大剂量异环磷酰胺治疗常规方案失效的软组织肉瘤

背景与目的:阿霉素(ADM)、氮烯咪氨(DTIC)、异环磷酰胺(IFO)为治疗进展期软组织肉瘤常用的化疗药物,但对ADM或常规剂量的IFO治疗失效的软组织肉瘤再化疗的有效方案甚少。本文探讨大剂量IFO治疗常规方案失效的软组织肉瘤的疗效及不良反应。方法:对15例常规ADM及IFO治疗失效的软组织肉瘤患者(10例进展期,5例术后化疗)采用IFO总量14g/m2持续静滴6天治疗。结果:进展期10例患者CR2例,PR2例,总有效率40%。随访4～48个月,中位生存期(21.00±3.29)个月,中位缓解时间(6.00±1.45)个月。主要不良反应为骨髓抑制,Ⅲ～Ⅳ度中性粒细胞减少占45.9%。结论:大剂量IFO治疗软组织肉瘤有效率较高,为常规ADM及IFO治疗失效后较好的挽救治疗方法。     

异环磷酰胺治疗头颈部软组织肉瘤的疗效观察

从1997年1月至1999年12月,共有12例头颈部软组织肉瘤患者在我院接受了以异环磷酰胺为主的联合化疗,现将应用此化疗方案治疗头颈部软组织肉瘤的疗效、毒性与应用中应注意的问题报道如下。     

异环磷酰胺在软组织肉瘤治疗中的地位

复习软组织肉瘤及骨肉瘤的化疗疗效。其中异环磷酰胺与阿霉素联合治疗175例,CR9％,总缓解率35％。提高两药剂量并加用GM—CSF共治疗111例,总缓解率46.5％,优于其他化疗方案。     

大剂量异环磷酰胺持续静滴联合阿霉素治疗进展期软组织肉瘤的临床观察

目的：评价大剂量异环磷酰胺持续７２ｈ静滴联合阿霉素治疗进展期软组织肉瘤的临床疗效和毒副反应。方法：２００８年３月～２００８年１０月收治进展期软组织肉瘤患者１５例,应用大剂量异环磷酰胺联合阿霉素治疗,异环磷酰胺总量１２ｇ／ｍ^２,持续静滴７２ｈ;阿霉素６０ｍｇ／ｍ^２第１天静滴。２１天为１周期。完成２～６周期,中位周期数为４。结果：全组患者ＣＲ１例（６.６７％）,ＰＲ１例（６.６７％）,ＳＤ１２例（８０.０％）,ＰＤ１例（６.６７％）,有效率１３.３％（２／１５）,疾病控制率９３.３％（１４／１５）。中位无疾病进展生存期６个月（３～１０个月）,中位总生存期７个月（３～１０个月）。主要毒副反应为粒细胞减少、胃肠道反应和脱发,其他毒副反应少见。结论：大剂量异环磷酰胺持续７２ｈ静脉滴注联合阿霉素方案治疗进展期软组织肉瘤可行,能够有效控制疾病进展,毒副反应可以耐受,值得进一步深入研究。     

标准剂量及大剂量异环磷酰胺单用或联合应用治疗肉瘤

本文介绍美国Dana Farber癌症研究所应用异环磷酰胺治疗肉瘤的经验。除试用标准剂量及大剂量异环磷酰胺治疗外,作者报告了MAID联合化疗方案(Mesna,Adriamycin Ifosfa-mide,DTIC)105例,11例获CR(10％)48例PR(47％),总缓解率57％。加用GM—CSF有骨髓保护作用。以大剂量异环磷酰胺、卡铂、VP—16加自身骨髓移植组疗效最好。     

