Breast most cancers (BC) is essentially the most continuously recognized most cancers amongst ladies and the main reason behind cancer-related dying amongst ladies globally.1 Anthracycline mixed with cyclophosphamide (AC) is the usual routine for early and superior BC.2–4 Chemotherapy-induced nausea and vomiting (CINV) decreases high quality of life (QOL) and might negatively affect BC remedy consequence.5 AC is classed as a extremely emetogenic chemotherapy (HEC) by a number of worldwide tips.6–8 The beneficial antiemetic remedy for CINV in sufferers receiving AC is a three- or four-drug mixture of the neurokinin-1 receptor antagonist (NK1-RA), the serotonin 5-HT3 receptor antagonist (5-HT3-RA), and dexamethasone (Dex) with or without olanzapine (Olz).6–8
Olz is an antipsychotic that acts on a number of receptors, together with dopamine receptors (D1, D2, and D3), serotonin receptors (5-HT2A, 5-HT2C, and 5-HT3), alpha1 adrenergic receptors, muscarinic cholinergic receptors, and histamine sort 1 receptors (H1).9,10 Antagonism of D2, 5-HT2C, and 5-HT3 receptors particularly could contribute to the antiemetic impact of Olz. Due to this fact, Olz has been the topic of a number of scientific trials investigating its efficacy as an antiemetic drug. A latest Section III trial reported that Olz (10 mg) in a four-drug mixture was superior to a normal three-drug mixture for suppression of nausea and vomiting induced by HEC.11 In that examine, nonetheless, the dose of Olz was 10 mg and sufferers receiving Olz skilled considerably extra extreme sedation on day two in comparison with these receiving placebo. One other latest Section II dose-finding examine reported that for sufferers receiving cisplatin, full response (CR; no emesis and no use of rescue drugs) within the delayed section (24–120 h after the beginning of cisplatin remedy) was achieved in 78% (80% CI: 70.3–83.8, P = 0.01) of the ten mg Olz arm and 86% (80% CI: 79.2–90.7, P < 0.001) of the 5 mg Olz arm (P worth for H0: full response charge ≤ 65%). As well as, the Olz 5 mg arm confirmed a decrease incidence of somnolence than the ten mg arm. Additional, the four-regimen together with 5 mg Olz was extra tolerable, particularly in sufferers of Japanese ethnicity.12 Because of these research, Olz 5 mg was accepted as an antiemetic drug by the Ministry of Well being, Labour and Welfare of Japan with public data based-application in December 2017.
A latest section III trial additionally discovered that antiemetic Dex administration on days two and three might be spared when mixed with NK1-RA and palonosetron in HEC (the DEX-1 examine).13 Dex has a number of adversarial results, corresponding to insomnia, indigestion/epigastric discomfort, agitation, elevated urge for food, weight achieve, and diminished bone density.14,15 Furthermore, dose-dense epirubicin and cyclophosphamide, one of many AC regimens used to deal with early-stage BC, will increase the danger of pneumocystis pneumonia (PCP),16 and PCP is considered related to steroid use.17 Steroid-sparing could subsequently be helpful for reducing Dex-induced adversarial occasions (AEs) in scientific apply. Nevertheless, the therapeutic advantages of including Olz (5 mg) to a normal three-drug steroid-sparing routine (aprepitant, palonosetron, and Dex-sparing after day two) has not been established for AC-induced nausea and vomiting.
We hypothesized that the antiemetic efficacy of including Olz 5mg to the usual three-drug mixture can be superior to the usual three-drug mixture in Japanese BC sufferers receiving AC.
Sufferers and Strategies
This examine was carried out in accordance with Declaration of Helsinki, and the institutional evaluate board of St. Marianna College Faculty of Drugs accepted the current examine (approval quantity 4881). The aims and strategies of the examine in addition to the dealing with of private data had been supplied on the web site of our hospital. The sufferers had been defined that they might freely withdraw from the examine at any time upon contacting us concerning the identical. The ethics committee of St. Marianna College Faculty of Drugs Hospital permitted to carry out retrospective examine with out consent statements (opt-out technique).
