大剂量干扰素辅助治疗国人口腔粘膜恶性黑色素瘤的临床研究

目的 探讨大剂量干扰素辅助治疗口腔粘膜恶性黑色素瘤的疗效和安全性。方法 回顾性分析2004年5月至2012年11月我科经治的Ⅲ～ⅣA期口腔粘膜恶性黑色素瘤患者的治疗及预后情况。在经治的117例患者中,73例术后接受了大剂量干扰素α-2b治疗,其中有58例完成了治疗计划,设为治疗组,另15例中途停止;其余44例未采用大剂量干扰素治疗者作为对照组。比较两组患者的总生存期（OS）和无复发生存期（RFS）以及相关不良反应的发生情况。结果 117例患者的中位OS为40个月（95％CI：33～62个月）。治疗组与对照组中Ⅲ期患者的中位OS（69个月vs.65个月）和RFS（50个月 vs. 34个月）的差异均无统计学意义（P＞0.05）,治疗组与对照组中ⅣA期患者的中位OS（37个月 vs. 20个月）和中位RFS（33个月 vs. 10个月）的差异均有统计学意义（P＜0.05）,治疗组与对照组中Ⅳ期伴颈淋巴结转移患者的中位OS（40个月 vs. 20个月）和中位RFS（33个月 vs. 10个月）的差异均有统计学意义（P＜0.05）。大剂量干扰素治疗的常见血液学毒性为骨髓抑制,包括白细胞减少和血小板减少;非血液性不良反应包括流感样症状、恶心呕吐、肝功能损害等。全组患者不良反应以1～2级为主,仅有7例出现3～4级毒副反应,给予对症治疗后均能缓解,无治疗相关性死亡。结论 术后大剂量干扰素辅助治疗能显著提高ⅣA期口腔粘膜恶性黑色素瘤患者的OS和RFS,且治疗的不良反应可耐受。     

恶性黑色素瘤大剂量干扰素辅助治疗诱导期的耐受性观察

摘 要：［目的］ 观察恶性黑色素瘤患者术后大剂量干扰素辅助治疗诱导期的耐受性。［方法］ 回顾性分析2011年6月至2015年6月我院收治的203例AJCC ⅡB~Ⅲ期恶性黑色素瘤患者并接受术后大剂量α-2b干扰素辅助治疗,其中4周静脉诱导期剂量为1500万IU/m2,采用NCI-CTCAE 4.0评定诱导期药物相关不良事件,观察剂量限制性毒性相关事件和治疗中进展情况。［结果］ 全部203例患者诱导期均接受药物相关不良事件评价,共发生剂量限制性毒性34例次,主要为4级粒细胞减少（8.4%）和3级肝酶升高(4.4%)。21例患者遵循减量计划完成诱导,7例患者未完成诱导期治疗,原因包括3例进展,2例明显疲乏,1例重度肝功能不全和1例3级斑丘疹。1年大剂量干扰素治疗中共有42例进展,N3组复发转移率达50%。［结论］ 大剂量干扰素在中国人群中有较好的耐受性,但对于3个以上淋巴结转移的相对更高危患者,干扰素似乎有效率不高。     

重组干扰素α-2b抗肿瘤作用的Ⅱ期临床观察

本文报道了古巴重组干扰素α-2b(HU-rIFN alfa-2b)治疗70例恶性肿瘤的结果。IFN α-2b 用法为肌肉注射,每周2次,第一周3×10~6IU/次,第2周6×10~6 IU/次;第3至8周9×10~6IU/次。在62例可评价疗效的病人中,肾癌26例,1例 CR,1例 PR(有效比2/26);黑色素癌16例,2例 PR(2/16);恶性淋巴瘤7例,4例 PR(4/7);乳腺癌13例,2例 PR(2/13);总有效率为16.1%(10/62)。主要副作用为流感样症状。包括发热、寒战、乏力、肌痛、头晕等,还有不同程度的骨髓抑制及胃肠道反应。本组的结果提示,IFN α-2b 的毒性较小,可以初步考虑作为二线药物治疗肾癌、黑色素瘤和恶性淋巴瘤。     

