卡培他滨联合顺铂治疗晚期头颈部鳞癌的疗效观察

目的观察卡培他滨联合顺铂方案（XP）治疗晚期头颈部鳞癌的疗效及不良反应,并与5-氟尿嘧啶联合顺铂方案（FP）作随机对照。方法 XP组35例患者：卡培他滨,2500mg/（㎡.d）,分两次口服,餐后30min,第1～14d,顺铂20 mg/㎡,静脉滴注,第1～4d。FP组37例患者：5-FU 750mg/（㎡·d）,CIV9,6h,第1～4d,顺铂20 mg/㎡,静脉滴注,第1～4d。以上方案均为21天重复。结果 XP组和FP组的有效率为57.1%和54.1%（P〉0.05）;中位OS为16.5和15.8月（P〉0.05）。XP组III-IV度粒细胞减少,恶心呕吐,腹泻和口腔炎发生率明显低于FP组。结论 XP和FP均为治疗晚期头颈部鳞癌的较好的化疗方案,XP方案毒副作用小,治疗耐受性好。     

顺铂同步化疗联合尼妥珠单抗用于局部晚期头颈部鳞癌的近期疗效观察

目的：观察顺铂同步化疗联合尼妥珠单抗治疗局部晚期头颈部鳞癌的近期疗效和不良反应。方法：将58例我院初治局部晚期头颈部鳞癌患者根据入院就诊顺序分A、B组（单号为A组,双号为B组）,2组均先行TPF方案（多西紫杉醇75mg·m^-2,d1＋顺铂25mg·m^2,d1-3氟尿嘧啶600mg·m^2,d1-5,每3周重复）诱导化疗2周期,化疗2周期后复查MRI重新分期评估,除鼻咽癌外能手术者行手术治疗,不能手术者行同步化放疗或联合尼妥珠单抗治疗。A组：行放疗同步每周予顺铂化疗（静脉滴注30mg·m^-2,每周1次,共用6次）;B组：在A组的基础上予尼妥珠单抗（放疗前1周静脉滴注200mg,放疗同时静脉滴注100mg,每周1次,共用7次）。治疗结束后评价2组近期疗效和不良反应。结果：中位随访时间为13个月。A、B组的诱导化疗有效率分别为69．0％和79．3％（P=0．368）。A组近期有效率为89．7％,1年生存率为89．7％;B组近期有效率为93．1％,1年生存率为96．6％,B组近期有效率和1年生存率均优于A组,但2组比较差异无统计学意义（P〉0．05）。2组主要不良反应为血液学毒性和口腔黏膜炎,发生情况相似,均未观察到超敏反应发生。结论：诱导化疗后同步化放疗联合尼妥珠单抗治疗局部晚期头颈部鳞癌近期疗效确切,患者耐受性较好,不良反应并未因尼妥珠单抗的联合使用而增加,远期疗效尚待观察。     

Survivin在头颈部肿瘤中研究进展

Survivin是一种IAP家族蛋白,具有抗细胞凋亡的功能,并且参与细胞有丝分裂的调节和胞质分裂。Survivin在头颈部肿瘤如口腔SCC、口咽SCC、喉SCC肿瘤组织中明显升高,并且与头颈部恶性肿瘤的恶性程度与生存率明显相关。联合Survinvin抑制剂、化学治疗、放射性治疗等能够增加对头颈部恶性肿瘤的治疗效果。     

脱氢环氧甲基醌霉素对头颈鳞癌细胞侵袭的抑制

目的:研究核因子kappaB(NF-κB)抑制剂—脱氢环氧甲基醌霉素(DHMEQ)对头颈鳞癌细胞(HNSCC)侵袭的抑制作用。方法:以鼻咽鳞癌细胞株YCU-N861和下咽鳞癌细胞株YCU-H891为研究对象,应用westernblot法检测经不同浓度DHMEQ处理后细胞中基质金属蛋白酶9(MMP-9)的表达水平;应用invasion chamber试剂盒检测DHMEQ对细胞侵袭力的影响。结果:随DHMEQ用药浓度的增加,细胞中MMP-9蛋白的表达呈下降趋势,细胞侵袭能力受抑制。结论:通过抑制NF-κB,DHMEQ可抑制头颈鳞癌细胞的侵袭。     