The eligibility standards for this examine had been as follows: age ≥20 years and receiving the primary cycle of AC remedy, Japanese Cooperative Oncology Group efficiency standing (ECOG-PS) 0–2, absolute neutrophil rely ≥1500 cells/mm3, aspartate aminotransferase and alanine aminotransferase ≤100 IU/L, blood bilirubin ≤2.0 mg/dL, and creatinine ≤1.5 mg/dL. We extracted the next baseline scientific data for evaluation: age on the time of remedy, intercourse, physique floor space (BSA), physique mass index (BMI), inpatient or outpatient remedy setting, ECOG-PS, most cancers stage, sort of AC routine and dose, antiemetic use, CINV signs, use of rescue medicine, and bone marrow, liver, and kidney operate.
Exclusion standards had been as follows: nausea or vomiting earlier than the primary AC cycle, use of different medication which will forestall CINV corresponding to antipsychotics, antidepressants, corticosteroids, or dopamine receptor antagonists, comorbidities that induced nausea and/or vomiting previous to the initiation of chemotherapy (symptomatic gastrointestinal illness, accumulation of ascitic fluid or pleural effusion, and mind metastases), administration of non-standard antiemetic remedy, being pregnant, uncontrolled diabetes mellitus (DM) through the examine interval (the usage of Olz is contraindicated for sufferers with previous or present DM historical past or HbA1c ≥ 6.5%), and data missing AE knowledge. Sufferers had been excluded from knowledge evaluation if BC was recurrent, in stage IV. We thought of that the bodily or psychological situation of sufferers with stage IV illness could have an effect on the incidence of AEs.
Steady variables are expressed as median [range] and categorical variables as frequency or proportion.
We reviewed the digital medical data (EMRs) of our hospital between January 2012 and December 2018. Affected person data had been de-identified and analyzed anonymously.
On this examine, the AC routine included epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) tri-weekly (EC), epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) biweekly with pegfilgrastim assist (dose-dense EC), and the FEC routine consisted of epirubicin (100 mg/m2), cyclophosphamide (500 mg/m2), and 5-fluorouracil (500 mg/m2) triweekly.
In January 2018, we switched our commonplace antiemetic administration for BC sufferers receiving the AC routine from a three-drug mixture to a four-drug mixture following approval of Olz as an antiemetic drug by the Ministry of Well being, Labour and Welfare of Japan. Beforehand (the three-drug mixture), oral aprepitant (125 mg) was administered 60 minutes previous to chemotherapy, and intravenous palonosetron (0.75 mg) and Dex (12 mg for EC and FEC, 10 mg for dose-dense EC) had been administered quarter-hour previous to chemotherapy for sufferers on day one, adopted by oral aprepitant (80 mg) on day two and three. At current (the four-drug mixture), all sufferers obtain oral Olz (5 mg) earlier than dinner on days one to 4 as a fourth drug (the accepted utilization of Olz in Japan). For rescue medicine, oral prochlorperazine (5 mg) and alprazolam (0.4 mg) had been prescribed for all sufferers.
Throughout chemotherapy, main AEs together with CINV signs had been assessed and recorded routinely in medical charts by pharmacists and nurses on the chemotherapy middle moderately than by physicians on the outpatient clinic. On the day one of many second cycle, the pharmacists interviewed and recorded their AEs through the first cycle within the EMRs. We carried out this examine primarily based on the information within the EMRs. Compliance of oral drugs was checked by hospital pharmacists.
The first endpoint of this examine was CR charge to CINV administration through the first cycle (21 days for EC and FEC, and 14 days for dd EC), the place CR was outlined as no vomiting and no utilization of rescue medicine for CINV. We analyzed CR charges in accordance with age, BMI, and the kind of chemotherapeutic routine. Dose-dense EC is often administered for comparatively youthful sufferers, and youthful age is a danger issue for CINV. Due to this fact, we additionally analyzed CR charge by age and the kind of chemotherapeutic routine.
The secondary endpoints of this examine had been the incidences of nausea, anorexia, and fatigue through the first cycle. The incidence of somnolence was additionally evaluated within the four-drug group. All AEs had been assessed in accordance with the Widespread Terminology Standards for Opposed Occasions (CTCAE), model 4.0.
Initially, we deliberate to check the CR charge between the three-drug group and the four-drug group by propensity rating matching the place “age”, “BSA”, “stage”, and “varieties of anticancer medication” had been included as matching covariates primarily based on scientific findings. After we assessed the group distinction in these covariates, nonetheless, solely “varieties of anticancer drug” differed. Due to this fact, we used stratified evaluation as an alternative of the propensity rating technique. The group distinction in CR through the first cycle is expressed as the chances ratio (OR) with 95% confidence interval (CI). The percentages ratio was adjusted for varieties of anticancer medication by the Cochran–Mantel–Haenszel (CMH) check. AEs are expressed as proportion of sufferers. A P < 0.05 (two-tailed) is taken into account statistically vital for all assessments. All statistical analyses had been carried out utilizing R model 3.5 (https://cran.r-project.org).
