A Randomized Cross-over Study of High-dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High-dose Cisplatin

We carried out a randomized, single-blind, cross-over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high-dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty-four patients with primary or metastatic lung cancer, given single-dose cisplatin (> 80 mg/m²) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively ( P =0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively ( P = 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty-four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group ( P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed.     

中剂量灭吐灵,地塞米松联用对DDP化疗时的镇吐作用：94例分析

本文介绍中剂量灭吐灵、地塞米松联用时的镇吐疗效。无呕吐率67％,较文献报道的大剂量地塞米松的无呕吐率56％及大剂量灭吐灵的28％要好。治疗组与对照组相比,各反应梯次,均有非常显著差异。对DDP等强致吐药物,灭吐灵联用时,单次剂量以不少于40mg为宜。     

恩丹西酮和胃复安预防顺铂化疗呕吐反应的疗效分析

采用自身对照方法，观察了１０６例恶性肿瘤病人以顺铂为主联合化疗，于第１，２周期分别使用胃复安，恩丹西酮。预防恶心呕吐反应，有效率分别为：４３．３９％，９２．４５％，二者差异显著。胃复安组８例发生椎体外系反应，恩丹西酮均未出现椎体外系症状。     

Control of Cisplatin-induced Delayed Emesis with Metoclopramide and Dexamethasone: a Randomized Controlled Trial

Forty-two patients with advanced lung cancer undergoing chemotherapycontaining cisplatin (80 mg/m² were submitted to a randomizedcontrolled trial to evaluate the effect of the combination ofmetoclopramide and dexamethasone for the treatment of delayedcisplatin-induced emesis occuring more than 24 hours after cisplatinadministration. All patients received intravenously (i.v.) high-dosemetoclopramide and dexamethasone on the day of cisplatin treatment.Excellent emetic control (no emesis during the 24 hours followingcisplatin administration) was achieved in 30 out of 41 patients(73%) with this combination. Patients treated i.v. with metoclopramideand dexarnethasone on days 2–7 experienced less delayedemesis, nausea and anorexia compared to those treated with aplacebo (delayed emesis, 25 vs 50%, respectively, P=0.105; morethan four days of nausea, 10 vs 35%, respectively, P=0.059;less than three days of anorexia, 80 vs 50%, respectively, P=0.048).Although the results of the study showed no statistically significantadvantage with the combination of i.v. metoclopramide and dexamethasonefor delayed emesis, we recommended the use of i.v. metoclopramideplus dexamethasone for patients treated with cisplatin, in viewof the short duration of anorexia and the marginal reductionin nausea. Female patients tended to have more emetic episodesand extrapyramidal side effects (except akathisia) than malepatients, but the differences were not statistically significantexcept for acute emesis (P<0.005)     

IEP与EP方案治疗小细胞肺癌的随机临床试验

目的　观察IEP方案与EP方案治疗小细胞肺癌的疗效和安全性。方法　 64例小细胞肺癌患者按随机数字表法分为IEP组和EP组 ,每组 3 2例。结果　 64例患者均可评价疗效和毒副反应。IEP组总有效率、局限期和广泛期有效率分别为 84.4%( 2 7/ 3 2 )、10 0 .0 %( 15 / 15 )和 70 .6%( 12 / 17) ,EP组分别为75 .0 %( 2 4/ 3 2 )、85 .7%( 12 / 14 )和 66.7%( 12 / 18) ,两组间比较均无显著性差异 (P >0 .0 5 )。IEP组中位缓解期和 1年生存率分别为 6月和 62 .5 %,EP组分别为 5月和 5 6.2 %(P >0 .0 5 )。两组共同的毒性反应为骨髓抑制 ,IEP组Ⅲ～Ⅳ度白细胞下降、恶心、呕吐、脱发发生率均明显高于EP组 (P <0 .0 1)。结论　IEP和EP方案均为治疗小细胞肺癌的有效方案 ,毒性反应可耐受。两方案临床疗效相似 ,均可作为治疗小细胞肺癌的一线方案。     

Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label,Randomized Controlled Trial

IntroductionThe phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses.MethodsA total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/m² every 3 weeks. Co-primary end points were overall survival (OS) in the intent-to-treat (ITT) and programmed death-ligand 1 (PD-L1) tumor cell expression greater than or equal to 25% populations. The exploratory biomarker analyses included PD-L1 expression, tumor mutation burden, and gene expression profile.ResultsAt the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p < 0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p < 0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1–4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified.ConclusionsTislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression.     