A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer

In a previous phase II trial of thesynthetic topoisomerase I inhibitor,9-aminocamptothecin (9-AC), given as a72-h infusion, we identified modestsingle agent activity of 9% in patientswith previously untreated advancednon-small cell lung cancer (NSCLC).Preclinical studies suggested that a moreprolonged continuous infusion of the drugmight lead to greater antitumor activity. Aphase I study recommended a phase II doseof 25 g/m²/hr for 120 h(3000 g/m² over 5 days),administered for 2 consecutive weeks of a3-week cycle. We utilized this schedule andenrolled 13 chemotherapy-nave patientswith Stage IIIB and IV NSCLC in this trial:median age 67 (range 57–74); 46% male;92% stage IV; and median performancestatus 1. Twelve patients are availablefor response and toxicity evaluation after2 cycles of therapy. One patient achieveda partial response. Four patients hadstable disease while seven patients hadprogressive disease. Patients with stableor progressive disease after two cyclesreceived no additional 9-AC, and wereoffered conventional chemotherapy. Themedian survival time was 10.2 months andthe one-year survival rate 28% (95%confidence interval, 5–58%). Significant toxicities includedmyelosuppression, fatigue, and anorexia. One patient had grade 4 neutropeniafollowing the first week of cycle 2, anddid not receive additional therapy. Therewere no neutropenia-related infections.These data suggest that this prolongedschedule is unlikely to increase 9-AC'svery modest activity in NSCLC above thatseen with the simpler 72-hadministration schedule. Furtherevaluation of 9-AC in NSCLC is notrecommended.     

Phase II study of amonafide in the treatment of patients with advanced squamous cell carcinoma of the head and the neck

Summary Amonafide (nafidimide), a synthetic organic compound with an inhibitory effect on cellular replication, was used in a phase II study conducted by the Illinois Cancer Center in order to assess its efficacy and toxicity in advanced or recurrent squamous cell cancer of the head and neck. Eligible patients had received no more than one prior adjuvant or neoadjuvant chemotherapy, had normal bone marrow, renal and hepatic function, ECOG performance status of 0–2, and bidimensionally measurable disease. Eligible patients were administered amonafide at a starting dose of 300 mg/m² for five consecutive days every 3 weeks with dose escalation or de-escalation according to established hematologic criteria in the absence of disease progression. Nineteen of 22 entered patients were evaluable for response and all patients were evaluable for toxicity. Eleven of 19 patients achieved stable disease. Median time to progression after start of treatment was 57 days, for the 18 patients for whom the date of progression is known. There were no partial or complete responses. Hematologic toxicity was dose limiting with grade 3–4 neutropenia in 50 percent of patients and 4 deaths associated with neutropenic sepsis. Non-hematologic toxicity was mild to moderate with nausea and vomiting predominating. In this study, amonafide was a myelotoxic, inactive treatment in advanced/ recurrent head and neck cancer. Further use in head and neck cancer appears unwarranted.     

局部晚期头颈部鳞癌患者血清肿瘤标志物水平对尼妥珠单抗近期疗效及预后的预测价值

目的 探讨血清肿瘤标志物水平变化对局部晚期头颈部鳞癌患者尼妥珠单抗近期疗效及预后的预测价值。方法 回顾性分析160例接受尼妥珠单抗治疗的局部晚期头颈部鳞癌患者的临床资料,包括治疗后4周的RECIST 1.1疗效评价、无疾病进展生存期（progression-free survival,PFS）以及治疗前和疗效评价时的胸苷激酶1（thymidine kinase 1,TK1）、细胞角蛋白19片段（cytokeratin-19-fragment antigen 21-1,CYFRA21-1）和人鳞状细胞癌相关抗原（squamous-cell carcinoma-related antigen,SCC-Ag）水平。结果 160例局部晚期头颈部鳞癌患者治疗有效率[完全缓解（complete response,CR）+部分缓解（partial response,PR）]为33.13%（53/160）,靶向治疗前CR+PR患者血清TK1、CYFRA21-1高于疾病稳定（stable disease,SD）、疾病进展（progressive disease,PD）患者（P<0.05）,SCC-Ag基线水平低于SD、PD患者;靶向治疗后CR+PR患者TK1、CYFRA21-1水平降低,PD患者TK1、CYFRA21-1水平升高,SD患者TK1水平降低（P<0.05）。受试者工作特征（receiver operating characteristic,ROC）曲线显示TK1、CYFRA21-1、SCC-Ag变化率与影像学评效一致性的最佳截断点分别为0.265,0.357,0.393,曲线下面积分别为0.774,0.683,0.660。Kaplan-Meier生存分析显示TK1较治疗前升高≤26.5%的患者PFS长于升高>26.5%的患者[22.524个月vs 18.793个月,P=0.002],CYFRA21-1较治疗前升高≤35.7%的患者中位PFS长于升高>35.7%的患者[22.381个月vs 20.130个月,P=0.030],SCC-Ag较治疗前升高≤39.3%与升高>39.3%的患者中位PFS比较无显著差异[20.773个月vs 18.947个月,P=0.078]。结论 TK1、CYFRA21-1、SCC-Ag水平对局部晚期头颈部鳞癌患者尼妥珠单抗治疗的近期疗效和预后有重要的预测价值。     

