After a cancer diagnosis, a clinical trial offers hope

In 2015, when Graeme McLean was diagnosed with advanced prostate cancer, he was utterly devastated. Then an MRI scan delivered an even bigger blow.

“The MRI showed spots on my right and left ribs and one on my pelvic bone, which meant the disease was metastatic – it was out of the prostate gland,” says McLean. Biopsies revealed the cancer was aggressive, and he was given two to four years to live.

“Once the cancer is out of the gland there’s no point operating on or treating the gland,” says the now 81-year-old resident of Orange, NSW. “To put it mildly, I was rather upset.”

That’s when McLean was referred to Dr Robert Zielinski, a senior staff specialist medical oncologist and director of clinical trials at Orange Base Hospital. Dr Zielinski, who is also a lecturer at Western Sydney University, sees patients for whom other treatments, such as radiotherapy or surgery, have failed, or who have prostate cancer spreading into their bones.

“I’ve got about 300 patients with incurable prostate cancer. But it can be quite an indolent cancer, so even though it’s incurable, it can grow quite slowly,” Dr Zielinski says. “However, there is a subset of patients who have a much more aggressive disease who desperately need novel therapies.”

Nevertheless, McLean arrived at his June 2015 consultation with Dr Zielinski with a heavy heart. He was convinced that at 77 years of age he was very unlikely to get on a trial for any new medications that might improve his prognosis.

To McLean’s surprise, Dr Zielinski advised him he was eligible to participate in a clinical trial for a promising new prostate cancer drug. McLean leapt at the opportunity.

Prostate cancer is the most common cancer for men in Australia, with around 20,000 new cases a year. Many men are successfully treated and around 95 per cent are still alive after five years. But for around one in five men, the cancer spreads throughout the body, and in the unluckiest 4%, like McLean, the cancer has already spread by the time it is first detected.

Once prostate cancer has reached this stage, removing it surgically is no longer possible, the next option is so-called androgen deprivation therapy (ADT), which means starving prostate tumour cells of the testosterone they need to multiply and spread.

“It’s a very hormone-driven cancer,” says Dr Zielinski. “If you take testosterone away from men with prostate cancer, their cancer shrinks rapidly.”

This can be done by removing the testes, but it is more commonly achieved through drugs that block the production of testosterone. “It is an incredibly effective treatment, but it is unfortunately, associated with a lot of undesirable side effects for a man,” he adds. Side effects can include fatigue, male menopause, hot flushes, mood swings, and irritability.

Nevertheless, such drugs offer a lifeline to patients – and this new drug was one of the newest and potentially most effective available.

As part of a clinical trial led by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, McLean became one of 1125 men given injections of testosterone supressing drugs, and a daily anti-androgen tablet of a new drug or one of several similar older drugs already on the market.

The study is a vital ‘phase 3’ clinical trial, which sees a new drug tested in potentially thousands of patients and compared to current standard treatments. At this stage, drugs are already known to be effective and have previously passed through ‘phase 1’ and ‘phase 2’ trials, which involve much smaller numbers of patients. 

Since McLean started on the trial, he’s has had regular appointments with Dr Zielinski, and the men have come to know each other well. “We live in a country town, so his kids go to the same school as our grandchildren, and he lives diagonally across from where our son is building a house,” McLean says.

Dr Zielinski adds: “There are rollercoaster days and periods, but we’ve got a wonderful relationship, and we talk a lot about his kids, family, travel pursuits, and hobbies.”

While half of the patients in the trial were treated with an existing ADT drug, McLean was one of the lucky participants to receive the new drug, as the preliminary, three-year results from the study have recently revealed.

Reported at the American Society of Clinical Oncology meeting in Chicago on 2 June, the results showed that the new drug reduced the overall risk of death by about one third. After three years, 80 per cent of the men receiving it were still alive, as opposed to just 72 per cent of the patients taking existing, standard prostate cancer medications.

For McLean, it’s difficult to put a value on what the drug has given him. When he began treatment he was in despair, but after finding his PSA level (a marker of prostate cancer in the blood) fell to zero and stayed there, he began to hope once more.

“I became more and more excited… It’s meant reaching four years, which was supposed to be the end of my life,” he says. “When I made it to four years, I gave Rob a hug, and I think he thought I was going to kiss him.” 

“I met Graeme when he was first told that he’d developed an incurable prostate cancer,” Dr Zielinski recalls. “So, you go from that first meeting where there is immense sadness and tragedy… [to] this burst of positivity and happiness and emotion that just oozes out of him… he often tears up, and he thanks you dearly.”

The new drug does not cure prostate cancer. McLean’s PSA levels will one day rise once more, but until then he and his wife are in the process of “spending the kids’ inheritance” and planning overseas travel, he says. He also feels proud to have helped in the development of a treatment that could save other lives.

The results of drug trials are often negative, so to be involved in the discovery of a practice-changing medicine “is a fantastically warm and exhilarating feeling,” says Dr Zielinski. “You’ve really achieved something long-lasting with your team of trial nurses and of course the patients. It’s great telling patients: ‘You’ve helped define the new standard of care for prostate cancer’. Seeing the patient’s faces light up is wonderful.”

“That’s what clinical trials do. They provide some hope to the patients who think they’re beyond hope,” he adds.

By John Pickrell