Erythropoietin-stimulating agents may be linked to poorer ovarian cancer outcomes

Issue: April 25, 2011

Patients with ovarian cancer receiving erythropoietin-stimulating agents had a mortality rate nearly 15% higher than patients not receiving those agents, according to study results.

Researchers from several sites conducted a multivariate analysis accounting for a variety of demographic and clinical data that included ever use of ESAs in 581 patients. Ever use of these agents was reported by 39% of patients, and never use was reported by 61%.

Recurrence occurred in 80% of patients with ESA experience vs. a recurrence rate of 56% in patients who never used the agents (P<.001). Use of the agents was also linked to a higher mortality rate, 59% vs. 46% (P=.002).

Patients who had experience with ESAs had a PFS of 16 months vs. 24 months among patients not using the drugs, according to Kaplan-Meier analysis results (P<.001). There was no significant difference between the two groups regarding OS (38 vs. 46 months).

Rationale

“Randomized controlled trials have shown that patients who received those agents had poorer survival outcomes,” Rodney P. Rocconi, MD, assistant professor of gynecologic oncology and Abraham A. Mitchell Clinical Cancer Research Scholar at the University of South Alabama Mitchell Cancer Institute, told HemOnc Today. “Critically reviewing that data revealed that critiques of those findings have been relevant.”

Rocconi said ESAs were used as a prophylaxis of, rather than treatment for, chemotherapy-induced anemia, adding that common clinical practice is to use the agents as a treatment for anemia once the hemoglobin has decreased to less than 10 g/dL.

“These results did not mirror common clinical practice,” he said. “Also, these studies were only performed in a few cancer types.”

Rocconi said most clinicians will cease ESA use when the patient becomes asymptomatic or their hemoglobin increases to more than 11 or 12 g/dL.

“What we saw was that many of these studies involved patients being treated until hemoglobin was above 15 or 16 g/dL,” he said. “This is what we called a supratherapeutic dose.”

The current study was an investigation of whether prognosis or survival was worse when the agents were used appropriately, which Rocconi described as treatment for chemotherapy-induced anemia in patients with hemoglobin of less than 10 g/dL, and with lower doses for a shorter period of time.

“Our data support that even when used for the treatment of chemotherapy-induced anemia, these agents conferred a worse survival in ovarian cancer patients,” he said.

Recommendations for use

Rocconi said the agents should be used with caution, noting that peer-reviewed recommendations suggest that when the agents are being used for curative intent, chemotherapy dose delays or reductions should be employed first, as should transfusions.

“There is still a role for erythropoietin-stimulating agents, but that role is for patients on multi-line therapy, patients with recurrence and patients in whom curative intent is not the main goal of treatment,” he said. “Along the current treatment algorithm, I would lean toward chemotherapy dose reduction and dose alteration first, then transfusion, then use of these agents.”

Rocconi said it may be difficult to explore various options in symptomatic patients. “It takes a lot longer for those patients to get rid of their symptoms,” he said. “It is a slower progression of bone marrow recovery.”

When the data were presented, Rocconi said many oncologists had similar concerns with the prior body of research. “It was a question that was left unanswered,” he said. “We have seen a decrease in use of these agents in our practice over the years because of the FDA black box warning. It is a hard sell to convince a patient to take an agent when they have cancer and that agent might lead to progression or worse survival.”

Baseline characteristics were similar between the two groups. Optimal cytoreduction occurred in 67% of patients, and the mean number of chemotherapy regimens administered was 2.4. The median follow-up duration was 27 months.

For more information:

Sullivan P. #27. Presented at: 42nd Annual Meeting of the Society of Gynecologic Oncologists; March 6-9, 2011; Orlando, Fla.

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