Posted 4/14/2019 6:44 AM (GMT -5)
You and your Dad might follow-up on research currently underway changing drugs when PSA goes up. This excerpt is from an April 2019 Wired magazine story (A Clever New Strategy for Treating Cancer, Thanks to Darwin) the first small study to test this adaptive therapy approach off the ground, recruiting Robert Butler and a small group of other men with advanced prostate cancer. Butler’s oncologist explained to him how it would work. He would remain on the Lupron he’d taken for years, and each month he would go to the hospital to get his PSA level tested, to judge whether his prostate tumor was growing. Every three months, he would get a CT scan and a full-body bone scan to watch for disease spread. Whenever his PSA level edged above where it stood when he entered the trial, he would start taking the more powerful Zytiga. But when his PSA level fell to under half of the baseline, he could go without Zytiga. This is appealing because Zytiga and drugs like it can cause side effects like hot flashes, muscle pain, and hypertension.
The Moffitt approach also promised to be far cheaper than taking Zytiga continuously. When purchased wholesale, a one-month supply costs almost $11,000. Butler had health insurance, but even so, his first month’s supply each year would set him back $2,700 in out-of-pocket copayments, and $400 a month thereafter. Going off the drug whenever his PSA level was low would translate to huge cost savings.
“Conceptually it’s a beautifully simple approach. He’s turning cancer into a chronic disease.”
Butler was participating in a so-called pilot trial, which was less rigorous than a large clinical trial, because it didn’t randomly assign patients to receive the experimental or standard treatments. Rather, the study relied on a group of patients treated outside the trial as well as results from a 2013 paper on Zytiga to come up with a benchmark for how patients typically fare when receiving continuous dosing of the drug.
When the early results of their new trial trickled in, the Moffitt scientists were gratified and relieved. Ahead of the trial, “we were, to be honest, terrified,” Gatenby says. The benefit of adaptive therapy appeared to be huge. Of the 11 men in the study, one left the trial after his disease spread, but most were living longer than expected without their cancer progressing. Men getting continuous dosing of Zytiga go a median of 16.5 months before the cancer becomes resistant to the drug and spreads. In comparison, the median time to progression for the men receiving adaptive therapy was at least 27 months. Moreover, they were on average using less than half of the standard amount of Zytiga. Joel Brown, an evolutionary ecologist and one of Gatenby's collaborators, said the team felt a moral obligation to get the word out: “The effect was so big that it would be unethical not to report it immediately,” he says.
They published a report in 2017, far earlier than anticipated, to a generally positive reaction from prostate experts—particularly because it suggested a way that people with cancer might live longer with less medication. “If you can reduce side effects, I think that’s fantastic,” says Peter Nelson, an oncologist who studies prostate cancer at the Fred Hutchinson Cancer Research Center in Seattle. “Conceptually it’s a beautifully simple approach.” Jason Somarelli, a biologist at the Duke Cancer Institute, calls Gatenby a pioneer: “He’s turning cancer into a chronic disease.”
Butler, who is 75, has gone for long periods off Zytiga—with stretches lasting as long as five months. “I’m now the poster boy, they say,” Butler says. He’s one of the best responders in the study.
69 yrs., marathon runner, 44 3D-CRT/IMRT Radiation delivered via 3D-CRT in 1.8 Gy minimum dose fractions to a total of 79.2 Gy., 3.2.19 PSA .04 T.Tot 440, 10.5.18. PSA 0.12, 8.12.18, 1.42 June 18, 2018 (Lupron 5.21.18 & 8.15.18), 12.7 May 2018, 13.7 Jan. 2018, 2.1 May 2012 TTot 686 ng/gl. SpaceOar 9.6.18, testosterone <.7, 8.15.18, Tot Mayo 19 ng .17 testosterone Free 6.18.18, May 21, 2018 T. Tot 686ng/dl; Gleason 3+4=7 involving 15% of the right apex and 15% of the right mid, 3+3=6 prostate cancer involving 5% of the left base. Pathology interpretations by John Hopkins, UNM Cancer, and SF Path 3+4=7 or 4+3=7 MD Anderson Proton Center w/o %. T3 MRI w/ contrast 1.8 lesion left side 5P, Neg. Bone Scan. Prolaris test 3.5 consistent with intermediate and a PTEN test negative. Father PC age 78 RT & ADT now 94 yrs.