头颈部鳞状细胞癌靶向治疗的研究进展

靶向治疗是目前治疗头颈部鳞状细胞癌的研究热点。许多新型的药物制剂治疗方案都在进行临床试验的评估。治疗头颈部鳞状细胞癌的靶向治疗制剂主要有涉及EGFR信号通路的单克隆抗体,如西妥昔单抗;EGFR-TKI,VEGF抑制剂、NF-kB信号通路的阻断剂、IGFR抑制剂和p53信号通路的载体。     

Phase II trial of N-methylformamide in advanced head and neck cancer

Summary Eighteen patients with advanced epidermoid carcinoma of the head and neck were entered into a phase II trial of N-Methylformamide (NMF), 800 mg/M² IV daily for 5 days every 4 weeks. Seventeen patients had received prior radiation therapy and 11 were previously treated with chemotherapy. No complete or partial responses were observed. The major toxicity was gastrointestinal. Fifty percent of patients experienced nausea and vomiting or reversible hepatotoxicity with greater than a 3-fold elevation of liver enzymes. Mild reversible myelosuppression occurred in 2 patients. NMF in this dose and schedule was not a useful agent to treat recurrent epidermoid carcinoma of the head and neck.     

替吉奥胶囊治疗老年晚期头颈部肿瘤21例疗效观察

目的:探讨替吉奥胶囊治疗老年晚期头颈部肿瘤的临床疗效和相关不良反应.方法:分析用替吉奥胶囊治疗老年晚期头颈部肿瘤21例的临床资料.结果:21例患者均服药2个疗程以上,有效率达57%,生活质量明显改善,15例生存时间＞12个月(71%).主要不良反应是骨髓抑制和消化道反应,但无Ⅳ度不良反应,且停药后这些指标均能回归到正常...     

9-Aminocamptothecin (9-AC) given as a 120-hour continuous infusion in patients with advanced adenocarcinomas of the stomach and gastroesophageal junction: A phase II trial of the University of Chicago phase II consortium

9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin derivative that demonstrated broad activity in pre-clinical studies. In vitro, greater anti-tumor efficacy can be achieved with prolonged administration. A minor response was observed in gastric cancer in a phase I study. We conducted a phase II study of 9-AC in 15 patients with previously untreated metastatic gastric cancer and adenocarcinoma of the gastroesophageal junction. 9-AC was administered at a dose of 25 microg/m(2)/h over 120 hours (3000 microg/m(2) over 5 days) on two consecutive weeks every 21 days. Fourteen patients were evaluable for response. There were no objective responses. Three patients had stable disease lasting a median of 3.4 months (range 1.6-4.3 months). Median time to progression was 1.4 months; median survival was 5.2 months. Grade 3 neutropenia developed in 20% of patients, and anemia in 7%. Grade 3 nausea and fatigue each developed in 7% of patients. We conclude that 9-AC given by 120-hour continuous infusion demonstrates no clinical activity in patients with metastatic gastric cancer.     

Phase II evaluation of menogaril in patients with advanced cervical carcinoma

Fourteen patients with advanced/recurrent squamous cell carcinoma of the uterine cervix received menogaril, 200 mg/m² by one hour intravenous infusion at four-week intervals. No objective regressions were observed. Median time to progression was less than two months and median survival was seven months. All patients experienced neutropenia. Platelet toxicity was negligible. Venous irritation and phlebitis occurred at the infusion site in 43% of patients. Menogaril as administered in this protocol is ineffective in treating previously irradiated advanced/recurrent squamous cell carcinoma of the uterine cervix and warrants no further investigation in this disease at the dosage and administration schedule used in this protocol. Address for offprints: H.J. Long, Mayo Clinic, 200 First Street S.W., Rochester, MN, 55905, USA     

