Metoclopramide,Dexamethasone, or Palonosetron for Prevention of Delayed Chemotherapy‐Induced Nausea and Vomiting After Moderately Emetogenic Chemotherapy (MEDEA): A Randomized,Phase III,Noninferiority Trial

BackgroundFor the prevention of chemotherapy‐induced nausea and vomiting (CINV) during the delayed phase (24–120 hours) after moderately emetogenic chemotherapy (MEC), the use of 3‐day dexamethasone (DEX) is often recommended. This study compared the efficacy and safety of two DEX‐sparing regimens with 3‐day DEX, focusing on delayed nausea.Patients and MethodsThis open‐label, randomized, phase III study was designed to demonstrate noninferiority of two DEX‐sparing regimens: ondansetron + DEX on day 1 + metoclopramide on days 2–3 (MCP arm), and palonosetron + DEX on day 1 (PAL arm) versus ondansetron on day 1 + DEX on days 1–3 (DEX arm) in chemotherapy‐naïve patients receiving MEC. Primary efficacy endpoint was total control (TC; no emetic episodes, no use of rescue medication, no nausea) in the delayed phase. Noninferiority was defined as a lower 95% CI greater than the noninferiority margin set at −20%. Secondary endpoints included no vomiting, no rescue medication, no (significant) nausea, impact of CINV on quality of life, and antiemetics‐associated side effects.ResultsTreatment arms were comparable for 189 patients analyzed: predominantly male (55.7%), median age 65.0 years, colorectal cancer (85.7%), and oxaliplatin‐based chemotherapy (81.5%). MCP demonstrated noninferiority to DEX for delayed TC (MCP 56.1% vs. DEX 50.0%; 95% CI, −11.3%, 23.5%). PAL also demonstrated noninferiority to DEX (PAL 55.6% vs. DEX 50.0%; 95% CI, −12.0%, 23.2%). There were no statistically significant differences for all secondary endpoints between treatment arms.ConclusionThis study showed that DEX‐sparing regimens are noninferior to multiple‐day DEX in terms of delayed TC rate in patients undergoing MEC. ClinicalTrials.gov identifier. {"type":"clinical-trial","attrs":{"text":"NCT02135510","term_id":"NCT02135510"}}NCT02135510.Implications for PracticeChemotherapy‐induced nausea and vomiting (CINV) in the delayed phase (24–120 hours after chemotherapy) remains one of the most troublesome adverse effects associated with cancer treatment. In particular, delayed nausea is often poorly controlled. The role of dexamethasone (DEX) in the prevention of delayed nausea after moderately emetogenic chemotherapy (MEC) is controversial. This study is the first to include nausea assessment as a part of the primary study outcome to better gauge the effectiveness of CINV control and patients’ experience. Results show that a DEX‐sparing strategy does not result in any significant loss of overall antiemetic control: DEX‐sparing strategies incorporating palonosetron or multiple‐day metoclopramide are safe and at least as effective as standard treatment with a 3‐day DEX regimen with ondansetron in controlling delayed CINV—and nausea in particular—following MEC.     

Oral Ondansetron 8 mg Twice Daily is as Effective as 8 mg Three Times Daily in the Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Cancer Chemotherapy

The efficacy and safety of ondansetron 8 mg BID compared with 8 mg TID for 3 days in the prevention of nausea and vomiting in 402 patients on cyclophosphamide (≧500 mg/m²)-based chemotherapy were evaluated in a multicenter, randomized, double-blind, stratified study. The percentage of patients with no emetic episodes over the 3-day study period was 61% in the ondansetron BID group compared with 58% in the ondansetron TID group. Among patients with at least one emetic episode, the mean time to emesis was 14 hr and 17 min in the ondansetron BID group compared with 12 hr and 48 min in the ondansetron TID group. Patients' daily appetite ratings and nausea scores were not significantly different between groups. Clinical laboratory and adverse event profiles were similar between groups. This study is the first large-scale, double-blind trial to demonstrate that ondansetron 8 mg BID for 3 days, a dosing regimen that may enhance patient convenience and compliance, is as effective as ondansetron 8 mg TID for 3 days in the prevention of nausea and vomiting associated with cyclophosphamide-based chemotherapy.     