干扰能瘤内注射治疗实体瘤疗效观察

本文报告我科1993．11～1994．11期间应用干扰能(α-2b干扰素)瘤内注射(A组)及瘤外注射(B组)治疗13例肿瘤患者，其中恶性黑色素瘤及恶性纤维组织细胞瘤各3例，横纹肌肉瘤2例，平滑肌肉瘤、软骨瘤及骨肉瘤各1例，转移低分化腺癌1例，乳癌骨转移1例。隔日注射一次，共3～4周，每次剂量依瘤体大小而定，A组共11例均显效。     

小剂量阿糖胞苷联合干扰素治疗慢性粒细胞白血病26例疗效分析

 　目的　探讨干扰素（IFNα-2b）持续或间隔用药联合小剂量阿糖胞苷（LD-Ara-C）治疗慢性粒细胞白血病（CML）的疗效。方法　对26例Ph+CML慢性期患者,经羟基脲（Hu）治疗,待WBC＜20×109／L时分组,12例采用IFNα-2b间隔用药+LD-Ara-C,IFNα-2b 300万U皮下注射,隔日1次,完全缓解（CR）后,2次／周,维持量1次／周,以14例IFNα-2b持续用药＋LD-Ara-C作对照,IFNα-2b 300万U皮下注射,1次／d,CR后隔日1次或3次／周,维持量1次／周或2次／周,LD-Ara-C均采用Ara-C 15 mg·m-2·d-1缓慢滴注,10 d／月。结果　治疗组完全细胞学缓解（CHR）9例,占75 %,12个月完全细胞遗传学缓解（CCR）1例,占9 %,微小细胞遗传学缓解（PCR）3例,占25 %,CCR+PCR为33.3 %,与持续用药组相比,差异无统计学意义,毒副作用轻。结论　IFNα-2b间隔用药+ LD-Ara-C治疗CML与IFN持续用药+LD-Ara-C疗效相当,毒副作用小,价格适中,值得在基层医院推广。     

局部晚期宫颈癌螺旋断层放疗同步化疗早晚期不良反应和疗效观察

目的：分析局部晚期宫颈癌螺旋断层调强（HT）放疗同步顺铂化疗和高剂量率（HDR）腔内照射的早晚期不良反应及疗效。方法选取接受根治性放疗的Ⅰb～Ⅲb宫颈癌患者46例。外照射采用HT-IMRT,14例盆腔淋巴结受累进行勾画定义为GTVnd,临床靶区（CTV）包括盆腔淋巴结区（6例扩大野包括腹主动脉旁淋巴结区）,GTVnd、全部子宫、宫颈及阴道,外扩0.8~1 cm构成计划靶区（PTV）。PTV中位剂量50.4 Gy（45～50.4 Gy）,常规分割;同步顺铂化疗,40 mg/m2/周;外照射30～40 Gy后联合HDR腔内照射,HDR的A点中位剂量30 Gy （30~36 Gy）,总的A点生物等效剂量（EQD2）90.3 Gy（84.9~98.3 Gy)。治疗期间每周及治疗后1~24个月评价不良反应及疗效。结果24例患者完成4～5周期同步化疗,22例患者仅完成2～3周期同步化疗。3级不良反应包括：白细胞减少9例（19.6%）,腹泻2例（4.3%）,恶心5例（10.9%）及呕吐1例（2.2%）;晚期3级不良反应2例：1例直肠出血,1例膀胱出血;无4级,5级不良反应发生。2年内无复发生存率、无病生存率及总生存率分别为91.7%、86.0%及97.1%。结论局部晚期宫颈癌螺旋断层调强放疗同步每周顺铂化疗联合HDR腔内照射,不良反应以血液学反应和恶心为主,晚期不良反应小,近期疗效较好。     