Phase II trial of 9-aminocamptothecin (NSC 603071) administered as a 120-hour continuous infusion weekly for three weeks in metastatic colorectal carcinoma

9-Aminocamptothecin (9-AC) is a camptothecin derivative with broad antitumor activity in preclinical studies. Prior investigations suggested that prolonged maintenance of 9-AC lactone plasma concentrations above 10 nmol/l and frequent administration of the drug are important determinants of antitumor activity. Our phase II study, therefore, examined a 5-day continuous infusion of 9-AC weekly for 3 weeks in patients with advanced colorectal cancer. Eighteen patients previously untreated for metastatic disease received 480 g/m²/day of 9-AC. No responses were observed in 17 evaluable patients. Severe toxicities included granulocytopenia, nausea, vomiting and diarrhea. The median absolute granulocyte count (AGC) nadir was 2,300/l (range 0–9,000/l) and occurred on day 10. Eight patients received an escalated dose of 600 g/m²/day. The median AGC nadir at the escalated dose was 1,500/l (range: 300–2,700/l) and occurred on day 22. The median number of courses given was 2 (range: 1–8); and the median time to disease progression was 8 weeks (range: 1–40 weeks). 9-AC administered by this schedule lacked antitumor activity in patients with advanced colorectal carcinomas.     

A Phase I Trial of Cisplatin Plus Decitabine, a New DNA-Hypomethylating Agent, in Patients with Advanced Solid Tumors and a Follow-Up Early Phase II Evaluation in Patients with Inoperable Non-Small Cell Lung Cancer

The authors describe a phase I trial of cisplatin plusdecitabine, a novel DNA-hypomethylating agent, in patients withadvanced solid tumors, which was followed by an early phase IIevaluation of the combination in patients with inoperablenon-small cell lung cancer (NSCLC). In the phase I trial,cisplatin was studied at a fixed dose of 33 mg/m²,while decitabine was escalated in four (I–IV) doseescalation levels (45, 67, 90 to 120 mg/m²,respectively) in consecutive groups of at least 3 patients perdose level. Decitabine was administered to the patients as atwo-hour intravenous infusion, while cisplatin was givenintravenously immediately after the end of decitabine infusion.Both agents were given on days 1–3 every 21 days.Twenty-one patients were included in the phase trial. Dose levelIV (120 mg/m² decitabine) was considered the maximumtolerated dose (MTD), while the dose-limiting toxicities wereneutropenia, thrombocytopenia and mucositis. The recommendeddoses for phase II trials in good- and poor-risk patients were90 (level III) and 67 mg/m² (level II), respectively.One short-lasting partial response was observed in a patient withcervical cancer, while two minor regression were documented ina patients with NSCLC and cervical cancer, respectively. Doselevel II was selected for the phase II trial in patients withinoperable NSCLC. Fourteen consecutive patients were included inthis part of the study. The median age of the patients was 57years (range, 39–75), male/female ratio of –11/3 anda median WHO performance status 1 (0–2). The stage ofdisease were IIIB (5) and IV (9). Prior irradiation to the chestwas given in one case. A total of 30 treatment courses wereevaluable for toxicity and response, with a median of 2 coursesper patient (1–4). Grade 3–4 neutropenia andthrombocytopenia were observed in about half of the cases.Mucositis, diarrhea, nausea and vomiting, and skin rash were alsoobserved in some patients. Three minor responses were documented,which lasted for 4, 16 and 36 weeks. Median survival of patientswas 15 weeks (4–38). In conclusion, the cisplatin plusdecitabine combination did not exhibit significant antitumoractivity in patients with NSCLC at the dose and schedule appliedin this trial to justify its further evaluation in this patientpopulation.     

Phase II Trial of Temozolomide in Patients with Cisplatin-Refractory Germ Cell Tumors

Fourteen patients with cisplatin-refractory germ cell tumors (GCT) were treated with temozolomide on a phase II trial. Temozolomide was given orally at 150 mg/m2/day on days 1-5. The cycle length was 28 days. No patient experienced a grade 3 or 4 toxicity, and none of the 14 evaluable patients achieved a complete or partial response. Temozolomide is not efficacious in the treatment of cisplatin-refractory GCT patients.     

