Chemotherapy-Induced Nausea and Vomiting (CINV) in Hematologic Malignancy Patients Receiving Multi-Day Highly Emetogenic Chemotherapy (HEC)

INTRODUCTION

Despite recent advances in CINV prophylaxis, many questions remain unanswered including optimal treatment for hematologic malignancy (HM) patients receiving multi-day chemotherapy regimens. As preparation for stem cell transplant (SCT) and for high grade HM, highly emetogenic chemotherapy (HEC) containing regimens are often utilized. International guidelines recommend a three-drug combination of a 5-HT₃receptor antagonist (5-HT3 RA), an NK-1 receptor antagonist (NK-1 RA) and dexamethasone (dex) before HEC. Little is known about CINV prevention in HM multi-day regimens.

METHODS

We conducted a prospective observational study in U.S. research centers with expertise in HM and SCT surveying providers and adult patients receiving up to 7 consecutive days of chemotherapy including at least one HEC drug. Those receiving concurrent radiation therapy were excluded as were patients taking antiemetics or having nausea and vomiting prior to initiation of chemotherapy. Patients completed a diary and a modified Functional Living Index - Emesis (FLIE) questionnaire daily, beginning at screening, during chemotherapy, and for up to 5 days after the last day of treatment. Daily use of scheduled antiemetics and rescue medication was collected. The primary objective was to survey patterns of CINV care for multi-day chemotherapy in HM and assess efficacy of the intervention.

RESULTS

Seventy-six patients were enrolled at 5 centers (range 8 -25 patients per center) between May 2015 and February 2016. Of the patients, 72 underwent pre-SCT conditioning and 4 multi-day chemotherapy for HM. Forty-nine (68%) were male and 58 (81%) were Caucasian; median age was 58 (range 22-74). The most common diagnoses were NHL, 27 (36%); multiple myeloma, 19 (25%); and AML, 15 (20%). Seventy-one patients completed all surveys. All received ≥ 1 HEC drug on day 1. The most common chemotherapy regimens were BEAM, 28 (37%), high-dose melphalan, 18 (26%), melphalan, fludarabine, and campath, 8 (11%) and fludarabine and cyclophosphamide, 4 (5%). Anti-emetic therapy was highly variable, both prior to day 1 chemotherapy and throughout multi-day treatment. On day 1 the most common regimens included: a combination of 5-HT3 RA, NK-1 RA, dex in 28 (37%); 5-HT3 RA + dex in 24 (32%); 5-HT3 RA alone in 9 (12%); 5-HT3 RA and metoclopramide in 2 (3%); other 10 (13%) and none documented 3 (4%). Complete response rate (defined as no vomiting and no use of rescue medications) was observed in 15 patients (20%); complete response by day ranged from 95% on day 1 to 46% on end of study day (p=0.041). Mean±SD nausea scores by FLIE increased from 19.9±3.1 pretreatment to 22.4±3.3 overall (p=0.0031).

CONCLUSION

Approaches to CINV in SCT and HM patients receiving multi-day HEC regimens are highly variable. A large majority of patients receiving multi-day chemotherapy are not achieving adequate control of nausea or vomiting. Additional clinical trials and development of evidence-based approaches to CINV prophylaxis in HM patients throughout multi-day chemotherapy are critical to improve supportive care.