Affected person Traits
Determine 1 presents the affected person recruitment and follow-up stream diagram of this examine. From January 2012 to December 2018, a complete of 206 doubtlessly eligible sufferers had been recognized. Twenty-five sufferers had been excluded and extra 4 sufferers had been withdrawn from the evaluation. Lastly, a complete of 177 sufferers had been analyzed on this examine.
Determine 1 Affected person recruitment and follow-up stream diagram.
Affected person traits are summarized in Desk 1. There was no distinction in median age between the three-drug and four-drug group (50 years [27–73 years] vs 49 years [27–74]). All sufferers had been handled as outpatients. The proportion receiving the FEC routine was decrease within the four-drug group (50.5% vs 7.3%), whereas the proportion receiving the dose-dense EC routine was decrease within the three-drug group (0% vs 39%). Alternatively, use of the EC routine didn’t differ between the 2 teams (49.5% vs 53.7%).
Desk 1 Affected person Traits
The CR charge for the primary cycle didn’t differ between the three-drug and four-drug teams (45.3% vs 48.8%; CMH-adjusted OR= 0.958, 95% CI: 0.46 to 1.98, p > 0.99). The incidence of no vomiting was larger within the four-drug group (70.5% vs 95.1%) whereas the incidence of no rescue drugs didn’t differ (49.5% vs 50.5%). We additionally analyzed CR charges in accordance with age, BMI, and the kind of chemotherapeutic routine (Desk 2). Amongst sufferers >60 years of age, CR charge was barely larger within the four-drug group (60.9% vs 65.0%), however didn’t differ between teams amongst sufferers youthful than 60 years. Nevertheless, the CR charge of sufferers receiving dose-dense EC, which was not included within the three-drug group, was markedly decrease than that of EC. Nonetheless, the CR charge was nonetheless larger within the four-drug group when evaluating solely sufferers receiving the EC routine (46.8% vs 56.8%).
Desk 2 Full Response Charge In accordance with Age, Sort of Routine, and Physique Mass Index
The incidences of all grades of nausea, anorexia, fatigue, and somnolence are proven in Desk 3. There was no distinction in nausea incidence between three- and four-drug teams (66.3% vs 65.9%). However, anorexia was much less frequent within the four-drug group (77.9% vs 35.4%). The incidence of fatigue was larger within the three-drug group (86.3% vs.73.2%). The incidence of somnolence was 48.8% within the four-drug group and one of many excluded sufferers discontinued Olz as a consequence of grade 2 somnolence. Knowledge on somnolence weren’t included within the EMRs for the three-drug group. Aside from somnolence, there have been no grade 3 or larger AEs in both group.
Desk 3 Incidences of the Opposed Occasions
On this retrospective observational examine, we verify the antiemetic efficacy of the steroid-sparing four-drug mixture consisting of Olz 5 mg, aprepitant, palonosetron, and Dex (sparing after day two) in Japanese BC sufferers receiving AC. Whereas the CR charge was not superior to the traditional three-drug routine, the no vomiting charge was markedly larger and anorexia charge decrease within the four-drug group, suggesting decreased steroid-induced unintended effects and doubtlessly enhanced QOL.
The CR charge has been used as an indicator of antiemetic efficacy in lots of scientific research.12,13,18–20 A earlier examine by Yeo and colleagues reported a CR (outlined as no vomiting and no use of rescue remedy) charge of 65.0% through the 120 h after beginning the AC routine amongst sufferers receiving the four-drug mixture (10 mg of Olz and Dex sparing after day two).18 The charges of no vomiting and no use of rescue remedy had been larger within the four-drug group than within the three-drug group (68.3% vs 40.0% and 91.7% vs 76.7%, respectively). Furthermore, the speed of no nausea charge (outlined as visible analogue scale < 5mm) was additionally larger within the four-drug group than within the three-drug group (58.3% vs 33.3%).18
However, the incidence of no vomiting was larger within the four-drug group than within the three-drug group, whereas the incidence of no rescue drugs didn’t differ in our examine. The explanation for the dearth of a distinction in rescue drugs utilization is that 5 mg of Olz decreased vomiting however could not have decreased nausea.
