Gemcitabine and cisplatin in advanced nasopharyngeal carcinoma: a pilot study

A pilot study was performed to evaluate the efficacy and safety of gemcitabine and cisplatin combination in the treatment of patients with metastatic nasopharyngeal carcinoma (NPC). Eligible patients were those with metastatic NPC who had been treated with radiotherapy and cisplatin plus 5-fluorouracil chemotherapy. Cisplatin was given intravenously at the fixed dose of 30 mg/m² on days 1-3. Gemcitabine was intravenously administered over 30 min infusion with the dose escalated from 800 to 1200 mg/m² on days 1 and 8. The 3-week schedule defined a cycle of treatment. Fifteen patients were enrolled and assessed for the worst toxicities. For a total of 83 cycles, Grade 3-4 toxicity was 46.7% for neutropenia, 40.0% for thrombocytopenia, and 20.0% for anemia. Grade 3 nonhematologic toxicity was 13.3%. Fourteen patients were assessable for response. The overall response rate was 92.9%, with complete response in three patients (21.4%). Median survival was 10.2 months. Seven patients had lived more than one year, and two patients had lived more than 2 years. The recommended dose of gemcitabine was 1000 mg/m² on days 1 and 8 in each cycle. In conclusion, the present combination is well tolerated and highly active in the treatment of advanced NPC patients.     

Gemcitabine combined with docetaxel for the treatment of unresectable pancreatic carcinoma

Purpose. To assess the efficacy and toxicity of combination therapy with gemcitabine and docetaxel in patients with unresectable pancreatic carcinoma. Patients and Methods. Thirty-four patients with unresectable stage III, IVA, and IVB pancreatic carcinoma were eligible for this study. The first 18 patients received gemcitabine 800 mg/m² intravenously (IV) on days 1, 8, and 15 and docetaxel 75 mg/m² IV on day 1, repeated every 28 days. Due to a high incidence of myelosuppression in this first group, the treatment schedule was modified in the remaining patients to gemcitabine 1,000 mg/m² IV and docetaxel 40 mg/m² IV on days 1 and 8 of a 21-day schedule. The primary study endpoints were objective response rate and duration of survival. Results. Ten of 33 evaluable patients achieved a partial response, for an overall response rate of 30.3% (95% CI, 16.21%-48.87%). Partial responses noted in the pancreas and a variety of metastatic sites were maintained for 4 to 12 months (median 6 months). Twelve additional patients (36%) experienced stable disease. The median time to progression was 6 months, and median survival was 10.5 months. The toxicity profile of the modified gemcitabine/docetaxel schedule was more favorable than that associated with the initial regimen, particularly with respect to hematologic toxicity. Conclusion. The response and survival data reported here for combination therapy with gemcitabine and docetaxel are encouraging given the poor prognosis associated with unresectable pancreatic cancer. These data suggest that gemcitabine plus docetaxel may be more effective than either agent alone in the treatment of pancreatic cancer and warrants further study.     

Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study.

BACKGROUND: To evaluate the efficacy and toxicity of combination gemcitabine plus cisplatin (GC) chemotherapy in metastatic or recurrent nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Forty-four patients of Chinese ethnicity with metastatic or recurrent NPC received ambulatory GC chemotherapy every 28 days (gemcitabine 1000 mg/m(2) days 1, 8 and 15; cisplatin 50 mg/m(2) days 1 and 8). There were 40 male and four female patients with a mean age of 47.4 years. More than half (54.5%) of the patients had received either prior platinum-based chemotherapy and/or radiotherapy to target lesions. RESULTS: There were nine complete responses and 23 partial responses in the 44 patients, achieving an overall response rate of 73% (78% for the 41 assessable patients). The mean duration of response was 5.3 months. Improved subjective symptom-control scores were found in 78% of patients with pre-existing symptoms, while 64% of patients experienced improved general well-being scores. Toxicity was mainly hematological: grade III/IV anemia, granulocytopenia and thrombocytopenia were found in 11, 37 and 16% of cycles, respectively. With a median follow-up of 17.2 months, 62% survived 1 year while 36% were alive and progression free. CONCLUSIONS: Gemcitabine plus cisplatin chemotherapy offers a satisfactory overall response rate, subjective patient improvement and safety profile for metastatic and recurrent NPC.     

Biweekly low-dose sequential gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (GFP): a highly active novel therapy for metastatic adenocarcinoma of the exocrine pancreas

