Iressa治疗复发或转移性头颈鳞状细胞癌的临床研究

目的:探讨Iressa治疗复发或转移性头颈鳞状细胞癌的疗效和安全性。方法:对接受过二线化疗方案(至少一个化疗方案包括铂类)失败的复发或转移性头颈鳞状细胞癌患者,给予Iressa每日250mg口服,持续到患者出现不可接受的不良反应或疾病进展。结果:15例患者入组,Iressa 250mg日/口服治疗能够很好耐受,只出现1级和2级不良反应,但全组无1例患者获得部分反应或全消,中位疾病进展时间为4个月,中位总生存时间为16个月。结论:Iressa能够很好耐受,但是该组患者有效率很低,它在头颈鳞状细胞癌的使用除临床研究外不推荐使用。     

低剂量阿帕替尼联合替吉奥治疗铂类方案失败复发或转移性头颈部鳞状细胞癌的临床观察

目的观察低剂量阿帕替尼联合替吉奥治疗铂类方案失败复发或转移性头颈部鳞状细胞癌(HNSCC)的近期疗效及患者不良反应。方法回顾性分析江苏省连云港市第二人民医院2017年3月至2019年2月收治的26例铂类方案失败复发或转移性HNSCC患者,口服阿帕替尼250 mg/d,替吉奥每天60 mg/m2,分早晚2次口服,第1天至第14天,休息7 d,每21 d为1个周期,完成2个周期进行疗效评价,并观察患者不良反应。结果26例患者中,无完全缓解,部分缓解4例,疾病稳定16例,疾病进展6例。客观缓解率为15.3%(4/26),疾病控制率为76.9%(20/26),中位无进展生存期为3.8个月(2.1~6.3个月),患者不良反应主要是高血压、血小板下降、乏力等。结论低剂量阿帕替尼联合替吉奥治疗铂类方案失败复发或转移性HNSCC近期疗效较好,患者不良反应可耐受,有潜在临床推广应用价值。     

洛铂对头颈鳞状细胞癌细胞株增殖抑制作用的体外研究

化疗是复发转移性头颈鳞状细胞癌的主要治疗手段之一.含顺铂(DDP)的化疗方案是目前一线标准方案.洛铂(LBP)是最新的第3代铂类抗肿瘤药物,研究发现LBP对口腔鳞状细胞癌、喉癌和鼻咽癌有明显抗肿瘤活性,其中LBP单药或联合吉西他滨治疗复发转移性鼻咽癌的疗效与DDP相近,但不良反应更加轻微,患者耐受性更好,提示LBP在头颈鳞状细胞癌治疗中可能具有良好的应用前景[1-3].本研究通过体外实验,观察洛铂对头颈鳞状细胞癌细胞株增殖的抑制作用,以期初步探索LBP治疗头颈鳞状细胞癌的理论依据.     

吉非替尼治疗31例男性晚期非小细胞肺癌临床观察

目的：观察吉非替尼（Iressa）对男性晚期非小细胞肺癌（NSCLC）患者疗效及毒副反应。方法：31例经病理组织学或细胞学确诊的男性晚期NSCLC口服Iressa250mg/d,直至病灶进展或出现不可耐受的副反应,每月CT扫描,评价疗效,同时记录不良反应。结果：31例入选患者中,30例可评价疗效,无完全缓解（CR）,部分缓解（PR）6例,均为肺腺癌,稳定（SD）12例,其中鳞癌1例,12例病情进展（PD）,有效率（RR）为20%（6/30）,疾病控制率（CR＋PR＋SD）为60%（18/30）,中位肿瘤进展时间5个月,1年生存率40%。最常见的毒副反应为皮疹和腹泻。结论：对于无法耐受化疗或化疗失败的亚洲男性晚期NSCLC患者,尤其是肺腺癌患者,持续口服吉非替尼同样是较理想的方案。     