Ⅲ期非小细胞肺癌放疗加紫杉醇卡铂同步化疗的临床试验结果

目的探讨放疗结合紫杉醇或（和）卡铂同步化疗局部晚期非小细胞肺癌的副反应和疗效.方法41例Ⅲ期非小细胞肺癌患者（Ⅲa期17例,Ⅲb期24例）接受DT60～70Gy放疗,疗中给予45 mg/m^2紫杉醇（13例）或合用卡铂AUC=2（28例）,1次/周给药,共4～6周,放化疗在同一天开始进行.结果37例患者完成了60～72Gy放疗,2例放疗总量54Gy,2例56Gy.38例完成了4～6周化疗,3例完成了2周化疗.≥3级骨髓抑制2例,3级放射性食管炎4例,≥2级放射性肺炎6例,3级黏膜炎1例.全组总有效率（CR＋PR）78%.中位随访期17.2个月,中位生存期16.5个月,1、2、3年生存率分别为69%、34%和34%.放疗剂量＞66Gy与≤66Gy的中位生存期分别为13.2、36.8个月（P=0.027）.中位无局部复发生存期57.8个月,1、2年无局部复发生存率分别为85%、85%.失败原因照射野内复发4例,照射野外1例,照射野内＋野外1例,癌性胸水2例,远处转移12例.结论紫杉醇或（和）卡铂同步放化疗局部晚期非小细胞肺癌患者副反应可接受,具有较好的近期和远期疗效,失败原因主要为远处转移.放疗剂量高者疗效较好.     

大剂量干扰素治疗是黑素瘤术后辅助治疗的首选方案（附450例观察）

目的:回顾分析黑素瘤患者术后辅助治疗的临床资料,评价不同的术后辅助治疗方案对患者无病生存(disease-free survival,DFS)的影响。方法:收集2006年1月至2009年7月我科就诊的450例Ⅰ至Ⅲ期恶性黑素瘤患者(来自全国28个省市,男239、女211例,年龄12～85岁,中位年龄51岁)的临床资料。所有患者均接受手术治疗,术后辅助治疗包括大剂量干扰素治疗(2 200万IU静注,每周5次,共4周;900万IU皮下注射,每周3次,共11个月)、化疗(方案以达卡巴嗪或替莫唑胺为主,也有联合顺铂、紫杉醇、长春新碱等药物的方案)、化疗联合放疗和单纯放疗(原发灶或淋巴结引流区域放疗,剂量40～60 Gy)等4个方案。结果:450例Ⅰ至Ⅲ期恶性黑素瘤患者,分别行原发病灶的局部切除、扩大切除或扩大切除联合区域淋巴结切除。术后184例患者未接受任何治疗、84例患者接受了化疗、25例患者接受了联合放化疗、2例患者接受了单纯放疗,该4组患者的中位DFS分别为13个月、20个月、29个月、23个月;而155例接受了大剂量干扰素治疗患者的中位DFS尚未达到。化疗的不良反应主要为消化道不良反应、骨髓抑制、肝功能损伤等;干扰素治疗的不良反应主要有白细胞降低、发热、乏力、转氨酶升高、厌食,其中白细胞降低以及转氨酶升高达3或4级不良反应的发生率分别为15%和10%;经对症处理后,患者的不良反应均恢复正常。结论:Ⅰ至Ⅲ期恶性黑素瘤患者的手术切除方式以及术后辅助治疗的方案对于患者的DFS极为重要,术后接受大剂量干扰素治疗延长恶性黑素瘤患者DFS的效果最好,且安全性较好。     

周剂量紫杉醇联合顺铂同步调强放疗治疗局部晚期食管癌的疗效分析

目的 探讨周剂量紫杉醇联合顺铂同步调强放疗（IMRT）治疗局部晚期食管癌的疗效及安全性。方法 2010年1月至2015年4月36例初诊局部晚期食管癌患者接受周剂量紫杉醇联合顺铂同步IMRT治疗,具体方案：紫杉醇50 mg／m2静滴,顺铂25 mg／m2静滴,均为每周1次;IMRT：60 Gy／30次,每周5次。采用RECIST 1.1版标准评价客观疗效,采用国立癌症研究所毒性判定标准（NCI CTC）4.0评价化疗毒性反应,同时随访其生存情况。结果 29例（80.6％）患者完成了治疗计划,36例患者均可评价疗效,其中17例获CR,13例PR,4例SD,2例PD,有效率和疾病控制率分别为83.3％和94.4％;中位无进展生存期为13.0个月,中位总生存期为250个月,1、2、3年生存率分别为77.8％、639％和33.3％。3级以上毒性反应包括白细胞减少（25.0％）、粒缺性发热（11.1％）、厌食（27.8％）和食管炎（25.0％）。结论 周剂量紫杉醇联合顺铂同步IMRT治疗局部晚期食管癌的疗效确切,不良反应可以耐受,是一种有前景的治疗方案。     

