This was a multicenter, prospective, observational study in which seven institutions throughout Japan participated. We selected National Cancer Center Hospital East, Cancer Institute Hospital, Kyushu Cancer Center, Shikoku Cancer Center, Kindai University Hospital, Kanagawa Cancer Center, and Shizuoka Cancer Center and asked them to participate in this study. All procedures were performed in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the National Cancer Center Institutional Review Board (2012-324) and the Institutional Review Board of each participating hospital.
Enrollment of patients
Written informed consent was obtained from all participants prior to registration. The primary inclusion criteria were ≥20 years of age, diagnosis of solid tumors, no prior chemotherapy, and planned administration of combination therapy with a 5-HT3 receptor antagonist and dexamethasone. The combinations administered were as follows: for lung cancer, carboplatin plus etoposide (CBDCA+ETP), carboplatin plus paclitaxel (CBDCA+PTX), or carboplatin plus pemetrexed therapy (CBDCA+PEM); for breast cancer, cyclophosphamide plus docetaxel therapy (DTX+CPA); for colon cancer: oxaliplatin with fluorouracil and folinic acid chemotherapy (FOLFOX) or capecitabine plus oxaliplatin (CAPOX); and for ovarian cancer, carboplatin plus paclitaxel therapy (CBDCA+ PTX). The exclusion criteria were patients with gastrointestinal obstruction, ascites or pleural effusion, or symptomatic brain metastasis, and those receiving current radiotherapy directed toward the abdomen/pelvis.
Based on the feasibility of each facility, we aimed to register 50 patients per regimen, with 150 colorectal cancer cases, 150 lung cancer cases, 50 ovarian cancer cases, and 40 breast cancer cases per regimen.
Management of patient diaries and collection of required data
Before initiating cancer chemotherapy, patients were provided with 7-day diaries to record their CINV symptoms. They were asked to record digestive symptoms, such as the development and severity of nausea, frequency of vomiting, and number of salvage treatments, including the use of antiemetic medications (e.g., metoclopramide, domperidone, and olanzapine). Nausea was assessed by patients themselves using the 4-point Likert Scale (0: No Nausea, 1: Mild, 2: Moderate, and 3: Severe), and the results were recorded in their daily diaries. Patients were required to write their symptoms in the diary every day for 7 days from the initiation of their anticancer MEC. The investigators and/or their colleagues recorded background patient information, including sex, age, treatment history (history of radiotherapy, use of anticancer drugs, or use of anxiolytic drugs before administration of the anticancer drug), alcohol intake history, smoking history, risk factors for CINV (history of motion sickness or vomiting related to pregnancy), performance status, cancer chemotherapy regimen (type and dose of drug and timing of administration), and details of antiemetic therapy and salvage treatment for CINV extracted from the patients’ diaries. The patients were requested to fill in their diaries and hand them over to the person in charge of this study at the end of the observation period. The diaries were also sent to the secretariat by the investigators after the extraction of the required data.
Patients received a guideline-based combination of a 5HT3RA and dexamethasone for MEC. The dosage of 5HT3RA was either palonosetron in 0.75mg and a first-generation 5HT3RA in standard doses. The dose of dexamethasone was in accordance with each institution’s policy. On day 1 of chemotherapy (acute phase), 5HT3RA and dexamethasone were administered. Day2-3of after chemotherapy (delayed phase), dexamethasone was in accordance with each institution’s policy.
The objective of this study was to evaluate the incidence of CINV for different MEC regimens based on the complete response (CR), total control (TC), and complete control (CC) rates over the entire observation period (0–168 h), acute phase (0–24 h), and delayed phase (24–168 h) of the first cycle of treatment. We also aimed to evaluate the emetic event rate over the entire observation period and time to treatment failure.
The CR rate was defined as the proportion of participants in the analysis set with no emetic events and no antiemetic measures, the TC rate as the proportion of participants with no emetic episodes, no antiemetic measures, and no nausea, and the CC rate as the proportion of participants with no emetic episodes, no antiemetic measures, and less than mild nausea. The severity of nausea was measured using a 4-point Likert Scale. Time to treatment failure was defined as the time to the first emetic episode or use of rescue medications.
Risk factors associated with good control of CINV were assessed for sex, age, motion sickness, drinking habit, smoking history, pregnancy, type of 5HT3RA and CBDCA-chemotherapy, or others associated with CR and TC.
Patient characteristics and CR, TC, and CC rates were summarized using descriptive statistics or contingency tables. Independent risk factors for CR and TC were analyzed using univariate logistic regression. The number of risk factors for CINV in the collected data sets was analyzed by multivariate logistic regression analysis with the backward elimination method. The following independent factors were included in the model: sex, age, motion sickness, drinking habit, smoking history, pregnancy-associated vomiting, and the type of 5HT3RA and CBDCA-based chemotherapy. For all analyses, p-values correspond to two-sided tests, and p < 0.05 was considered to indicate statistical significance. All statistical analyses were performed using SAS 9.2.