贝伐珠单抗联合紫杉类药物一线治疗局部复发或转移性乳腺癌患者的安全性及疗效

[目的]研究贝伐珠单抗联合紫杉类药物一线治疗Her-2阴性的局部复发或转移性乳腺癌患者的安全性和疗效。[方法]32例Her-2阴性的复发或转移性乳腺癌患者,一线接受贝伐珠单抗联合紫杉类方案的化疗,直至疾病进展或不良反应不能耐受或患者要求出组。研究者选择化疗方案：贝伐珠单抗15mg／kg静滴d1,多西他赛75mg／m^2,静滴d1,21d为一个周期;或贝伐珠单抗10mg／kg静滴d1,15紫杉醇80mg／m^2,静滴d1,8,15,为一个周期。每3个周期评价疗效。[结果]32例可评价疗效和副作用,PR16例,SD15例,PD1例,总有效率50％,中位TTP为7.25个月。3级以上不良反应为阴道出血、粒细胞下降以及腹泻。[结论]贝伐珠单抗联合紫杉类药物治疗晚期乳腺癌不良反应可以耐受,具有一定疗效。     

卡培他滨维持治疗转移性乳腺癌的临床观察

目的观察应用卡培他滨维持治疗转移性乳腺癌患者的疗效及不良反应。方法对一线化疗疾病获得控制的晚期转移性乳腺癌患者,给予卡培他滨单药维持化疗直至疾病进展,具体给药方案:1000 mg/m2口服,每天2次,第1~14天持续给药,每3周重复。结果 30例转移性乳腺癌患者共完成维持化疗124个周期,中位无进展生存时间(MPFS)为6.8个月(2.9~19.0个月)。主要不良反应为手足综合征和白细胞减少,但均可耐受。结论转移性乳腺癌患者给予卡培他滨维持治疗,可明显延长患者的无进展生存期,同时不良反应均可耐受。     

吉非替尼治疗晚期难治性非小细胞肺癌六例的临床观察

观察Iressa治疗晚期难治非小细胞肺癌(non-small cell lungcancer,NSCLC)的近期疗效及毒副反应,选择6例住院的Ⅳ期非小细胞肺癌患者进行治疗观察。6例患者均接受≥6个周期含铂类药物的联合化疗后病情进展(PD)或复发者。治疗方案为Iressa单药口服250mg,1次/d,直至死亡或出现严重不良反应或病灶进展。每月1次胸部CT扫描评价疗效。6例患者中2例部分缓解(PR),3例病情稳定(SD),1例进展(PD)。4例症状缓解,缓解最明显的症状为憋气、咳嗽和疼痛,出现症状缓解的中位时间为14d。最常见的毒副反应为易于控制和逆转的皮疹和腹泻。     

紫杉醇、卡铂和5-氟尿嘧啶联合时辰化疗方案对转移或复发口腔鳞状细胞癌的疗效分析

目的 研究紫杉醇、卡铂和5-氟尿嘧啶联合时辰化疗方案和传统治疗方案对转移或复发口腔鳞状细胞癌的临床治疗效果.方法 对50例患有复发和(或)转移口腔鳞状细胞癌患者,采用紫杉醇、卡铂和5-氟尿嘧啶进行姑息化疗,根据给药时间的不同,将其分为传统化疗组(25例)和时辰化疗组(25例).对比2组患者治疗后的有效率、中位总生存率、中位无进展生存时间以及不良反应发生率.结果 在有效率以及中位总生存时间方面,时辰化疗组显著高于传统化疗组(P＜0.05).通过治疗后随访发现,Ⅲ～Ⅳ级不良反应发生率以及总不良反应发生率上,时辰化疗组均明显低于传统化疗组(P＜0.05).结论 采用紫杉醇、卡铂和5-氟尿嘧啶联合时辰化疗方案对转移或复发口腔鳞状细胞癌患者进行治疗,在提高治疗有效率、延长患者生存时间以及降低不良反应方面具有积极的意义.     