There are a number of variations between the examine by Yeo and our examine together with the assessments for nausea, the timing of Olz administration, the dose of Olz, the examine setting and the kind of 5-HT3-RA.
A number of potential scientific trials associated to Olz have used a visible analog scale (VAS) to evaluate nausea, and the definition of “no nausea” in lots of scientific trials can fluctuate (ie, VAS < 5 mm or VAS = 0 mm).11,18,19 However, in our examine, all AEs had been assessed in accordance with the CTCAE, model 4.0. For instance, VAS=5 mm can be grade ≥1 within the CTCAE and wouldn’t end in a dedication of no nausea (since our examine outlined grade 0 as “no nausea”). The variations in evaluation strategies could also be one cause why the distinction in nausea couldn’t be expressed.
Nevertheless, Yeo et al reported that the presence of CTCAE grade 0–1 nausea was additionally larger within the four-drug group than within the three-drug group (98.3% vs 85.0%).18 The variations within the timing of administering Olz could have an effect on the speed of nausea suppression. Olz was administered earlier than chemotherapy in Yeo’s examine and after in our examine. The median time to the primary episode of vomiting after the initiation of chemotherapy was 26.5 h in the usual (APR + Ondansetron + Dex) arm in Yeo’s examine.18 Nausea may need been uncontrolled if Olz was administered after chemotherapy as a result of the time for Olz to achieve its most plasma focus is 4.5 h.21
One other attainable cause for our outcomes is the dose of Olz. The dose of Olz was 10 mg in Yeo’s examine and 5 mg in our examine. Suthinee et al assessed the efficacy of APR or 10 or 5 mg of Olz plus ondansetron and Dex for CINV prophylaxis in sufferers receiving HEC (AC or cisplatin-based routine).19 The speed of no nausea (outlined as a VAS rating of “0”) was 43% of the sufferers receiving 10 mg of Olz, 37% in these receiving 5 mg of Olz and 33% of these within the APR group.19 Within the AC routine, the dose of 10 mg of Olz could also be wanted for the management of nausea.
In our examine, the distribution of remedy regimens differed between the 2 teams, with the proportion receiving FEC markedly larger within the three-drug group and dose-dense EC unique to the four-drug group. The impact of the precise anticancer medication might not be adjusted utilizing “chemotherapeutic routine” because the covariate in stratified evaluation, so we used “varieties of anticancer medication” as an alternative because the covariate in stratified evaluation.
Primarily based on the outcomes of the NSABP B-36 trial, FEC has been excluded as an possibility for adjuvant remedy,1 and has not been used as a perioperative remedy in recent times. Due to this fact, we couldn’t examine the CR charge between the three-drug and four-drug group sufferers receiving FEC. We additionally couldn’t examine the CR charge of sufferers receiving dose-dense EC between teams, though the CR charge was markedly decrease amongst four-drug group sufferers receiving dose-dense EC in comparison with these receiving EC. The sufferers handled with dose-dense EC had been administrated Dex 10 mg on day 1 because of the danger of PCP. In accordance with a meta-analysis by Lemos Duarte and colleagues, dose-dense remedy can enhance the disease-free survival of early BC sufferers with little affect on security,22 and use of dose-dense EC by our hospital started in 2018. Within the GIM2 examine, incidence of grade 1/2 vomiting was numerically larger within the dose-dense EC group than EC or FEC teams.23 A decrease preliminary Dex dose and extra frequent utilization of rescue medicine for vomiting, even for low-grade vomiting, could account for the equal CR charges between teams in our examine. Future research analyzing the impact of including Olz for sufferers receiving dose-dense EC are warranted.
One of the frequent AEs of Olz is somnolence, however a rise in somnolence couldn’t be assessed as there have been no knowledge for the three-drug group.
A retrospective examine reported the antiemetic efficacy and security of a non-steroid-sparing four-drug mixture (5 mg of Olz and Dex from days 1 to 4).20 The incidence of all grades of somnolence within the four-drug group in our examine was larger than that in a earlier examine (Grade 1: 34.3% vs 22%, Grade 2: 12.9% vs 0%).20 Additionally, in a examine of Dex for prophylaxis towards delayed emesis, most cancers sufferers reported reasonable to extreme insomnia (45%);14 subsequently, steroid-sparing may additionally improve somnolence. In our examine, just one affected person self-interrupted as a consequence of grade 2 somnolence, whereas typically Olz was effectively tolerated.