异环磷酰胺,VP—16及顺铂治疗晚期软组织肉瘤

为了探讨异环磷酰胺联合化疗治疗软组织肉瘤的疗效,我们进行了Ⅱ期临床试验。36例有可测量病灶的残留、复发或转移性软组织肉瘤患者参加试验。化疗方案为DDP20mg/m~2第1至5天静注,VP_(-16) 75mg/m~2第1至5天静注,异环磷酰胺1.2g/m~2第1至5天静注,巯乙磺酸钠120mg/m~2在化疗开始时静注,然后按1.2g/m~2于第1至5天静注。每四周重复疗程。在24个可评价的患者中,1例获得CR(4％),8例获得PR(33％),中数生存期是14个月(1～34个月)。主要的毒性为骨髓抑制,多数病人有Ⅲ度或Ⅳ度中性粒细胞下降,没有治疗引起死亡的报道。此项研究的初步结果表明异环磷酰胺+VP_(-16)+DDP在晚期软组织肉瘤的治疗上是有效的。     

大剂量异环磷酰胺治疗进展期软组织肉瘤的疗效评价

目的：评价大剂量异环磷酰胺治疗进展期软组织肉瘤的临床疗效和不良反应。方法：进展期软组织肉瘤患者24例，异环磷酰胺总量14g／m^2持续灌注24h，第1～6天行常规美斯钠（mesna）解毒和水化，28d为1个周期，共完成1～4个周期，中位周期数为3。结果：全组患者CR3例（12．5％），PR8例（33．3％），SD8例（33．3％），PD5例（20．8％），总有效率45．8％（11／24）。接受一线和二线化疗患者为5例和19例，一线化疗3例获CR或PR；二线化疗8例获CR或PR。主要毒副反应为骨髓抑制，其白细胞Ⅲ～Ⅳ度下降发生率为51．4％，其他不良反应少见。结论：大剂量异环磷酰胺是治疗进展期软组织肉瘤有效化疗方案，患者缓解率较高，毒副反应可以耐受，值得临床进一步观察。     

异环磷酰胺联合表阿霉素治疗晚期软组织肉瘤27例疗效分析

目的观察异环磷酰胺（IFO）联合表阿霉素（EPI）方案治疗晚期软组织肉瘤（ASTS）的疗效与安全性。方法采用IFO＋EPI方案治疗ASTS 27例。IFO 6g/m^2,分d1～3静脉滴入或96 h持续静脉点滴;EPI 90 mg/m^2,分d1～3（或96 h持续静脉点滴）,21 d为1个周期。本组中位化疗周期数为3个（2～5个）。结果CR 0例,PR 5例,SD 13例,PD 9例,全组总有效率18.5%,临床获益率为66.7%,1年生存率为37.0%,2年生存率为11.1%。其中5例PR患者均为一线治疗,一线治疗有效率为23.8%（5/21）。主要毒性反应为骨髓抑制及胃肠道反应。结论EPI联合IFO治疗ASTS,使用方便、疗效确切、毒性反应较轻,该方案是ASTS有效解救治疗方案。     

异环磷酰胺、依托泊苷和顺铂联合方案治疗晚期软组织肉瘤

近年来发现异环磷酰胺 (ＩＦＯ)对软组织肉瘤疗效较好 ,单药有效率在 38% [1] ,我们自 1997年 6月— 1999年 10月 ,应用ＩＥＰ方案 [异环磷酰胺 (ＩＦＯ)、依托泊苷 (ＶＰ 16 )、顺铂(ＤＤＰ) ]治疗 6 4例晚期软组织肉瘤 (ＳＴＳ)病人 ,观察其疗效和毒副作用。材料和方法一　研究对象　 6 4例晚期ＳＴＳ病人 ,男 43例 ,年龄 2 2—76岁 ,中位年龄 42岁。纤维肉瘤 18例 ,滑膜肉瘤 15例 ,横纹肌肉瘤 17例 ,脂肪肉瘤 14例 ,其中初治病例 11例 ,复治病例 5 3例 ,均经病理证实 ,并有客观观察指标。治疗前预计生存期大于 3个月 ,Ｋａｒｎｏｆｓｋｙ…     