周剂量多西紫杉醇联合顺铂、氟尿嘧啶二线治疗晚期胃癌32例

[目的]研究周剂量多西紫杉醇（TXT）联合顺铂（DDP）、氟尿嘧啶（5-Fu）持续滴注二线治疗晚期胃癌的疗效和不良反应。[方法]32例晚期胃癌患者接受DCF方案二线化疗：TXT30mg/m2,d1,8,15,DDP25mg/m2,d1～3,5-Fu500mg/m2持续静脉滴注,d1～5,28d为1个周期。至少完成2个周期后评价有效率、不良反应、疾病进展时间（TTP）和总生存时间（OS）。[结果]32例患者均可评价疗效,客观缓解率21.9%（7/32）,中位TTP及OS分别为2.7个月和7.6个月。主要不良反应为骨髓抑制、胃肠道反应和脱发。[结论]周剂量TXT联合DDP、5-Fu持续滴注二线治疗晚期胃癌疗效显著,不良反应可以耐受。     

Health management program: factors influencing completion of therapy with high-dose interferon alfa-2b for high-risk melanoma

The goal of the 1-year observational, multicentre, open-label study reported here was to identify factors influencing adherence to high-dose interferon alfa-2b adjuvant therapy in patients at high risk of recurrence following surgical excision of malignant melanoma. The study was carried out in 23 tertiary-care centres across Canada.The 225 patients enrolled in the study all had malignant melanoma that was surgically excised and that required adjuvant treatment with interferon alfa-2b. Of these patients, 64% were men. Mean age was 51.7 years. All patients received interferon alfa-2b treatment during a 4-week induction phase (20 MU/m(2) intravenously 5 days per week) followed by a 48-week maintenance phase (10 MU/m(2) subcutaneously 3 days per week).Oncology nurses reviewed side-effect management with the patients before the induction and maintenance phases. Patients were provided with daily diaries, comprehensive educational materials, and ongoing nursing support. Data on side effects and discontinuations were obtained from patient interviews and diaries. THE MAIN OUTCOME MEASUREMENTS WERE RELATED TO TREATMENT DISCONTINUATION: rate, timing, reason, and prevention. Of the 225 patients, 75 (33.3%) discontinued interferon during the induction phase, and 58 (25.8%) discontinued during the maintenance phase. The main reasons for discontinuation were adverse events (58%) and disease progression (26%). Patients with a daily fluid intake greater than 1.5 L were more likely to complete therapy than were those with an intake less than 1.5 L (64% vs. 36%, p < 0.0001).Of 225 patients enrolled in the interferon alfa-2b health management program, 41% completed the 1-year treatment course. Higher fluid intake (>1.5 L daily) was associated with increased adherence to therapy.     

Temozolomide in combination with interferon alpha-2b in patients with metastatic melanoma: a phase I dose-escalation study

BACKGROUND: Metastatic melanoma (MM) is associated with a high risk of central nervous system (CNS) metastases, and current chemotherapy does not adequately treat or protect patients with MM against CNS metastases. Therefore, the authors initiated a Phase I study to determine the pharmacokinetics and safety profile of temozolomide (TMZ), a novel oral alkylating agent known to cross the blood-brain barrier, in combination with interferon alpha-2b (IFN-alpha2b). METHODS: Twenty-three patients with MM were enrolled in this single-center, open-label study. Patients with CNS metastasis were excluded. One cohort (n = 6 patients) received oral TMZ (200 mg/m(2) per day) for 5 days every 28-day cycle plus subcutaneous IFN-alpha2b (5 million International Units [MIU]/m(2) per day, 3 times per week). A second cohort (n = 17 patients) received TMZ 150 mg/m(2) per day on the same schedule plus escalating doses of IFN-alpha2b (5.0 MIU/m(2) per day, 7.5 MIU/m(2) per day, and 10 MIU/m(2) per day 3 times per week). RESULTS: The most common adverse events were fatigue, fever, nausea/emesis, anxiety, and diarrhea. Most toxicity was mild to moderate in severity. The primary dose-limiting toxicity was thrombocytopenia. The maximum tolerated dose was either TMZ 150 mg/m(2) plus IFN-alpha2b 7.5 MIU/m(2) or TMZ 200 mg/m(2) plus IFN-alpha2b 5.0 MIU/m(2). Four patients (17%) had objective responses (one complete response and three partial responses), and four patients had stable disease. The median survival was 9 months. The pharmacokinetics of TMZ were not affected by coadministration of IFN-alpha2b. CONCLUSIONS: TMZ can be combined safely with IFN-alpha2b. This regimen demonstrated clinical activity in patients with MM and merits further investigation to define its effect on the incidence of brain metastases.     

