Patients’ characteristics

During the period of interest, 113 patients received chemotherapy including CDDP in our orthopedic surgery department, of which 71 patients were included in the analysis, excluding 42 patients who met the exclusion criteria (Fig. 1). All patients were administered neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists, and dexamethasone. Olanzapine was administered prophylactically at a dose of 2.5 mg to 5 mg once daily after dinner or at bedtime for children and the AYA group, and at a dose of 5 mg once daily at bedtime for the MA group. The dosage was determined individually for each patient based on consultation between the physician and pharmacist. The dosage for children was set based on the report by Flank et al., with an initial dose of 0.10 mg/kg/dose as a reference [9]. The main patient characteristics considered when determining the dosage included the presence or absence of concomitant medications with sedative effects, the presence or absence of lower limb dysfunction due to the tumor, and the patient’s body size.

Fig. 1

Patient flowchart and reasons for exclusion. The study included patients with sarcoma younger than 65 years of age treated with cisplatin between January 2011 and March 2020. Exclusion criteria were: (i) prior chemotherapy; (ii) receiving steroids other than inhaled or topical steroids; and (iii) receiving any emetogenic or antiemetic drug within 24 h prior to cisplatin administration, or CTCAE (Common Terminology Criteria for Adverse Events, Version 5.0) Grade 1 or higher nausea and vomiting

The patients’ characteristics are shown in Table 1. Twenty patients (28%) were in the children group, 32 (45%) in the AYA group, and 19 (27%) in the MA group. The proportion of females in each group was 35.0% (7/20) in the children group, 37.5% (12/32) in the AYA group, and 31.6% (6/19) in the MA group. Olanzapine prophylaxis was given to 20.0% (4/20) of the children patients, 25.0% (8/32) of the AYA patients, and 5.3% (1/19) of the MA patients. The proportion of patients who used rescue therapy between CDDP day 1 and day 6 was 80.0% (16/20) in the children group, 65.6% (21/32) in the AYA group, and 52.6% (10/19) in the MA group.

CR rates by time period

The CR rates during the evaluation period were as follows. The overall CR rate was 20% (4/20) in the children group, 28.1% (9/32) in the AYA group, and 42.1% (8/19) in the MA group; the CR rate in the acute phase was 70% (14/20) in the children group, 78.1% (25/32) in the AYA group, and 94.7% (18/19) in the MA group; and the CR rate in the delayed phase was 20% (4/20) in the children group, 28.1% (9/32) in the AYA group, and 42.1% (8/19) in the MA group (Fig. 2). There were no significant differences in CR rates between the overall, acute, and delayed phases in each group (Children, AYA, and MA). The CR rates for each time period from CDDP administration days 1 to 6 are shown in Fig. 3. The respective CR rates for CDDP days 1 through 6 were 70.0% (14/20), 40.0% (8/20), 35.0% (7/20), 50.0% (10/20), 60.0% (12/20), and 65.0% (13/20) in the children group, 78.1% (25/32), 78.1% (25/32), 50.0% (16/32), 37.5% (12/32), 53.1% (17/32), and 56.3% (18/32) in the AYA group, and 94.7% (18/19), 94.7% (18/19), 57.9% (11/19), 57.9% (11/19), 57.9% (11/19), and 63.2% (12/19) in the MA group There were no significant differences in CR rates for each day from CDDP administration days 1 to 6 among the three groups (Children, AYA, and MA).

Fig. 2

Complete response (CR) rate overall and by phase. This bar graph shows the percentage of patients achieving a CR 120 h after initiation of chemotherapy, with CR defined as no vomiting and no need for rescue medication. n.s., not significant

Fig. 3

Complete response (CR) rate by day. This bar graph shows the percentage of patients who achieved a CR on individual days after cisplatin was initiated, with CR defined as no vomiting and no need for rescue medication. n.s., not significant

Non-vomiting rate by time period

The no-vomiting rates during the evaluation period were as follows. The overall control rate was 50% (10/20) in the children group, 59.4% (19/32) in the AYA group, and 78.9% (15/19) in the MA group; the control rate in the acute phase was 95.0% (19/20) in the children group, 96.9% (31/32) in the AYA group, and 100% (19/19) in the MA group; and the control rate in the delayed phase was 50.0% (10/20) in the children group, 59.4% (19/32) in the AYA group, and 78.9% (15/19) in the MA group (Fig. 4). There were no significant differences in no-vomiting rates between the overall, acute, and delayed phases in each group (Children, AYA, and MA). The no-vomiting rates for each time period from CDDP administration days 1 to 6 are shown in Fig. 5. The respective control rates for CDDP days 1 through 6 were 95.0% (19/20), 75.0% (15/20), 85.0% (17/20), 90.0% (18/20), 85.0% (17/20), and 85.0% (17/20) in the children group; 96.9% (31/32), 84.4% (27/32), 78.1% (25/32), 100% (32/32), 93.8% (30/32), and 100% (32/32) in the AYA group; and 100% (19/19), 84.2% (16/19), 100% (19/19), 100% (19/19), 94.7% (18/19), and 100% (19/19) in the MA group. The no-vomiting rate was significantly lower in the AYA group than in the MA group on day 3 (Fisher’s exact probability test p = 0.037). There was no significant difference in no-vomiting rates at other time points.

Fig. 4

No-vomiting rate overall and by phase. This bar graph shows the percentage of patients achieving no-vomiting 120 h after initiation of chemotherapy, with no-vomiting defined as no emesis, regardless of rescue antiemetic use. There were no significant differences in the no-vomiting rates between the overall, acute, and delayed phases in each group. n.s., not significant

Fig. 5

No-vomiting rate by day. This bar graph shows the percentage of patients who achieved no-vomiting on individual days after cisplatin was initiated, with no-vomiting defined as no emesis, regardless of rescue antiemetic use. The no-vomiting rate was significantly lower in the AYA group than in the MA group on day 3 (Fisher’s exact probability test p = 0.037). Statistical significance was defined as p < 0.05 (*); n.s., not significant

The CR rate during the evaluation period for olanzapine-treated patients was 100% in all three groups in the acute phase, and 25% in the children group, 50% in the children and AYA groups and 100% in the MA group overall and in the delayed phase. The CR rates according to olanzapine use were as follows. In the children group, the CR rate was 25.0% (1/4) among olanzapine users and 12.5% (2/16) among non-users. In the AYA group, the CR rate was 50.0% (4/8) among users and 20.8% (5/24) among non-users. In the MA group, the CR rate was 100% (1/1) among the only user and 33.3% (6/18) among non-users.

Percentage of rescue antiemetic use among patients who did not achieve CR

Among patients who did not achieve CR, the number of patients who had vomiting was 10 in the children group, 13 in the AYA group, and 4 in the MA group. Of these, the number of patients who also used rescue antiemetics was 10, 11, and 3, respectively. In this study, the rescue antiemetics administered included antihistamines (H₁ receptor antagonists), phenothiazine antipsychotics (dopamine D₂ receptor antagonists), benzodiazepine anxiolytics, and dopamine D₂ receptor antagonists/prokinetic agents. The choice of agent was made based on the clinical judgment of the attending physician, considering the patient’s symptoms and background.

Percentage of treatment discontinuation among patients who did not achieve CR

In each group, among patients who did not achieve CR, none had a dose reduction of the second course of AP or CDDP therapy. However, treatment discontinuation was observed in 2 of 17 children (11.8%), 5 of 23 AYAs (21.7%), and 8 of 11 MAs (72.7%). The reasons for discontinuation were not related to CINV but included various clinical factors such as renal dysfunction and disease progression, which led to changes in the treatment plan.