伊立替康联合顺铂方案与足叶乙甙联合顺铂方案治疗小细胞肺癌的随机对照临床研究

背景与目的 足叶乙甙＋顺铂（EP）方案是治疗小细胞肺癌（SCLC）的标准方案，本试验拟比较伊立替康＋顺铂（IP）方案与EP方案治疗SCLC的近期疗效和毒副作用。方法 61例SCLC患者被随机分组，接受IP或EP方案化疗2个周期以上，评价疗效及毒副作用。结果 ①IP组有效率为66．7％，完全缓解率为23．3％；EP组有效率为61．3％，完全缓解率为16．1％。两组近期疗效比较无显著性差异（P〉0．05）。②IP组Ⅲ～Ⅳ度白细胞下降2例（6．7％），EP组11例（35．5％），两组比较有显著性差异（P〈0．01）；IP组Ⅲ～Ⅳ度中性粒细胞下降2例（6．7％），EP组16例（51．6％），两组比较有显著性差异（P〈0．001）；IP组血小板减少8例（26．7％），EP组25例（80．6％），两组比较有显著性差异（P〈0．001）；IP组腹泻11例（36．7％），EP组2例（6．5％），两组比较有显著性差异（P〈0．01）；两组Ⅲ～Ⅳ度恶心呕吐比较无显著性差异（P〉0．05）；胆碱能综合征、肝肾功能异常、周围神经炎、脱发、静脉炎等均少见。结论 IP和EP方案是治疗SCLC有效的方案。与EP方案相比，IP方案疗效相似，而血液学毒性较轻，IP方案的腹泻毒性较明显，可以通过对症治疗控制。     

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study

Background.

In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy.

Methods.

Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded.

Results.

Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001).

Conclusion.

This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate.

Implications for Practice:

This large prospective multicenter study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show secondary adrenal suppression after antiemetic dexamethasone therapy. Adrenal suppression was particularly significant for patients cotreated with megestrol acetate. Clinicians need increased awareness of the potential for adrenal insufficiency secondary to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. These findings should help encourage prospective studies designed to determine the adequate doses and durations of antiemetic dexamethasone therapy required to reduce dexamethasone-related adverse effects while controlling chemotherapy-induced nausea and vomiting.     

98 例小细胞肺癌化疗疗效分析

 目的 比较CE方案（CBP、VP-16）、CAP方案（CTX、EPI、DDP）、CE-CAP交替方案治疗晚期小细胞肺癌（Smallcell1ungcancer，SCLC）的临床有效率及不良反应。方法 98例SCLC患者分别接受CE、CAP、CE-CAP交替方案化疗4个周期。结果 三种方案治疗的有效率分别为84．8％、80．4％和81％，差异无统计学意义。不良反应主要为骨髓抑制及消化道反应。骨髓抑制以白细胞减少为主，CE组白细胞Ⅲ度减少发生率为10．8％，CAP组发生率为9．7％，CE-CAP交替方案组9．5％，三组比较差异无统计学意义。消化道反应主要为恶心呕吐，CE组中出现Ⅲ～Ⅳ度胃肠道反应的为13％，CAP组中出现的为25．8％，CE．CAP组中出现的为23．8％，CE组和CAP组、CE-CAP组比较差异有统计学意义，而CAP组和CE-CAP组比较差异无统计学意义。结论 CE、CAP方案、CE-CAP交替化疗是治疗SCLC的较好方案，但CE方案胃肠道副作用较轻，耐受性较好，值得推荐。     

沙利度胺联合化疗治疗中国晚期非小细胞肺癌患者的随机对照试验Meta分析

  目的   通过Meta分析探讨沙利度胺联合化疗在晚期非小细胞肺癌患者中的应用价值。   方法  由两位独立评价者按相同检索策略检索中国生物医学文献库等资源中的文献,根据纳入标准筛选相关随机对照试验,评价研究质量后用RevMan 5.1软件进行分析,分析指标为有效率、临床获益率及不良反应。   结果  共纳入12项研究,总病例数691例。Meta分析显示:沙利度胺联合化疗组在有效率（OR=1.62,95%CI:1.18~2.22）及临床获益率（OR=2.05,95%CI:1.40~3.02）方面优于单纯化疗组。联合治疗组与单纯化疗组相比,血液学毒性发生率差异无统计学意义,恶心呕吐发生率低于后者（P=0.002）,外周神经毒性发生率有高于后者的趋势（P=0.05）,而便秘、乏力嗜睡、皮疹或瘙痒发生率高于后者（P值分别为0.002、0.000 2、0.001）。   结论  沙利度胺联合化疗可能提高中国患者的治疗有效率与临床获益率,但生存获益尚不明确。联合治疗不增加严重不良反应。      