A phase II evaluation of all-trans-retinoic acid plus interferon alfa-2a in stage IV melanoma: a Southwest Oncology Group study

BACKGROUND: Interferon alfa has modest but definite activity in the treatment of metastatic melanoma and is the only agent currently available for adjuvant therapy of high-risk resected disease. A variety of retinoic acid derivatives have been shown to be synergistic with interferon alfa in vitro and in vivo, with nonoverlapping toxicities. If promising combinations of interferon alfa and retinoids could be developed for melanoma patients, they would have clinical relevance for the treatment of advanced as well as localized disease. PURPOSE: To determine the efficacy and toxicity of a combination of interferon alfa-2a and all-trans-retinoic acid in patients with measurable metastatic melanoma, the South-west Oncology Group conducted a phase II clinical trial. PATIENTS AND METHODS: Fifty-seven patients with measurable metastatic melanoma (American Joint Committee on Cancer stage IV) were entered; five patients were unevaluable. Treatment consisted of oral all-trans-retinoic acid (37.5 to 75 mg/m2 orally twice daily for 21 days followed by 7 days' rest) plus subcutaneously administered interferon alfa-2a (6 MU/m2 three times a week). RESULTS: Two complete and three partial responses were observed among 52 evaluable patients, for an objective response rate of 10% (95% confidence interval 3% to 21%). Responses were seen only in patients with pulmonary, nodal, or subcutaneous metastases, and lasted from 4 to 23+ months. Median survival for the 52 patients was 8 months. Side effects were tolerable but significant, with one case of grade IV anemia and 92% of patients experiencing at least grade II toxicity. Flu-like symptoms were the most commonly reported side effects. There was one case of grade III hyperlipidemia. CONCLUSION: The combination of recombinant human interferon alfa-2a with all-trans-retinoic acid did not result in a greater percentage of objective responses or a longer overall survival than that associated with interferon alfa alone. This combination cannot be recommended for further evaluation in melanoma in either the advanced disease or the adjuvant settings.     

Adjuvant pegylated interferon α-2b therapy for melanoma

Although adjuvant high-dose interferon α-2b therapy significantly improves recurrence-free survival vs. observation in high-risk resected melanoma, the overall survival benefit is presently unclear. Pegylation of interferon α-2b (peginterferon α-2b) allows for a reduction in the dosing frequency with increased drug exposure. Adjuvant peginterferon α-2b therapy has also been shown to provide a significant, sustained improvement in recurrence-free survival compared with observation in patients with stage III melanoma. We report on the use of adjuvant peginterferon α-2b (3 μg/kg/week) in clinical practice in a series of 8 patients treated at the Universit?tsklinikum Essen in Germany following complete resection of primary melanoma at intermediate- and high-risk of recurrence (stage II-III). Treatment duration ranged from 2 to 29 months, with 4 patients receiving long-term therapy (≥24 months). Following treatment, 5 patients (stage II) remained disease-free at 33, 33, 37, 39 and 43 months from the time of diagnosis. In 2 patients, peginterferon α-2b was terminated 4 and 9 months after treatment initiation due to disease progression. Once-weekly subcutaneous administration of peginterferon α-2b was convenient in all patients. In 3 patients experiencing adverse events, dose reductions led to a resolution of symptoms and enabled treatment to continue long-term. Three further patients discontinued therapy due to adverse events at 2, 8 and 27 months of therapy (persistent elevation of γ-glutamyl transpeptidase, liver transaminase elevation and urosepsis); dose modifications were not applicable in these patients. Thus, long-term adjuvant peginterferon α-2b therapy was feasible in the clinical practice setting and was generally well tolerated in these intermediate- and high-risk melanoma patients.     