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial

BackgroundOlanzapine is an inexpensive and durable agent for the treatment of chemotherapy‐induced nausea and vomiting and is also superior to neurokinin‐1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)‐induced nausea and vomiting in patients with thoracic malignancies.Materials and MethodsWe conducted a prospective, open‐label, single‐arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0–120 hours).ResultsBetween February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0–120 hours), acute (0–24 hours), and delayed phases (24–120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed.ConclusionProphylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three‐drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA‐based regimen. Clinical trial identification number: UMIN000031267.Implications for PracticeThe results of this phase II trial indicated that the prophylactic administration of low‐dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high‐dose carboplatin chemotherapy.     

Phase III Randomized Trial of Palonosetron and Dexamethasone With or Without Aprepitant to Prevent Nausea and Vomiting Induced by Full-dose Single-day Cisplatin-based Chemotherapy in Lung Cancer

Introduction

This study aimed to determine the efficacy and safety of aprepitant, palonosetron, and dexamethasone to prevent chemotherapy-induced nausea and vomiting in patients with locally advanced or metastatic lung cancer receiving full-dose single-day cisplatin-based combination chemotherapy.

S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized,Open-label,Multicenter, Phase III Superiority Trial

BackgroundThe efficacy of S-1 plus oxaliplatin (SOX) as postoperative adjuvant chemotherapy for colon cancer has not been established. This randomized phase III study was designed to verify the superiority of SOX over tegafur-uracil and leucovorin (UFT/LV) in patients with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries).Patients and MethodsPatients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m² of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 cycles) or SOX (100 mg/m² of oxaliplatin on day 1 and 80 mg/m² of S-1 on days 1-14, every 21 days, 8 cycles). The primary endpoint was disease-free survival (DFS).ResultsA total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the primary analysis. The 3-year DFS was 60.6% (95% confidence interval [CI], 56.0%-64.9%) in the UFT/LV group and 62.7% (95% CI, 58.1%-66.9%) in the SOX group. The stratified hazard ratio for DFS was 0.90 (95% CI, 0.74-1.09; stratified log-rank test, P = .2780). In the N2b subgroup, the 3-year DFS was 46.0% (95% CI, 37.5%-54.0%) in the UFT/LV group and 54.7% (95% CI, 45.7%–62.7%) in the SOX group (hazard ratio, 0.76; 95% CI, 0.55-1.05).ConclusionAs postoperative adjuvant chemotherapy, SOX was not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer.     

Prognostic Factors of Survival in a Randomized Phase III Trial (MPACT) of Weekly nab‐Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone in Patients With Metastatic Pancreatic Cancer

Background.

nab-Paclitaxel in combination with gemcitabine has emerged as a new treatment option for patients with metastatic pancreatic cancer (MPC), based on superiority over gemcitabine demonstrated in the phase III MPACT trial. Previously, Karnofsky performance status (KPS) score and the presence of liver metastases were shown to be predictive of survival with nab-paclitaxel plus gemcitabine treatment. This analysis sought to further explore the relationship between clinical characteristics and survival in the MPACT trial and to identify potential predictors of overall survival and progression-free survival in patients with MPC.

Materials and Methods.

Cox regression models adjusted for stratification factors and a stepwise multivariate analysis of prespecified baseline prognostic factors were performed.

Results.

Treatment effect was significantly associated with survival, with a similar magnitude of reduction in risk of death compared with the previously reported primary analysis. Treatment effect consistently favored nab-paclitaxel plus gemcitabine across the majority of the prespecified factors. In addition to KPS score and presence of liver metastases, age and number of metastatic sites were independent prognostic factors of overall and progression-free survival. Baseline carbohydrate antigen 19-9 was not found to be an independent prognostic factor of survival in this analysis.

Conclusion.

The results of this analysis confirm broad utility of nab-paclitaxel plus gemcitabine for the treatment of MPC. In addition, these findings suggest that KPS score, presence of liver metastases, age, and number of metastatic sites are important predictors of survival that may be useful when making treatment decisions and designing future clinical trials.