With an estimated worldwide occurrence of only 200 patients each year, adrenal cancer is so rare that most endocrinologists will never have to deal with it. While this paucity of cases makes drug trials difficult, potential new treatments are generating hope.
Of all the cancers that strike the body’s endocrine system, adrenal cortical carcinoma (ACC) is one of the rarest and toughest challenges. In fact, the actual number of diagnosed cases of ACC in the U.S. is unknown, according to the American Cancer Society, which places the estimated number of newly diagnosed patients each year as low as 200. Other estimates, however, suggest a higher incidence of one to two per million per year.
Detecting adrenal carcinomas early is difficult and they are often quite large when diagnosed. For adult patients with ACC, it is a very aggressive malignancy with an often poor prognosis. Approximately 40% to 50% of newly diagnosed patients present with stage IV with metastases. The five-year survival rate for patients at this stage is about 10%.
- There is hope on the horizon for new therapies for adrenal cortical carcinoma.
- International collaboration helps to understand the biology and genetics of the disease and to cooperate with each other and perhaps with pharmacologic companies to engage in substantive clinical trials.
- Although the numbers of patients with adrenal cancer may be small, patients around the world are finding their voice and becoming advocates for their care.
But there is hope on the horizon for new therapies for ACC. Last October, the University of Michigan, Ann Arbor, hosted the 5th International Adrenal Cancer Symposium and leaders were left encouraged.
“What we learned from the symposium is there’s always hope,” says Gary D. Hammer, MD, PhD, director of the Endocrine Oncology Program at the University of Michigan. “New treatments will evolve and I’m certain of that.”
The 2015 symposium followed previous global conferences held in Paris and Wuerzburg, Germany, and the University of Michigan hosted the initial symposium in 2003. The symposium welcomed specialists from multiple medical disciplines who are involved in the care of adrenal cancer patients, including endocrinologists, surgeons, radiation and medical oncologists, and radiologists.
“The purpose of all those symposiums was really to share knowledge, develop collaborations, and push the science into new collaborative research,” Hammer says.
“Clinical trials are partly limited by the patient population that you can get engaged in a trial. And for a rare disease where most doctors in the United States have never seen a case, or if they do, have only seen one case in their career, it becomes essential to collaborate for the science and delivery of care.” — Gary D. Hammer, MD, PhD, director of the Endocrine Oncology Program, University of Michigan, Ann Arbor
The Standard of Care
For newly diagnosed patients, the standard of care for the disease, like most cancers, includes surgery, radiation, and chemotherapy. Treatments vary, but patients are most often given the chemotherapy drug mitotane, the only drug approved by the Food and Drug Administration for treating the disease. Mitotane blocks hormone production by the adrenal gland and also destroys both adrenal cancer cells and healthy adrenal tissue.
Neoadjuvant or preoperative chemotherapy also plays a role in ACC treatment. Jeffrey E. Lee, MD, professor and chair of the Department of Surgical Oncology at MD Anderson Cancer Center, discussed the use of neoadjuvant therapy during the October symposium and shared his work with Endocrine News.
“Although treatments have varied, most patients have received combinations of mitotane together with etoposide, doxorubicin, and cisplatin chemotherapy,” Lee explains. “The rationale for this combination is supported by the results of the FIRM-ACT trial, which established this regimen as a standard of care for patients with advanced adrenocortical carcinoma.” The results of FIRM-ACT (The First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment) were published in a June 2012 issue of The New England Journal of Medicine.
Lee says selected patients with ACC have been treated with this regimen at his institution since 1995.
“Since the neoadjuvant approach has not yet been tested in a randomized, prospective trial, it is not possible to be certain that outcomes of surgery are improved,” he says. “However, we do see significant tumor reductions at least as frequently as observed in the FIRM-ACT trial. Also, dramatic tumor responses in the vena cava appear to be particularly common, and this can make surgery both more straightforward and more successful.”
