Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

Current Status and Issues of Collaboration Between Physicians and Pharmacists in Fertility Preservation.

Purpose: This study addresses the critical issue of fertility preservation among young patients with cancer in Japan, recognizing the brief decision-making window and the need for comprehensive support. Pharmacists, well-versed in the side effects of anticancer drugs, can play a vital role in this support process. However, the extent of pharmacists' involvement in fertility preservation remains unclear. We aimed to investigate pharmacists' roles in addressing cancer treatment-induced fertility concerns and their collaboration with physicians, offering insights into enhancing pharmacist participation in fertility preservation. Methods: A survey conducted between April and July 2022 targeted doctors and pharmacists at cancer treatment hospitals, along with pharmacists affiliated with the Japanese Society of Pharmaceutical Health Care and Sciences. Results: Our findings indicated that although pharmacists had limited knowledge about gonadotoxicity and fertility, they expressed readiness to conduct research and provide information when consulted. Approximately 10%-20% of the pharmacists participated in explaining the primary disease at diagnosis. Pharmacists played a more prominent role after establishing chemotherapy regimens, with less involvement in its formulation. Notably, treatment decision case conferences emerged as crucial forums for gathering patient data, confirming treatment plans, and identifying those in need for fertility preservation information. Roughly half of the pharmacists attended these conferences, suggesting a need for increased participation. Conclusion: Enhancing physician-pharmacist collaboration could be pivotal for effective fertility preservation. This requires augmenting the knowledge and awareness of both professions and encouraging greater participation in case conferences to create a conducive environment for addressing this critical aspect of cancer care.

Antiemetic Efficacy of Adding Olanzapine 5 mg to Aprepitant, Palonosetron and Dexamethasone-Sparing After Day Two for Cancer Patients Receiving Anthracycline and Cyclophosphamide.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) decrease patient quality of life (QOL). We evaluated the efficacy of adding 5 mg Olz to a three-drug steroid-sparing antiemetic regimen (aprepitant, palonosetron, and dexamethasone-sparing after day two) for breast cancer (BC) patients receiving anthracycline plus cyclophosphamide (AC) chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed the records of 177 BC patients with no previous highly emetogenic chemotherapy history receiving AC plus the steroid-sparing three-drug regimen or the steroid-sparing four-drug regimen including Olz 5mg at our hospital between January 2012 and December 2018. The primary endpoint was complete response (CR), defined as no vomiting and no usage of rescue medication during the first AC cycle. We analyzed the odds ratio (OR) of the CR with 95% confidence interval (CI) in the three-drug group against the four-drug group. The OR was adjusted for types of anticancer drugs by the Cochran-Mantel-Haenszel (CMH) test. Secondary endpoints were incidences of nausea, anorexia, fatigue, and somnolence during the first cycle. RESULTS: Compared to the three-drug group, the four-drug group demonstrated high incidence of no vomiting (71% vs 95%), a similar incidence of no rescue medication usage (50% vs 51%), and a similar CR rate (45% vs 49%). The OR of the CR rate in the three-drug group against the four-drug group after CMH adjustment for drug type was 0.958 (95% CI, 0.46-1.98). Compared to the three-drug group, the four-drug group demonstrated identical incidence of nausea (66%), but lower incidences of anorexia (78% vs 35%) and fatigue (86% vs 73%). The incidence of somnolence in the four-drug group was 49%. We did not have data of somnolence for the three-drug group in the records. CONCLUSION: Adding 5 mg Olz to the steroid-sparing three-drug combination can reduce vomiting, anorexia, and fatigue, although there was no difference in CR rate.

Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1-4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy.

INTRODUCTION: Dexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although our multicentre randomised double-blind comparative study verified non-inferiority of sparing DEX after day 2 of chemotherapy when combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) for patients receiving HEC regimen, DEX sparing was not non-inferior in patients receiving cisplatin (CDDP)-based HEC regimens in subgroup analysis. Recently, the efficacy of the addition of olanzapine (OLZ) to standard triple antiemetic therapy on HEC has been demonstrated by several phase III trials. This study aims to confirm non-inferiority of DEX sparing when it is combined with NK-1RA, Palo and OLZ in patients receiving CDDP-based HEC regimens. METHODS AND ANALYSIS: This is a randomised, double-blind, phase III trial. Patients who are scheduled to receive CDDP ≥50 mg/m2 as initial chemotherapy are eligible. Patients are randomly assigned to receive either DEX on days 1-4 or DEX on day 1 combined with NK1-RA, Palo and OLZ (5 mg). The primary endpoint is complete response (CR) rate, defined as no emesis and no rescue medications during the delayed phase (24-120 hours post-CDDP administration). The non-inferiority margin is set at -15.0%. We assume that CR rates would be 75% in both arms. Two hundred and sixty-two patients are required for at least 80% power to confirm non-inferiority at a one-sided significance level of 2.5%. After considering the possibility of attrition, we set our final required sample size of 280. ETHICS AND DISSEMINATION: The institutional review board approved the study protocol at each of the participating centres. The trial result will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000032269.

Placebo-Controlled, Double-Blinded Phase III Study Comparing Dexamethasone on Day 1 With Dexamethasone on Days 1 to 3 With Combined Neurokinin-1 Receptor Antagonist and Palonosetron in High-Emetogenic Chemotherapy.

Purpose We evaluated the noninferiority of dexamethasone (DEX) on day 1, with sparing on days 2 and 3, combined with neurokinin-1 receptor antagonist (NK1-RA) and palonosetron (Palo) compared with the 3-day use of DEX in highly-emetogenic chemotherapy (HEC). Patients and Methods Patients who were scheduled to receive HEC (cisplatin ≥ 50 mg/m2 or anthracycline plus cyclophosphamide) were randomly assigned to receive either DEX on days 1 to 3 (Arm D3) or DEX on day 1 and placebo on days 2 and 3 (Arm D1) combined with NK1-RA and Palo. The primary end point was complete response (CR), defined as no emesis and no rescue medications during the overall (0 to 120 h) phase. The noninferiority margin was set at -15.0% (Arm D1 - Arm D3). Results A total of 396 patients-196 and 200 patients in Arms D3 and D1, respectively-were evaluated. CR rates during the overall period were 46.9% for Arm D3 and 44.0% for Arm D1 (95% CI, -12.6% to 6.8%; P = .007). CR rates during the acute (0 to 24 h) phase were 63.3% and 64.5% for Arms D3 and D1, respectively (95% CI, -8.1% to 10.6%; P < .001), and they were 56.6% and 51.5%, respectively, during the delayed (24 to 120 h) phase (95% CI, -14.8% to 4.6%; P = .023). Hot flushes and tremors were observed more frequently as DEX-related adverse events on days 4 and 5 in Arm D3, whereas anorexia, depression, and fatigue were observed more frequently on days 2 and 3 in Arm D1. As an indication of quality of life, global health status was similar in both arms. Conclusion Antiemetic DEX administration on days 2 and 3 can be spared when combined with NK1-RA and Palo in HEC.