According to a recent study by researchers at the School of Medicine, a treatment protocol that trains the immune system to tolerate chemotherapy drugs increases the lifespans of ovarian cancer patients.
Platinum agents, the most effective class of chemotherapy drugs in combating ovarian cancer, induce a severe allergy — or hypersensitivity — in up to 40 percent of patients, according to the study. Since allergic reactions can be life-threatening, healthcare professionals often opt to discontinue the use of these drugs in hypersensitive patients. Alternative chemotherapy treatments, however, are less effective in shrinking tumors.
In a recent Yale study, researchers confirmed that patients with a hypersensitivity to carboplatin — a type of platinum agent — can be systematically desensitized until they no longer experience an allergic reaction to the treatment. The study was published in the Journal of Cancer Research and Clinical Oncology on Sept. 25.
Elena Ratner, a professor at the medical school and co-author of the study, emphasized the importance of maintaining carboplatin chemotherapy as a viable treatment option.
“If we give other chemotherapies, [a patient’s life span] can be as short as nine weeks, so two to three months is all we can expect from other treatments,” she said. “Whereas, with carboplatin treatment, women can live for months and years.”
The team compared the outcomes of two groups of ovarian cancer patients, each of whom had previously received carboplatin treatment. One group contained those without a hypersensitivity to carboplatin, who continued receiving the treatment, while the other included those who had developed a hypersensitivity to carboplatin.
The latter group was administered modified chemotherapy drugs in line with the desensitization protocol. Specifically, these patients received anti-inflammatory drugs in conjunction with small but consecutively increasing doses of carboplatin.
The study found that patients with hypersensitivity who received the desensitization protocol outlived patients without hypersensitivity by an average of four years.
The result was somewhat surprising, said Esther Florsheim, co-author of the study and immunobiologist at the medical school, because it not only provided evidence that desensitization is safe and effective, but also it demonstrated that some combination of the desensitization therapy and the initial hypersensitivity to carboplatin actually improves a patient’s prognosis compared to their nonallergic counterparts.
One potential explanation is that the anti-inflammatory agents administered during desensitization may have tumor-shrinking effects, Florsheim said. Alternatively, allergic sensitivity to carboplatin — associated with abnormally high activity in the immune system — may help downsize the tumors.
Florsheim said she will be conducting further research to tease apart these two hypotheses, using mouse models and human cell cultures to probe underlying biological mechanisms.
In the meantime, Gary Altwerger, primary author of the study and a professor at the medical school, said he hopes that carboplatin desensitization becomes standard practice in the treatment of ovarian cancer, despite a historically controversial reputation.
“One of the things that’s important for us to realize is that carboplatin desensitization protocols are safe and should be part of our algorithm when we’re deciding what chemotherapies to give to patients,” he said. “I can tell you right now that a desensitization protocol isn’t in every oncologist’s mind up front. And I think it’s something that should be.”
Many medical institutions that offer desensitization consider the therapy risky enough to require that patients remain in the Intensive Care Unit while undergoing treatment, Altwerger added.
However, his research suggests that desensitization therapy is reliable and can be administered in an inpatient or outpatient setting. Furthermore, the benefits of continuing carboplatin chemotherapy, rather than switching to an alternative set of chemotherapy drugs, far outweigh any minimal risks.
Altwerger also noted that despite his excitement about the clinical applications of his findings, the study has limitations. Not only is it a retrospective study which made it difficult to ensure balanced participant pools, the findings are only applicable to a small subset of patients — those who initially respond well to carboplatin chemotherapy but later develop a hypersensitivity.
In 2018, about 22,000 people will receive a diagnosis of ovarian cancer in the U.S., according to the American Cancer Society.