紫杉醇联合顺铂治疗复发性小细胞肺癌

背景与目的小细胞肺癌对初次化疗极其敏感,但大多数患者会出现病情进展或复发,需要二线或挽救方案治疗。本研究的目的是观察紫杉醇联合顺铂治疗复发或进展的小细胞肺癌的疗效和安全性。方法紫杉醇联合顺铂治疗41例复发或进展的小细胞肺癌。紫杉醇175mg/m^2静脉滴注,第1天,顺铂30mg/m^2静脉滴注,第1-3天,每21天为一周期。结果39例可评价疗效,完全缓解率为12.8%（5/39）,部分缓解率为46.2%（18/39）,稳定率为33.3%（13/39）,进展率为7.7%（3/39）,有效率为59.0%。中位疾病进展时间为20周,中位生存期为27周,1年生存率为10.3%（4/39）。主要不良反应为血液学毒性,Ⅲ＋Ⅳ度白细胞下降率为24.4%（10/41）,无粒细胞减少性发热,Ⅲ度血小板下降率为4.9%（2/41）,无Ⅳ度下降。恶心呕吐发生率为82.9%（34/41）,仅3例为Ⅲ度毒性,无肾毒性及严重神经毒性。全组无毒性相关死亡病例。结论紫杉醇联合顺铂作为二线方案治疗复发的小细胞肺癌有较好的疗效,不良反应可以耐受。     

Randomized Control Study of Nedaplatin or Cisplatin Concomitant with Other Chemotherapy in the Treatment of Advanced Non-small Cell Lung Cancer

Objective: To observe the short-term efficacy, long-term survival time and adverse responses with nedaplatin(NDP) or cisplatin (DDP) concomitant with other chemotherapy in treating non-small cell lung cancer. Materialsand Methods: A retrospective, randomized, control study was conducted, in which 619 NSCLC patients in phasesⅢ and Ⅳ who were initially treated and re-treated were randomly divided into an NDP group (n=294) and a DDPgroup (n=325), the latter being regarded as controls. Chemotherapeutic protocols (CP/DP/GP/NP/TP) containingNDP or DDP were given to both groups. Patients in both groups were further divided to evaluate the clinicalefficacies according to initial and re-treatment stage, pathological pattern, type of combined chemotherapeuticprotocols, tumor stage and surgery. Results: The overall response rate (ORR) and disease control rate (DCR)in the NDP group were 48.6% and 95.2%, significantly higher than in the DDP group at 35.1% and 89.2%,respectively (P<0.01). In NSCLC patients with initial treatment, squamous carcinoma and phase Ⅲ, there weresignificant differences in ORR and DCR between the groups (P<0.05), while ORR was significant in patients withadenocarcinoma, GP/TP and in phase Ⅲa (P<0.05). There was also a significant difference in DCR in patientsin phase Ⅲb (P<0.05). According to the statistical analysis of survival time of all patients and of those in clinicalphase Ⅲ, the NDP group survived significantly longer than the DDP group (P<0.01). The rates of decreasedhemoglobin and increased creatinine, nausea and vomiting in the NDP group were evidently lower than in DDPgroup (P<0.05). Conclusion: NDP concomitant with other chemotherapy is effective for treating NSCLC, withhigher clinical efficacy than DDP concomitant with chemotherapy, with advantages in prolonging survival timeand reducing toxic and adverse responses.     

Efficacy of Aprepitant for Nausea in Patients with Head and Neck Cancer Receiving Daily Cisplatin Therapy

Background: Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin hasbeen demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonistduring daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant inpatients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy).Materials and Methods: Twenty patients with HNC were prospectively studied who received a triple antiemeticregimen comprising granisetron (40μg/kg on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125mg on day 1 and 80mg on days 2-5) with FP therapy (cisplatin 20 mg/m2 on days 1-4; 5-FU 400 mg/m2 on days1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimenexcept for aprepitant (control group). Results: For efficacy endpoints based on nausea, the aprepitant groupshowed significantly better results, including a higher rate of complete response (no vomiting and no salvagetherapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups withregard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adversereactions to aprepitant. Conclusions: This study suggested that a triple antiemetic regimen containing aprepitantis safe and effective for HNC patients receiving daily cisplatin therapy.     

Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy

IntroductionThe purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC).Patients and MethodsPatients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS).ResultsAll 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable).ConclusionIn patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy.     

吉西他滨联合顺铂治疗晚期NSCLC的疗效

背景与目的目前临床上对绝大多数晚期非小细胞肺癌患者缺乏有效的治疗方法和药物,本研究应用吉西他滨和顺铂两药联合化疗,观察该方案的临床疗效和毒副作用。方法对60例Ⅲ期及Ⅳ期的非小细胞肺癌患者给予吉西他滨1200mg/m2,第1、8天静脉输注;顺铂100mg/m2,第1天静脉输注或30mg/m2,第1、8天静脉输注。28天为一个周期,每例患者至少治疗2周期。结果全组完全缓解3例,部分缓解25例,无变化22例,进展10例,总有效率为46.67%。初治有效率为57.14%,复治为22.22%,差异有显著性(P<0.05)。毒性反应为白细胞减少和血小板减少,未影响到化疗的进行。结论吉西他滨联合顺铂治疗晚期非小细胞肺癌疗效较高,毒性可耐受。