MAID方案治疗20例晚期软组织肉瘤的近期疗效分析

[目的]分析由表阿霉素（epirubicin，EPI）替代阿霉素（doxorubicin，ADM）的MAID方案治疗晚期软组织肉瘤（soft tissue sarcoma，STS）的疗效和毒副反应。[方法]采用MAID方案（IFO 1200mg／m^2，静滴4h，d1-4;美斯纳720mg/m^2，在IFO治疗0、4和8h静滴，d1-4;EPI 50mg／m^2～60mg／m^2，静滴，d1；DTIC 200mg／m^2，静滴，d1-4）治疗疗晚期STS患者20例。[结果]20例患者无CR；PR5例（25．0％）；SD7例（35．0％）；PD8例（40．0％）；临床获益率为60．0％。毒副反应以骨髓抑制，胃肠道反应和脱发为主。[结论]以EPI替代的MAID方案有一定的疗效，且毒副作用较小．可优先用于晚期STS患者的治疗。     

骨肉瘤的大剂量化疗

本文报告ＨＤＭＴＸＣＦＲ治疗原发性骨肉瘤１８例的临床疗效，所有病例除一例经Ｘ线诊断外，余经病理学确诊。ＭＴＸ每疗程剂量０．５～３．０／Ｍ￣２，静滴ＭＴＸ开始至ＣＦ解救时间为１６～１８小时，其毒副反应轻，无一例发生意外。骨肉瘤术后辅助化疗后２年生存率５５．６％，生存５年以上者３例。本文提示，骨肉瘤的辅助化疗有肯定疗效，ＨＤＭＴＸ为有效的辅助化疗方案之一，但剂量不宜过低，只要注意水化，尿碱化及ＣＦ解救，此疗法是安全的。     

Continuous-infusion Ifosfamide and Doxorubicin Combination as Second-Line Chemotherapy for Recurrent or Refractory Osteosarcoma Patients in China: a Retrospective Study

Objective: The aim of this retrospective study was to evaluate the feasibility and efficacy of response tocontinuous-infusion ifosfamide and doxorubicin combination as second-line chemotherapy for patients withrecurrent or refractory osteosarcoma. Materials and Methods: Eighteen recurrent or refractory osteosarcomapatients who were treated with continuous-infusion ifosfamide and doxorubicin combination between May 1999and April 2011 were included in the analysis. Ifosfamide at 12g/m2 was administered by intravenous continuousinfusion over 3 days, and doxorubicin 60mg/m2 was administered as an intravenous bolus injection on day 1. Thecombination therapy was repeated every 3 weeks. Treatment was continued until evidence of disease progressionor unacceptable toxicity. Results: The patients (ages 7-53 years) received a total of 42 cycles of chemotherapy(median: 2 courses; range: 2-5 courses). The overall response rate was 0% and the disease control rate was22.3%, with four patients having stable disease. The median time to progression and overall survival time were2 months (range: 2-5 months) and 9 months (range: 3-29 months), respectively. Major severe toxicities wereleucopenia 7 (38.9%), nausea and vomiting 3 (16.7%) and alopecia 9 (50%). There were no treatment-relateddeaths. Conclusions: In our experience, continuous-infusion ifosfamide and doxorubicin combination therapyat this dosage and schedule was found to be well tolerated and moderate effective, which could be consideredas salvage therapy for patients with recurrent or refractory osteosarcoma. Further assessment is necessary toconfirm the safety and efficacy of this treatment.     

Activity of Pazopanib and Trabectedin in Advanced Alveolar Soft Part Sarcoma

Background

Alveolar soft part sarcoma (ASPS) is an exceedingly rare and orphan disease, without active drugs approved in the front line. Pazopanib and trabectedin are licensed for sarcoma treatment from second‐line, but very little and contradictory data are available on their activity in ASPS. Lacking ongoing and/or planned clinical trials, we conducted a multi‐institutional study involving the reference sites for sarcoma in Europe, U.S., and Japan, within the World Sarcoma Network, to investigate the efficacy of pazopanib and trabectedin.