Phase II Trial of Pyrazoloacridine as Second-Line Therapy for Patients with Unresectable or Metastatic Transitional Cell Carcinoma

Purpose: A phase II trial of pyrazoloacridine(PZA) was conducted to assess its activity andtoxicity in patients with advanced transitional cellcarcinoma (TCC) refractory to or progressing after oneprior cisplatin-, carboplatin- or paclitaxel- basedregimen. Patients and methods: PZA at a dose of750 mg/m² was administered to 14 patients as athree-hour intravenous infusion on day 1 every 21days. Premedication consisted of lorazepam 0.5-1.0 mgprior to each cycle to alleviate central nervoussystem toxicity. Reduction of subsequent doses wasmade for hematologic or central nervous systemtoxicity. Results: Among fourteen patients evaluable forresponse, no responses were observed (0% responserate; 95% confidence interval 0% to 23%). Themedian duration of survival for all patients was 9months with a median follow-up of 8.5 months. Toxicityto PZA included grade 3 or 4 neutropenia in 8/14(57%) and grade 3 or 4 thrombocytopenia in 2/14(14%). Non-hematologic toxicity was mild. Conclusions: PZA at this dose and schedule does nothave significant single-agent acitvity in patientswith TCC who have failed one prior regimen.     

Treatment of advanced squamous cell carcinoma of the head and neck with isotretinoin: a phase II randomized trial

Summary Retinoids, the analogs of vitamin A, are active in vitro and in vivo against squamous cell carcinoma in animals and against certain epithelial precancers and cancers in humans. These data led us to design a prospective, multi-institutional, randomized phase II trial of isotretinoin in advanced head and neck squamous cell carcinoma. We randomly assigned 40 patients to receive isotretinoin or methotrexate, the best-studied and most active single agent for this disease. Overall, the study patients had extremely poor prognoses, i.e., low performance statuses and recurring disease after surgery and/or irradiation. Three objective responses (16%), including one complete response, occurred in the 19 evaluable isotretinoin-treated patients. Only one minor response (5%) occurred in the methotrexate-treated group. Toxicity occurred with both drugs, but was manageable and never life threatening in the retinoid group. These results and the established activity of retinoids in oral leukoplakia (a precursor of head and neck cancer) indicate the need for further study of this class of drugs in head and neck cancer.     

A Phase II trial of 6-Hydroxymethylacylfulvene (MGI-114, Irofulven) in Patients with Advanced Non-Small Cell Cancer Previously Treated with Chemotherapy

Purpose: To test the efficacy and safety ofthe novel antitumor agent MGI-114 (NSC 683863) in patientswith advanced non-small cell lung cancer (NSCLC) previouslytreated with chemotherapy. Methods: A two-stageaccrual design was used to ensure detection of a true responserate of at least 20% with a type I error of .04.Eligible patients received 11 mg/m² daily for fiveconsecutive days. Cycles were repeated every 28 days.Results: Fifteen patients received a total of 34cycles of MGI-114. All patients had a performance status of 0or 1. Eleven patients had previously received carboplatin andpaclitaxel +/– radiation. Two patients had receivedcisplatin and CPT-11, one patient had received weeklypaclitaxel, and one patient had received carboplatin anddocetaxel. None of the first 15 patients enrolled experiencedobjective tumor response, and the study was closed. Fortypercent of patients developed grade 2 thrombocytopenia.Grade 3 nausea and grade 2 vomiting were observed in40% and 47% of patients respectively.Thirty-three percent of patients experienced grade 2fatigue. Conclusions: MGI-114, at this dose andschedule, does not have significant activity as second linetherapy for patients with advanced NSCLC.     

A Clinical Screening Cooperative Group phase II evaluation of lobaplatin (ASTA D-19466) in advanced head and neck cancer

Summary We evaluated the efficacy and tolerability of lobaplatin, a new platinum compound, given at the dose of 50 mg/m² by i.v. bolus every 4 weeks, in 49 patients with advanced and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). One complete and 2 partial responses were observed in 43 eligible patients for an overall response rate of 7% (95% confidence interval: 1–19%). The duration of responses was 11, 16 and 32 weeks. Toxicities of WHO grade 3 were hematologic: thrombocytopenia in 26%, granulocytopenia in 12% and anemia in 12% of patients. There was no therapy-related death. Nausea/vomiting, diarrhoea and paresthesia were mild and rare. In conclusion, lobaplatin was well tolerated, but its efficacy in advanced SCCHN at the presented dose and schedule, was marginal.