Randomized phase II study of temozolomide given every 8 hours or daily with either interferon alfa-2b or thalidomide in metastatic malignant melanoma

PURPOSE: Temozolomide is an imidazotetrazine with a mechanism of action similar to dacarbazine and equivalent activity in melanoma. It is well tolerated and is a candidate for combination chemotherapy and schedule manipulation. In this study, we combined temozolomide with interferon alfa-2b and, separately, with thalidomide, and we administered temozolomide alone in a compressed schedule. The objectives of this randomized phase II, two-center study were to determine response rates, overall survival, and tolerability of the regimens in patients with advanced metastatic melanoma. PATIENTS AND METHODS: One hundred eighty-one patients with metastatic melanoma were randomly assigned to receive up to six 4-weekly cycles consisting of temozolomide 200 mg/m2 every 8 hours for five doses, or temozolomide 200 mg/m2 daily for days 1 to 5 plus interferon alfa-2b 5 MU (million International Units) subcutaneously three times a week, or temozolomide 150 mg/m2 (increased after one cycle to 200 mg/m2) daily on days 1 to 5 plus thalidomide 100 mg daily days 1 to 28. RESULTS: The treatment arms were well balanced for known prognostic factors. Median survival was 5.3 months for 8-hourly temozolomide, 7.7 months for temozolomide/interferon, and 7.3 months for temozolomide/thalidomide; and 1-year survivals were 18%, 26%, and 24%, respectively. Response or disease stabilization occurred in 20% of patients (95% confidence interval [CI], 10% to 33%) given 8-hourly temozolomide, 21% (95% CI, 12% to 33%) given temozolomide/interferon, and 25% (95% CI, 15% to 38%) given temozolomide/thalidomide. Grade 3 or 4 nonhematologic toxicities were similar in each arm except for infection, which was more frequent with 8-hourly temozolomide. There were fewer instances of grade 3 or 4 myelotoxicity with temozolomide/thalidomide. CONCLUSION: Of the three regimens tested, the combination of temozolomide and thalidomide seems the most promising for future study.     

Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial.

PURPOSE: The addition of cytokines to chemotherapy has produced encouraging results in advanced melanoma. In this phase III trial, we compared the effects of chemotherapy (cisplatin, vinblastine, and dacarbazine [CVD]) with those of sequential biochemotherapy consisting of CVD plus interleukin-2 and interferon alfa-2b. PATIENTS AND METHODS: Metastatic melanoma patients who had not previously received chemotherapy were stratified by prognostic factors and given chemotherapy or biochemotherapy. CVD consisted of dacarbazine (days 1 and 22) and cisplatin and vinblastine (days 1 to 4 and 22 to 25). Biochemotherapy involved CVD with vinblastine reduced 25% plus interleukin-2 by 24-hour continuous infusion (on days 5 to 8, 17 to 20, and 26 to 29) and interferon alfa-2b by subcutaneous injection (on days 5 to 9, 17 to 21, and 26 to 30). Response was assessed every 6 weeks. RESULTS: Among 190 patients enrolled, 91 were assessable for biochemotherapy and 92 for chemotherapy. Ten percent of the patients were alive a median of 52 months from start of therapy. Response rates were 48% for biochemotherapy and 25% for chemotherapy (P =.001); six patients given biochemotherapy and two given chemotherapy had complete responses. Median time to progression (TTP) was 4.9 months for biochemotherapy and 2.4 months for chemotherapy (P =.008); median survival was 11.9 and 9.2 months, respectively (P =.06). The influence of treatment on TTP and survival was confirmed in multivariate analyses with other prognostic factors not included in the original stratification. Biochemotherapy produced substantially more constitutional, hemodynamic, and myelosuppressive toxic effects. CONCLUSION: Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.     