Materials and Methods

From May 2007, 14 of the 27 centers that were asked to retrospectively review their databases had identified 44 advanced ASPS patients treated with pazopanib and/or trabectedin. Response was evaluated by Response Evaluation Criteria in Solid Tumors 1.1. Progression‐free survival (PFS) and overall survival (OS) were computed by Kaplan‐Meier method.

Results

Among 30 patients who received pazopanib, 18 were pretreated (13 with other antiangiogenics). Response was evaluable in 29/30 patients. Best responses were 1 complete response, 7 partial response (PR), 17 stable disease (SD), and 4 progressions. At a 19‐month median follow‐up, median PFS was 13.6 months (range: 1.6–32.2+), with 59% of patients progression‐free at 1 year. Median OS was not reached. Among 23 patients treated with trabectedin, all were pretreated and evaluable for response. Best responses were 1 PR, 13 SD, and 9 progressions. At a 27‐month median follow‐up, median PFS was 3.7 months (range: 0.7–109), with 13% of patients progression‐free at 1 year. Median OS was 9.1 months.

Conclusion

The value of pazopanib in advanced ASPS is confirmed, with durable responses, whereas the value of trabectedin appears limited. These results are relevant to defining the best approach to advanced ASPS.

Implications for Practice

This retrospective study, conducted among the world reference centers for treatment of sarcoma, confirms the value of pazopanib in patients with advanced alveolar soft part sarcoma (ASPS), with dimensional and durable responses, whereas trabectedin shows a limited activity. Alveolar soft part sarcoma is resistant to conventional cytotoxic chemotherapy. Pazopanib and trabectedin are licensed for treatment of sarcoma from second line; in the lack of prospective clinical trials, these results are relevant to defining ASPS best management and strongly support initiatives aimed at obtaining the approval of pazopanib in the front line of the disease.     

Ifosfamide and doxorubicin combination chemotherapy for recurrent nasopharyngeal carcinoma patients

Background: We assessed the efficacy and toxicity of ifosfamide and doxorubicin combination chemotherapy(CT) regimen retrospectively in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC)previously treated with platinum-based chemotherapy. Methods: A total of thirty patients who had receivedcisplatin based chemotherapy/chemoradiotherapy as a primary treatment received ifosfamide 2500 mg/m2 days1-3, mesna 2500 mg/m2 days 1-3, doxorubicin 60 mg/m2 day 1 (IMA), repeated every 21 days. Eligible patientshad ECOG PS< 2, measurable recurrent or metastatic disease, with adequate renal, hepatic and hematologicfunctions. Results: Median age was 47 (min-max; 17-60). Twenty six (86.7 %) were male. Median cycles ofchemotherapy for each patient were 2 (range:1-6). Twenty patients were evaluable for toxicity and response. Nopatient achieved complete response, with nine partial responses for a response rate of 30.0% in evaluable patients.Stable disease, and disease progression were observed in five (16.7%) and six (20.0%) patients, respectively.Clinical benefit was 46.7%. Median time to progression was 4.0 months. Six patients had neutropenic fever afterIMA regimen and there were one treatment-related death due to tumor lysis syndrome in first cycle of the CT.No cardiotoxicity was observed after CT and treatments were generally well tolerated. Conclusion: Ifosfomideand doxorubicin combination is an effective regimen for patients with recurrent and metastatic NPC. For NPCpatients demonstrating failure of cisplatin based regimens, this CT combination may be considered as salvagetherapy.     

Combination Chemotherapy with Vinblastine, Ifosfamide and Cisplatin in Bulky Seminoma

Since 1982, 24 patients with bulky seminoma were treated with the VIP-regimen consisting of vinblastine 6 mg/m² days 1+2, ifosfamide 1.5 g/m² days 1-5, cisplatin 20 mg/m² days 1-5. One patient showed primary progression, another patient partial remission, and one patient died during the first cycle. All the other patients had complete remission (21/24=87%), which was documented histologically in 9 patients. One patient relapsed but obtained complete remission after repeated treatment. Thus 21 patients are currently living without disease after a median observation time of 30+ months. Bone marrow toxicity was severe, leading to dose reduction in more than 50% of the patients. No other severe side effects were observed. We conclude that the regimen is highly effective in bulky seminoma. Reduction of the vinblastine dose is recommended because of bone marrow toxicity.     

