint of efficacy.’
Finding the right dose involves precise fine-tuning, and Steeghs continually customizes the medication to each case. She is currently leading a high-profile study that will hopefully demonstrate the logic and efficacy of customized medication programmes. ‘About half of the patients are not getting the right dose at the moment. That has to improve,’ she says.
‘Let me give two patients as an example. They were both getting 800 milligrams of pazopanib – the prescribed dose. One patient was taking the drug for a soft tissue tumour, the other for kidney cancer. The first patient suffered from so many side effects after the first two weeks that she had to be admitted to hospital. She turned out to have an extremely high level of pazopanib in her blood. Our first thought was to stop the tests; the risk was too great. Only, this drug offered the patients the best chance of improvement. When we persevered and reduced the dose to 200 milligrams every other day, she still had an ample concentration of the drug in her blood, but was now able to tolerate the dose.’
‘The other patient continued to have low drug levels,’ says Steeghs, ‘so we gradually increased the dose. We eventually raised it to 1800 milligrams a day, with no further side effects, while the drug reached exactly the same concentration as the other patient.’
Steeghs shakes her head when asked if the two patients survived. ‘There’s no holy grail,’ she says. Steeghs explains why their prospects were poor to start with. ‘The life expectancy for patients with a metastatic soft tissue sarcoma is about twelve months, for renal cell carcinoma it’s a year and a half. Medication can prolong life and/or mitigate the effects of a disease, but without a cure, the tumour cells will at some point become resistant.’
The patients whom Steeghs and her colleagues work with have stage four cancer. That usually means metastases, and no chance of recovery. So, the Phase I/Pharmacology department offers these people a glimmer of hope, but no more than that.
‘That makes the work really intense. It’s worst when I have to conclude that I have nothing more to offer a patient, especially if I have built up a long relationship with them and then have to tell them there are no further treatment options. I also feel terribly for the nurses, and it’s part of my job to comfort them and help them through this process.’
‘But it’s also intense when everything falls into place. One patient from Limburg has been coming here for nine years now. She gets the full treatment every time: biopsies, blood tests, medication... and all without a single problem. She has the hereditary breast cancer gene and takes olaparib. She’s been in remission for nine years.’
‘She lost her husband earlier on. Her son told her: “Mum, I can’t lose you too.” Her older sister, who also has the gene, was not healthy enough to undergo treatment. She died. But this woman has since seen her son sit his final exams, go on to university, and now she’ll be attending his wedding.’
The story of the Limburg sisters is telling; not just anyone can participate in a Phase 1 study. ‘It’s very intensive. Biopsies, scans, blood tests, dose adjustments, the side effects, the uncertainty – only ten percent of what I give the patents works: people have to be in healthy condition to be able to withstand all that. They need to be fit enough in mind and body to make bold decisions about their own lives. They are confronted with end-of-life issues: how far do they want to go?’
‘Yes, sometimes patients get very angry when they are not admitted to a study. We have created an increasingly manufactured world, and more and more people think that life can be manufactured in the same way.’
‘But happily, most of our patients are satisfied. Of course most of them hope that the experimental treatment will work, but at the same time they’re well aware that it may not. People may also have a very altruistic motive: if the treatment doesn’t help them in the end, it may yet help others. Some are very happy just to get four extra months, while others think: this is too hard, I can’t keep doing this.’
‘Phase 1 studies are strictly regulated, but sometimes the number of safety checks is really over the top. Obviously, patients who are taking a new medicine should not become pregnant, but it makes no sense to make a patient take a pregnancy test every week. But we have to, because otherwise we’re liable to face a claim from the US. Or the requirement that a patient has to have an empty stomach to take the new drug – by the time we’ve done all the tests and safety checks in the hospital it might be six hours later; that’s really asking too much of the patients.’
‘But at the same time, the cooperation with the pharmaceutical industry has many benefits, including financial. Our researchers can’t do it all on their own; that wouldn’t be affordable.’
Sometimes one of her own studies at the Antoni van Leeuwenhoek hospital – one that started off as a promising laboratory experiment – eventually meets with success, or even becomes a fully-fledged treatment. Those wins are what keeps Steeghs motivated. ‘You know what’s gone into it and who worked on it, and you know that what we’ve discovered has real potential. That’s something we can all be incredibly proud of.’
Courtesy of Noordhollands Dagblad.