达拉非尼联合曲美替尼用于24例恶性黑色素瘤辅助治疗的回顾性分析

背景与目的：恶性黑色素瘤是最致命的皮肤恶性肿瘤。Ⅲ期黑色素瘤术后复发的风险相对较高，本文回顾性分析了达拉非尼联合曲美替尼作为辅助治疗对携带有BRAF突变的中国Ⅲ期恶性黑色素瘤患者的疗效及安全性。方法：回顾性分析2019年8月—2022年4月在浙江省肿瘤医院收治的24例接受曲美替尼联合达拉非尼辅助治疗的Ⅲ期皮肤及肢端恶性黑色素瘤的患者。结果：在24例患者中，7例为黑色素瘤ⅢB期，11例为ⅢC期，3例为ⅢD期，3例为Ⅲ期（具体分期不明）。截至2022年10月1日，有12例（50.0%）患者完成了1年的辅助治疗。全部24例患者中有5例（20.8%）报告肿瘤复发。1年无复发生存（relapse-free survival，RFS）率为76.2%（95% CI：65.2% ~ 87.2%）。在皮肤黑色素瘤亚组中，1年RFS率为81.6%（95% CI：71.6% ~ 91.6%）。2例在辅助治疗期间复发，3例患者在完成治疗方案后复发。20例患者（83.3%）报告了至少一次不良事件，其中7例患者（29.2%）发生了3级或4级的严重不良反应。最常见的不良反应是发热、疲劳和恶心。有4例患者发生了脂膜炎，主要累及大腿及上肢。1例患者（4.2%）因不良事件导致永久停药，2例患者（8.3%）因不良事件导致剂量调整，7例患者（29.2%）因不良事件导致用药中断。结论：本研究结果显示，达拉非尼联合曲美替尼辅助治疗可使BRAF ^V600突变的Ⅲ期黑色素瘤患者短期获益，耐受性良好。     

Pegylated interferon alfa-2b treatment for patients with solid tumors: a phase I/II study.

PURPOSE: The efficacy of interferon alfa has been established in treating advanced melanoma and renal cell carcinoma (RCC) patients. We conducted a phase I/II study to determine the maximum-tolerated dose (MTD), the safety and tolerability, and the preliminary efficacy of once-weekly pegylated interferon alfa-2b (IFNalpha-2b) in patients with advanced solid tumors (primarily RCC). PATIENTS AND METHODS: To determine the MTD, 35 patients with a variety of advanced solid tumors received 0.75 to 7.5 micro g/kg/wk of pegylated IFNalpha-2b by subcutaneous injection for 12 weeks. An additional 35 previously untreated RCC patients received 6.0 and 7.5 micro g/kg/wk for up to 12 weeks. Patients with a response or stable disease after 12 weeks were eligible for the extension protocol and were treated for up to 1 year or until disease progression. RESULTS: The MTD for pegylated IFNalpha-2b at 12 weeks was 6.0 micro g/kg/wk. One year of 6.0 micro g/kg/wk was well tolerated with appropriate dose modification; no grade 3 or 4 fatigue occurred, and safety was comparable with that with nonpegylated IFNalpha-2b. The most common nonhematologic adverse events included mild to moderate nausea, anorexia, and fatigue. Six patients had grade 3 or 4 hematologic toxicity. Twenty-nine patients continued on the extension protocol. Four patients had a complete response, and five patients had a partial response. Among 44 previously untreated RCC patients, the objective response rate was 14%. Median survival for all RCC patients was 13.2 months. CONCLUSION: Pegylated IFNalpha-2b was active and well tolerated in patients with metastatic solid tumors, including RCC, at doses up to 6.0 micro g/kg/wk.     

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.     

High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696.

PURPOSE: High-dose interferon alfa-2b (IFNalpha2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNalpha2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNalpha2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNalpha2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies. PATIENTS AND METHODS: This trial enrolled 107 patients with resectable high- or very high-risk melanoma (AJCC stages IIB, III, and IV). RESULTS: The results demonstrate that IFNalpha2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNalpha2b and GMK is well tolerated in this patient population. CONCLUSION: Cox analysis of the results of the combination with IFNalpha2b show improvement in the relapse-free survival of patients with very high-risk melanoma (including those with resectable M1 disease).