多西他赛联合卡培他滨二线治疗晚期食管鳞状细胞癌的Ⅱ期研究

目的 研究多西他赛联合卡培他滨二线治疗晚期食管鳞状细胞癌的疗效、患者不良反应、至疾病进展时间（TTP）和总生存（OS）.方法 30例一线治疗失败的晚期食管鳞状细胞癌患者接受多西他赛60 mg/m2,第1天,静脉滴注1h;卡培他滨每天825 mg/m2,分2次口服,第1天至第14天;21d为1个周期,最多不超过6个周期.结果 30例患者接受中位2个周期（2～6个周期）化疗.中位随访时间15.4个月（3.0 ～ 31.5个月）.疗效评价为部分缓解7例（23.3％）,稳定13例（43.3％）.中位TTP为3.0个月（95％CI 1.929 ～ 4.071）,中位OS为8.3个月（95％CI 6.848 ～ 9.752）.严重（3/4级）不良反应为中性粒细胞减少10例,贫血5例,血小板减少3例,手足综合征4例和疲乏3例.结论 多西他赛联合卡培他滨对一线治疗失败的晚期食管鳞状细胞癌患者有效,不良反应可接受,可考虑作为治疗晚期食管鳞状细胞癌的二线化疗方案.     

吉西他滨联合顺铂治疗头颈部癌52例分析

目的 评价吉西他滨联合顺铂治疗复发转移性头颈部癌患者的疗效和毒性。方法 52例复发转移性头颈部癌患者接受吉西他滨联合顺铂方案：吉西他滨1000mg／m^2,第1天和第8天;顺铂25mg／m^2,第1～3天;21d为1个疗程。结果 可评价患者52例,3例（5．8％）达完全缓解,19例（36．5％）达部分缓解,有效率42．3％（22／52）。中位疾病进展时间5．0个月,中位生存期9．9个月,1年生存率为43．4％。在既往经含铂方案化疗的32例患者中,2例（6．3％）达完全缓解,11例（34．4％）达部分缓解,有效率为40．6％（13／32）。中位疾病进展时间3．4个月,中位生存期8．3个月,1年生存率为29．2％。主要不良反应为1或2度血液学毒性、皮疹和恶心呕吐。结论 吉西他滨联合顺铂是治疗晚期复发转移性头颈部癌患者安全、有效的联合化疗方案．     

Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma

Background: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of ∼30% and median survival of 6 months.Patients and methods: In a multicentre phase II study, 32 patients with recurrent or metastatic HNSCC received 3-AP Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), an inhibitor of ribonucleotide reductase, 96 mg/m², daily for 4 days every 14 days (one cycle). Eligibility criteria required Eastern Cooperative Oncology Group performance status (ECOG PS) of zero to two with a life expectancy of >3 months; one prior chemotherapy regimen was allowed.Results: Thirty patients were assessable for response and toxicity. Median age was 57 years (range 36–79) and median ECOG PS was one (range 0–2). Thirteen patients had previously been treated with chemotherapy. A total of 130 cycles were administered with a median number of cycles of 3.5 (range 1–8). Mild anaemia (40%), nausea (22%) and fatigue (22%) were commonly reported with G3 and G4 neutropenia documented in 22% and 22%, respectively. Overall response rate was 5.9% (95% confidence interval 0.2% to 28.7%). One patient achieved a partial response, eight had stable disease and 21 progressive disease. Median time to disease progression was 3.9 months.Conclusions: 3-AP Triapine as a single agent, at this dose and schedule, is well tolerated but has only minor activity in the treatment of advanced HNSCC.     

Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck.

PURPOSE: To determine the efficacy and safety profiles of erlotinib in patients with advanced recurrent and/or metastatic squamous cell cancer of the head and neck (HNSCC). PATIENTS AND METHODS: Patients with locally recurrent and/or metastatic HNSCC, regardless of their HER1/EGFR status, were treated with erlotinib at an initial dose of 150 mg daily. Dose reductions or escalations were allowed based on tolerability of erlotinib. RESULTS: One-hundred fifteen patients were enrolled onto this study. Forty-seven percent of patients received erlotinib at 150 mg daily throughout the entire study, 6% had dose escalations, and 46% required dose reductions and/or interruptions. Five patients achieved partial responses on study, for an overall objective response rate of 4.3% (95% CI, 1.4% to 9.9%). Disease stabilization was maintained in 44 patients (38.3%) for a median duration of 16.1 weeks. The median progression-free survival was 9.6 weeks (95% CI, 8.1 to 12.1 weeks), and the median overall survival was 6.0 months (95% CI, 4.8 to 7.0 months). Subgroup analyses revealed a significant difference in overall survival favoring patients who developed at least grade 2 skin rashes versus those who did not (P =.045), whereas no difference was detected based on HER1/EGFR expression. Rash and diarrhea were the most common drug-related toxicities, encountered in 79% and 37% of patients, respectively, though the severity was mild to moderate in most cases. CONCLUSION: Erlotinib was well tolerated in this heavily pretreated HNSCC population and produced prolonged disease stabilization; hence, further evaluation of its role in this tumor type is warranted.     