Our examine has the next limitations. 1) It is a single-center, retrospective observational examine so applicability to the broader BC inhabitants is unsure. Typically, the evaluation interval of the examine endpoint in most CINV trials is 120 h or 168 h after the beginning of chemotherapy. Nevertheless, we set the examine interval to be through the first cycle. This retrospective examine was primarily based on knowledge obtained in day by day scientific apply, and the time of look of nausea was not clearly said in all sufferers. The issue on this examine interval is that there’s a chance of accumulating nausea and vomiting corresponding to anxiety-related nausea. In addition to, we didn’t embrace nausea as part of the first endpoint, and we additionally couldn’t assess the sufferers’ QOL. 2) We couldn’t assess different attainable danger elements for CINV, corresponding to alcohol habits, as many such elements weren’t accessible within the data. 3) The AC routine and Dex dose differed between the 2 teams, which might have an effect on antiemetic remedy consequence. 4) The distinction in accepted palonosetron dose between Japan (0.75 mg) and different international locations (0.25 mg) additionally limits applicability to different populations. In Japan, Saito et al carried out a section III examine evaluating palonosetron 0.75 mg and granisetron 0.04 mg/kg for HEC.24 Primarily based on the outcomes of that examine, 0.75 mg is the accepted palonosetron dose in Japan moderately than 0.25 mg beneficial in worldwide tips.6–8 5) We couldn’t consider AEs apart from fatigue and somnolence, corresponding to hyperglycemia or PCP.
Each Olz and corticosteroids have hyperglycemic AEs, so steroid-sparing might scale back the danger of hyperglycemia. Nevertheless, when used as a neoadjuvant or adjuvant remedy, the AC routine is often administrated for 4 cycles, so hyperglycemia might not be an issue as many BC sufferers are comparatively younger and haven’t any comorbidity.
In distinction, PCP is a severe AE, particularly in response to dose-dense remedy, and corticosteroids are thought to extend PCP danger.16,17 In a earlier report, sufferers who developed PCP acquired a median corticosteroid dose of 16.4 mg/day prednisolone (PSL) equivalents [14.3–27.3 mg/day],17 whereas in our steroid-sparing routine, Dex is decreased from 12.4 to 4.8 mg PSL equal/day. A discount in PCP danger through the dose-dense EC routine would supply additional assist for the scientific utility of the Dex-sparing four-drug antiemetic remedy.
Though there was no statistically vital distinction in CR charge between the three-drug and four-drug antiemetic remedy teams, including 5 mg Olz to the usual three-drug mixture with steroid-sparing (Dex on day one solely) decreased the incidence of vomiting, anorexia, and fatigue amongst BC sufferers.
The authors want to thank Enago for the English language evaluate.
M.S. experiences grants from Shionogi, through the conduct of the examine. Y.Ok. experiences private charges from Chugai pharmaceutical, private charges from Eisai, Novartis pharma, Taiho pharma, Daiichi Sankyo, Pfizer, Eli Lilly, AstraZeneca, and Kyowa-Kirin, outdoors the submitted work. Ok.T. experiences grants and private charges from AstraZeneca, Chugai pharmaceutical co. Ltd, Eisai, Taiho pharmaceutical co. Ltd, Takeda pharmaceutical co. Ltd, Nippon Kayaku co. Ltd; grants from MSD Ok.Ok.; private charges from Eli Lilly Japan Ok.Ok., Daiichi Sankyo co. Ltd, and Pfizer, outdoors the submitted work. The authors report no different conflicts of curiosity on this work.
1. Nationwide Complete Most cancers Community (NCCN). Scientific Observe Pointers in Oncology (NCCN Pointers®). Breast Most cancers. Model 1; 2020. Out there from: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
2. Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of Nationwide Surgical Adjuvant Breast and Bowel Venture Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778–785.
3. Peto R, Davies C, et al.; Early Breast Most cancers Trialists’ Collaborative Group (EBCTCG). Comparisons between completely different polychemotherapy regimens for early breast most cancers: meta-analyses of long-term consequence amongst 100,000 ladies in 123 randomised trials. Lancet. 2012;379(9814):432–444.
4. Fossati R, Confalonieri C, Torri V, et al. Cytotoxic and hormonal remedy for metastatic breast most cancers: a scientific evaluate of revealed randomized trials involving 31,510 ladies. J Clin Oncol. 1998;16(10):3439–3460.
5. Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. Delayed nausea and vomiting proceed to cut back sufferers’ high quality of life after extremely and reasonably emetogenic chemotherapy regardless of antiemetic remedy. J Clin Oncol. 2006;24(27):4472–4478.