异环磷酰胺、顺铂、丝裂霉素C治疗非小细胞肺癌40例临床观察

应用异环磷酰胺联合顺铂、丝裂霉素C，治疗晚期不能手术的非小细胞肺癌40例，其中Ⅲ期27例，Ⅳ期13例；初治18例，复治22例。结果：有效率50.0％，Ⅲ期63.0％，Ⅳ期23．1％（P＜0．05）。初治组有效率66．7％，复治组31．6％（P＜0．05）。Ⅲ期疗效优于Ⅳ期，初治优于复治。主要毒副反应为胃肠道反应和骨髓抑制。     

Predictors of Chemotherapy Induced Adverse Events in Pediatric Osteosarcoma Patients

Objective: To investigate the prevalence of chemotherapy-induced adverse events and the associated risk factors in pediatric patients with osteosarcoma. Methods: This retrospective cross-sectional study enrolled 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) treated at Srinagarind Medical Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, between January 1, 2008 and December 31, 2018. The prevalence of major adverse events and a correlation between baseline characteristics and adverse events were analyzed using a generalized estimating equation model. Result: The prevalence of adverse events in 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) was determined as chemotherapy-induced nausea and vomiting (29.2%; n=296), hepatotoxicity (21.2%; n=215), anemia (70.69%; n=719), neutropenia (26.65%; n=271), and thrombocytopenia (13.65%; n=139). Factors associated with chemotherapy-induced hepatotoxicity included methotrexate dose ≥ 12 g/m2 (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.22–1.39; P<0.001), plasma concentration of methotrexate at 72 hours >0.1 μM (OR 1.22; 95% CI 1.19–1.25; P<0.001), and pre-hydration rate ≤ 125 mL/m2/h (OR 1.10; 95% CI 1.07–1.12; P<0.001). Conclusion: Major adverse events are becoming more common in pediatric osteosarcoma patients, and risk factors include larger chemotherapy doses, higher plasma methotrexate concentrations, and a slower pre-hydration rate. The outcomes of the study could aid in the better treatment of toxicity in children with osteosarcoma.     

Sex- and Age-Related Chemotherapy Toxicity in Patients with Non-Metastatic Osteosarcoma

Abstract

The influence of age and sex on chemotherapy-related toxicity was evaluated in children and adults with non metastatic osteosarcoma. Treatment consisted of methotrexate (MTX, 12 g/m²), cisplatin (CDP 120 mg/m²) and doxorubicin (ADM 75-90 mg/m²) and high-dose ifosfamide (HDIFO). Toxicity data from 1,051 courses (295 with MTX, 756 based on doxorubicin, cisplatin and high-dose ifosfamide) were analyzed. Children (4-14 yrs) and females showed a higher incidence of grade 4 neutropenia and thrombocytopenia and were more frequently hospitalized for neutropenic fever compared to adolescents and young adults (AYA, 15-19 yrs) and adults (>20-40 yrs). Delayed MTX excretion was higher in adults than AYA and children. Adults (up to 40 years) can be treated with pediatric protocols for osteosarcoma and they experience lower hematologic toxicity compared to pediatric population. Further investigations on sex-related susceptibility to chemotherapy in osteosarcoma patients are recommended.     

异环磷酰胺联合化疗治疗22例晚期肿瘤的近期疗效观察

对２２例经病理证实复发及不能手术或放疗的晚期恶性肿瘤病人采用以异环磷酰胺为主的联合化疗，结果是１例完全缓解。９例部分缓解，总缓解率（ＣＲ＋ＰＲ）４５．５％，主要毒副反应为骨髓抑制和胃肠道反应，未见心、肝、肾和中枢神经毒副反应。结果显示异环磷酰胺为主的联合化疗方案治疗晚期恶性肿瘤是行之有效的。