Somatostatin analogs and prednisone in advanced refractory thymic tumors

BACKGROUND: Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium-labeled octreotide ((111)In-DTPA-D-Phe(1)-octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study. METHODS: Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow-up). In 8 cases, octreotide was replaced by the long-acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated. RESULTS: The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow-up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients). CONCLUSIONS: Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long-acting analog lanreotide, which requires fewer injections, improves patients' compliance.     

A phase 2 study of pemetrexed plus gemcitabine every 2 weeks for patients with recurrent or metastatic head and neck squamous cell cancer

BACKGROUND:

Preclinical studies suggest that additive or synergistic effects are achieved with the combination of pemetrexed plus gemcitabine. A phase 1 study of pemetrexed plus gemcitabine given every 2 weeks demonstrated encouraging preliminary efficacy against head and neck squamous cell cancer (HNSCC).

METHODS:

This was an open‐label, single‐institution, single‐arm, phase 2 study for patients who had received no more than 2 cytotoxic regimens for recurrent and/or metastatic HNSCC. All patients received pemetrexed 500 mg/m² intravenously plus gemcitabine 1250 mg/m² intravenously every 2 weeks with vitamin B12 and folate support. The primary endpoint was the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST); secondary endpoints were to estimate overall survival and to evaluate safety and tolerability.

RESULTS:

Twenty‐five patients received therapy. All patients had received prior radiotherapy, and half had received prior cytotoxic chemotherapy for recurrent and/or metastatic disease. Neutropenia (grade ≥3) occurred in 24% of patients. Four patients (16%) had a partial response (PR) according to RECIST, and 5 additional patients (20%) had objective tumor reductions of >20 but <30% did not meet RECIST criteria for a PR. The median overall survival for all treated patients was 8.8 months.

CONCLUSIONS:

Treatment with pemetrexed plus gemcitabine every 2 weeks with vitamin support generally was well tolerated. The results of this study provided further evidence that pemetrexed may have significant palliative activity against advanced HNSCC. Cancer 2011. © 2010 American Cancer Society.     

Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the efficacy and safety of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Ninety-six eligible patients received cetuximab (initial dose of 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) followed by platinum chemotherapy at the same dose and schedule at which progressive disease was documented before entry onto the study. RESULTS: The response rate, based on an independently read assessment, in the intent-to-treat population was 10%, with a disease control rate (complete response, partial response [PR], and stable disease) of 53%. The median time to progression and overall survival were 85 and 183 days, respectively; both were longest in patients achieving a PR (median, 203.5 and 294 days, respectively). Treatment was well tolerated. The most common cetuximab-related adverse events were skin reactions, particularly an acne-like rash. CONCLUSION: The combination of cetuximab and platinum chemotherapy is an active and well-tolerated approach to the treatment of this poor-prognosis patient population with platinum-refractory recurrent or metastatic SCCHN for whom there are no recommended standard therapeutic options.     