Lee adds that the immediate measures of surgical success, for example the rates of complete resection, are very high. Also, for patients receiving this neoadjuvant therapy, rates of being disease-free for the long term and their overall survival appear to be at least as good as patients with earlier-stage ACC treated in the standard way of surgery first.
“Currently we are only treating patients with borderline resectable ACC in this way,” Lee explains. “This is because the approach cannot yet be considered standard, and our experience with it is still relatively limited.”
“While ultimately a neoadjuvant or preoperative approach like this could also be of benefit to ACC patients with resectable, early-stage disease, we believe the best next step is to apply the treatment to a larger group of borderline resectable patients in a multi-institutional phase II trial to evaluate response rates, surgical success, and patient outcomes.”
Collaborating for Better Outcomes
Finding large groups of patients for such multi-institutional trials is another goal of the collaborations that took place at the symposium. Collaboration helps to understand the biology of the disease, to understand the genetics of the disease, and to cooperate with each other and perhaps even with pharmacologic companies to engage in substantive clinical trials, according to Hammer.
“Clinical trials are partly limited by the patient population that you can get engaged in a trial,” he explains. “And for a rare disease where most doctors in the United States have never seen a case, or if they do, have only seen one case in their career, it becomes essential to collaborate for the science and delivery of care.”
“What we’ve learned about adrenal cancer — with this now 5th international symposium — is that we have made our strides through such international engagement,” Hammer says. “[And] we’ve been able to leverage our relationships with each other in the academic world to engage both the government, in terms of funding and research studies, and the pharmacologic industry, for the support of large trials with new drugs that have been developed, [has been done] in part, in association with academic colleagues,” Hammer says.
Hammer adds that a highlight of the symposium presentations was that the adrenal cancer community has learned from a few large genomic studies that there are only a handful of mutations, which are clearly important for either the formation of adrenal cancer or its progression.
“We hope these will be drivers for the cancer, that the cancers are addicted to these genetic mutations,” he says. “It’s those genes that may be the targets of new therapy. And that’s exciting.”
“We should all be calling our congresswomen and men to try get more [basic science and academic research] funding. It’s been terrible what we’ve seen the in last couple of years in terms of some of the decisions that have been made about cutting funding. But having said that, the basic research that is done in academia is really the foundation of how then, ultimately, the industry can leverage that work to try to make it into drugs for patients.” — Carol Gallagher, PharmD, biopharmaceutical expert/partner, New Enterprise Associates
The Power of Patient Advocates
Although the numbers of patients with adrenal cancer may be small, patients around the world are finding their voice and becoming advocates for their care. The symposium hosted parallel sessions for patients, which gave them an important opportunity to engage with the medical community as well as with other patients and families.
“In the world of healthcare, patients are increasingly and appropriately taking their advocacy and their care into their own hands,” Hammer says. “With the power of the internet, partly, people are appropriately more empowered to educate themselves, and indeed to push research in appropriate directions through their own funding mechanisms and advocacy campaigns.”
Biopharmaceutical expert Carol Gallagher, PharmD, delivered the symposium’s keynote address, where she echoed this sentiment.
“Across cancers in general, we just need to have a continued effort but even more so in the rare cancers where the number of voices of patients may not be as many,” she says. “With adrenal cancer you may not have interacted with someone in your family, so getting the word out that we still have a long way to go in terms of helping these patients is important.”
“We should be really worried about the funding of basic science and academic research,” Gallagher added. “We should all be calling our congresswomen and men to try get more funding. It’s been terrible what we’ve seen the in last couple of years in terms of some of the decisions that have been made about cutting funding. But having said that, the basic research that is done in academia is really the foundation of how then, ultimately, the industry can leverage that work to try to make it into drugs for patients.”
— Fauntleroy is a freelance writer based in Carmel, Ind., and a regular contributor to Endocrine News. She wrote about using dogs to sniff out thyroid cancer in the January issue.