Many patients with hematologic cancers receiving highly emetic chemotherapy regimens do not achieve adequate control of chemotherapy-induced nausea and vomiting (CINV), according to study results presented at the 2016 ASH Annual Meeting and Exposition.
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The lack of acceptable CINV control may be caused by a variety of factors, including inadequate prophylaxis receipt or physician misunderstanding, said Lee S Schwartzberg, MD, FACP, executive director of West Cancer Center and chief of the division of hematology and oncology at University of Tennessee Health Science Center (Memphis, TN).
“Outcomes are variable due to the small amounts of clinical trials investigating highly emetogenic multi-day chemotherapy regimens, as well as the variability of chemotherapy regimens,” Schwartzberg told Journal of Clinical Pathways. “It is also possible that hematologists have not focused as much on the evidence base associated with CINV prophylaxis as solid tumor oncologists.”
Patients undergoing with high-grade hematologic malignancies and those undergoing pre-conditioning for stem cell transplants (SCTs) frequently receive highly emetic, multi-day chemotherapy. Guidelines recommend that patients receiving such therapies utilize a three-drug prophylaxis comprised of a 5-HT3 receptor antagonist, an NK-1 receptor antagonist, and corticosteroids; however, the utilization of such regimens in blood cancer patients had not been studies.
Schwartzberg and colleagues conducted a prospective observational study to determine rates of prophylaxis receipt and CINV control in this patient population. Their study included data from 76 patients (median age, 58 years; 68% men) undergoing SCT pre-conditioning (n = 72) or receiving a multi-day chemotherapy regimen that included at least one highly emetic drug (n = 4). The most commonly observed diseases in the patient population included non-Hodgkin lymphoma (n = 27), multiple myeloma (n = 19), and acute myeloid leukemia (n = 15).
Patients kept a diary during treatment, and were asked to fill out Functional Living Index-Emesis (FLIE) questionnaires daily. Surveys began at the time of screening and continued for up to 5 days following final chemotherapy treatment. The researchers recorded daily use of scheduled antiemetic and rescue medications.
A total of 71 patients completed all surveys, all of whom received one or more highly emetic therapies on their first day of treatment. The most common chemotherapy regimen among study participants was carmustine, etoposide, cytarabine, and melphalan (n = 28); 18 patients received high-dose melphalan, and eight patients received melphalan, fludarabine, and campath.
Thirty-seven percent (n = 28) received the recommended three-drug prophylaxis combination, and 32% (n = 24) received a 5-HT3 receptor antagonist with dexamethasone. Nine patients (12%) received 5-HT3 receptor antagonists alone and two patients (3%) received 5-HT3 receptor antagonists in combination with metoclopramide. The remaining patients received other combinations (n = 10; 13%) or had no regimens documented (n = 3; 4%).
Twenty percent (n = 15) of patients achieved a complete response, which the researchers defined as no vomiting and no use of rescue medication. Schwartzberg and colleagues observed significant differences in complete response by date, from 95% on day 1 of treatment to 46% by the end of the study period (P = .041). Mean FLIE scores significantly increased from 19.9±3.1 before chemotherapy to 22.4±3.3 overall (P = .0031).
“We need more clinical research, but there are a lot of things that can already be fixed,” Schwartzberg said. “The majority of patients did not receive the recommended three-drug prophylactic regimen at all. This is not guideline-concordant. The scheduling of drugs was also unclear. No patients on study received second-generation NK-1 receptor antagonists or newer 5-HT3 receptor antagonists like palonosetron [Aloxi; Eisai, Helsinn]. It is also possible that patients are not receiving appropriate supportive care, because doctors feel that the patients are receiving so many drugs in their chemotherapy regimens. That is a matter of attitude that can be changed.”—Zachary Bessette