High efficacy of gemcitabine and cisplatin in patients with predominantly anthracycline- and taxane-pretreated metastatic breast cancer

Background: Effective and tolerable regimens are sought specifically in patients who have been pretreated with anthracyclines and taxanes. Gemcitabine and cisplatin demonstrated synergistic activity in vitro and provides a new mechanism of drug interaction. Patients and methods: Previously treated patients with metastatic breast cancer (MBC) were enrolled in a multicentre phase II study. Treatment consisted of gemcitabine (750 mg/m²) and cisplatin (30 mg/m²) given on day 1 and 8 every 3 weeks. Results: Thirty-eight patients were recruited, all of whom had previously received chemotherapy (35 pretreated with taxanes, 33 pretreated with anthracyclines). A median of 5 cycles of the study treatment was delivered. There were 2 complete and 13 partial responses, for an overall response rate of 40% (95% confidence interval: 23–56%). Thirteen patients (35%) had stable disease. Tumour response appeared independent of previously applied chemotherapy. Median time-to-progression was 6 months and median overall survival was 13.5 months. Main toxicities were leucopenia and thrombocytopenia (grade 3/4 in 26 and 16% of cycles, respectively). Non-haematological toxicity was rarely severe. Conclusions: Combination chemotherapy with gemcitabine and cisplatin given on 2 out of 3 weeks is well tolerated and active in heavily pretreated patients with MBC, even after prior exposure to anthracyclines and taxanes. V. Heinemann, H.J. Stemmler contributed equally     

西妥昔单抗联合化疗治疗转移性结直肠癌的临床观察

目的：观察西妥昔单抗联合含伊立替康或奥沙利铂化疗方案治疗转移性结直肠癌的近期疗效及毒副反应。方法：１０例经病理组织学确诊的转移性结直肠癌患者,给予西妥苷单抗联合ＦＯＬＦＩＲＩ方案或ＦＯＬＦＯＸ方案治疗,西妥昔单抗首次给予负荷剂量４００ｍｇ／ｍ^２,每周给予维持剂量为２５０ｍｇ／ｍ^２。结果：全组１０例患者中,完全缓解（ＣＲ）１例,部分缓解（ＰＲ）４例,稳定（ＳＤ）２例,进展（ＰＤ）３例,有效率为５０％,疾病控制率为７０％,中位肿瘤进展时间（ＴＴＰ）为６.４个月。主要毒副反应为痤疮样皮疹和腹泻。结论：西妥昔单抗联合ＦＯＬＦＩＲＩ方案或ＦＯＬＦＯＸ方案治疗转移性结直肠癌疗效较好,毒副反应可耐受。     

长春瑞滨联合顺铂治疗复发或转移性鼻咽癌疗效观察

目的评价长春瑞滨联合顺铂治疗复发或转移性鼻咽癌的疗效及毒性。方法26例复发或转移性鼻咽癌接受长春瑞滨（NVB）25mg／m^2,第1,8天;顺铂（DDP）30mg／m^2,第3,4,5天,21d为一周期,至少化疗2周期。结果总有效率为45．8％,其中CR1例（4．2％）,PR10例（41．7％）,中位无进展生存时间、总生存时间分别为7．8和12．9个月。Ⅲ-Ⅳ度中性粒细胞减少及血小板减少发生率分别为41．6％和38．5％。非血液学毒性轻,可以耐受。结论长春瑞滨联合顺铂治疗复发或转移性鼻咽癌疗效好,毒副反应可以耐受。     

Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC)

PURPOSE: We report four cases of Brain Metastases (BM) from non-small cell lung cancer (NSCLC) responding to ZD 1839 therapy after standard therapy failure. PATIENTS AND METHODS: Four patients with BM from NSCLC, pretreated with two or more lines of chemotherapy, received ZD 1839 (Iressa), on a compassionate use basis, at the daily dose of 250 mg until disease progression. Three patients received Iressa after whole brain radiotherapy (WBRT) failure. RESULTS: After 3 months of ZD 1839 therapy, one patient had complete response on the brain with stabilization of extracranial disease, while the other three patients had partial response both on the brain and on extracranial sites. At the time of this analysis, two patients discontinued the treatment after 5 and 7 months for disease progression, while two patients are still on treatment with no evidence of treatment failure after 3+ and 12+ months. ZD 1839 was generally well tolerated, with skin toxicity recorded in two patients. CONCLUSION: ZD 1839 may be effective in NSCLC patients with pretreated BM. Large and prospective trials need to clarify the role of ZD 1839 in the treatment of BM from NSCLC.