6. Nationwide Complete Most cancers Community (NCCN) Scientific Observe Pointers in Oncology (NCCN Pointers®). Antiemesis. Model 1. 2019; 2020. Out there from: https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf.
7. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Scientific Oncology Scientific Observe Guideline Replace. J Clin Oncol. 2017;35(28):3240–3261.
8. Multinational Affiliation of Supportive Care in Most cancers. MASCC/ESMO antiemetic guideline 2016 with updates in 2019; 2020. Out there from: https://www.mascc.org/property/Pointers-Instruments/mascc_antiemetic_guidelines_english_v.1.5SEPT29.2019.pdf.
9. Bymaster FP, Calligaro DO, Falcone JF, et al. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996;14(2):87–96.
10. Bymaster FP, et al. Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and α1-adrenergic receptors in vitro. Schizophr Res. 1999;37(1):107–122. doi:10.1016/S0920-9964(98)00146-7
11. Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med. 2016;375(2):134–142. doi:10.1056/NEJMoa1515725
12. Yanai T, Iwasa S, Hashimoto H, et al. A double-blind randomized section II dose-finding examine of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by extremely emetogenic cisplatin-based chemotherapy. Int J Clin Oncol. 2018;23(2):382–388.
13. Ito Y, Tsuda T, Minatogawa H, et al. Placebo-controlled, double-blinded section III examine evaluating dexamethasone on day 1 with dexamethasone on days 1 to three with mixed neurokinin-1 receptor antagonist and palonosetron in excessive emetogenic chemotherapy. J Clin Oncol. 2018;36(10):1000–1006.
14. Vardy J, Chiew KS, Galica J, Pond GR, Tannock IF. Unintended effects related to the usage of dexamethasone for prophylaxis of delayed emesis after reasonably emetogenic chemotherapy. Br J Most cancers. 2006;94(7):1011–1015.
15. Nakamura M, Ishiguro A, Muranaka T, et al. A Potential observational examine on impact of short-term periodic steroid premedication on bone metabolism in gastrointestinal most cancers. Oncologist. 2017;22(5):592–600.
16. Waks AG, Tolaney SM, Galar A, et al. Pneumocystis jiroveci pneumonia (PCP) in sufferers receiving neoadjuvant and adjuvant anthracycline-based chemotherapy for breast most cancers: incidence and danger elements. Breast Most cancers Res Deal with. 2015;154(2):359–367.
17. Yale SH, Limper AH. Pneumocystis carinii pneumonia in sufferers with out acquired immunodeficiency syndrome: related diseases and prior corticosteroid remedy. Mayo Clin Proc. 1996;71(1):5–13.
18. Yeo W, Lai TK, Li L, et al. A randomized examine of olanzapine-containing versus commonplace antiemetic regimens for the prevention of chemotherapy-induced nausea and vomiting in Chinese language breast most cancers sufferers. Breast. 2020;50:30–38.
19. Ithimakin S, Theeratrakul P, Laocharoenkiat A, et al. Randomized, double-blind, placebo-controlled examine of aprepitant versus two dosages of olanzapine with ondansetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in sufferers receiving high-emetogenic chemotherapy. Assist Care Most cancers. 2020;28(11):5335–5342.
20. Kawazoe H, Uozumi R, Murakami A, et al. Olanzapine plus aprepitant, palonosetron, and dexamethasone for nausea and vomiting in sufferers with breast most cancers receiving anthracycline: a retrospective examine. Sci Rep. 2018;8(1):16232.
21. Amamoto T, Irie S, Kumamoto M, et al. Impact of meals on LU170053 (Olanzapine) bioavailability and the bioequivalence of various formulations. Rinshouiyaku. 1998;14(15):2717–2735.
22. Lemos Duarte I, Da Silveira N, Lima JP, et al. Dose-dense chemotherapy versus typical chemotherapy for early breast most cancers: a scientific evaluate with meta-analysis. Breast. 2012;21(3):343–349.
23. Mastro LD, Placido SD, Bruzi P, et al. Fluorouracil and dose-dense chemotherapy in adjuvant remedy of sufferers with early-stage breast most cancers: an open-label, 2 × 2 factorial, randomised Section 3 trial. Lancet. 2015;385(9980):1863–1872.
24. Saito M, Aogi Ok, Sekine I et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting throughout chemotherapy: a double-blind, double-dummy, randomised, comparative section III trial. Lancet Oncol.2009;10(2):115–124.