Phase II studies have suggested an improved response rate and acceptable toxicity profile associated with gemcitabine combinations compared to gemcitabine alone for treatment of metastatic adenocarcinoma of the pancreas. The GFP regimen (gemcitabine, 5-fluorouracil, leucovorin, and cisplatin) is based on laboratory evidence of disease-specific chemotherapy interaction.[8] This retrospective analysis examined the outcome of 49 consecutive patients with histologically confirmed metastatic pancreatic adenocarcinoma treated between July 1998 and September 2000. Day 1 treatment consisted of gemcitabine 500 mg/m² over 30 minutes and then leucovorin 300 mg bolus, 5-fluorouracil (5-FU) 400 mg/m² bolus, followed by infusional 5-FU 600 mg/m² over 8 hours. Day 2 consisted of leucovorin 300 mg bolus, 5-FU 400 mg/m² bolus, followed by cisplatin 50-75 mg/m² over 30 minutes and then infusional 5-FU 600 mg/m² over 8 hours. Treatment was administered every 2 weeks. Median patient age was 61.5 years, 74% were men, and 20 patients had refractory disease (11 patients had disease progression upon gemcitabine-based therapy). Grade 3-4 toxic effects (% patients) consisted of neutropenia (30%), thrombocytopenia (14%), anemia (8%), and neutropenic fever (2%). Grade 3-4 nonhematological toxicities (% patients) consisted of neuropathy (14%), ototoxicity (8%), nephrotoxicity (6%), nausea/vomiting (14%), and mucositis (10%). The majority of dose reductions were made for neuropathy or cytopenias. Filgrastim and erythropoietin were given as needed to promote dose intensity. Eight patients attained a partial response (PR) by RECIST criteria. Fourteen had stable disease (SD). Two patients attaining PR and two attaining SD had progressive disease with prior gemcitabine-based therapy. The median time to disease progression (TTP) from GFP start was 9 weeks. For all 49 patients, the median overall survival (OS) from GFP start was 10.6 months, 12-month survival was 46%, and 24-month survival was 30%. Notably, upon disease progression, 31 patients continued to receive the GFP regimen with irinotecan 80 mg/m² inserted on day 1 following gemcitabine, the G-FLIP regimen (gemcitabine, 5-fluorouracil, leucovorin, irinotecan, and cisplatin). Measured from G-FLIP initiation, the TTP for the 31 patients treated sequentially was 10 weeks, and for the 14 patients attaining SD or PR the TTP was 25 weeks. The median overall survival measured from GFP initiation was 11.8 months. The response rate, non-cross resistance, TTP, OS, and tolerability warrant prospective development of this novel combination. This experience also demonstrates that adding a single new drug such as irinotecan to the same first-line chemotherapy combination upon disease progression may be an important alternative for the treatment of relapsed/resistant cancer.     

GP、PF及TPF方案化疗联合调强适形放疗治疗鼻咽癌的临床疗效

背景与目的：诱导化疗联合放疗及辅助化疗治疗鼻咽癌的疗效目前尚未明确,本研究旨在比较GP（吉西他滨+顺铂）方案、PF（顺铂+氟尿嘧啶）方案及TPF（多西他赛+顺铂+氟尿嘧啶）方案化疗联合调强适形放疗（intensity-modulated radiotherapy,IMRT）在无远处转移鼻咽癌患者中的临床疗效。方法：本研究回顾性分析了2009年1月—2010年12月期间在复旦大学附属肿瘤医院放疗科接受诱导化疗联合IMRT及辅助化疗的134例无远处转移鼻咽癌患者。GP组（吉西他滨1 000 mg/m2,第1、8天+顺铂25 mg/m²,第1~3天）、PF组（顺铂25 mg/m²,第1~3天+氟尿嘧啶500 mg/m²,第1~5天,持续静脉滴注）及TPF组（多西他赛75 mg/m²,第1天+顺铂25 mg/m²,第1~3天+氟尿嘧啶500 mg/m²,第1~5天,持续静脉滴注）分别纳入55、20和59例患者。诱导化疗每21 d重复,2~3个疗程后行IMRT。原发灶及阳性淋巴结的大体肿瘤靶区（gross tumor volume,GTV）的处方剂量分别为（66.0~70.4）Gy/（30~32）次和66.0 Gy/（30~32）次。放疗结束28 d后行辅助化疗2~3个疗程,方案与之前接受的诱导化疗方案相同。随访并比较3组不同的诱导化疗联合放疗及辅助化疗方案的患者5年总生存期（overall survival,OS）、无病生存期（disease-free survival,DFS）及局部无复发生存期（local recurrence-free survival, LRFS）情况。结果：GP组、PF组和TPF组的5年OS率分别为91.9%、75.1%和90.8%,5年LRFS率分别为95.8%、82.3%和96%。GP组的5年OS率（P=0.041）高于PF组,TPF组的5年LRFS率高于PF组（P=0.043）。TPF组和GP组间生存曲线差异无统计学意义。结论：GP方案诱导化疗联合IMRT及辅助化疗治疗无远处转移鼻咽癌的临床疗效可能优于PF方案,尚待大样本数据验证。三药联合的TPF方案并未优于GP方案。可考虑展开Ⅲ期临床试验评价GP方案诱导化疗在无远处转移初治鼻咽癌人群中的疗效。     

A phase II trial of sequential chemotherapy with docetaxel and methotrexate followed by gemcitabine and cisplatin for metastatic urothelial cancer

Administration of noncross-resistant agents in a sequential fashion may improve outcome by targeting tumor cells with different sensitivity profiles. We evaluated the toxicity and response rate of docetaxel and methotrexate (DM) followed by gemcitabine and cisplatin (GC) in patients with metastatic or unresectable transitional cell carcinoma of the urothelium. Patients received 3 cycles of DM (40 mg/m2 methotrexate on days 1 and 8 and 100 mg/m2 docetaxel on day 8 repeated every 21 days) followed by GC (1000 mg/m2 gemcitabine on days 1 and 8 and 75 mg/m2 cisplatin on day 1 repeated every 21 days). The most common toxicities were hematologic, with grade 3/4 neutropenia and thrombocytopenia observed in 4 and 2 patients, respectively. Four partial responses were observed after DM (4 of 12, 33% response rate) and 6 responses (3 partial response, 3 complete response, 6 of 9, 67% response rate) after GC for an overall response rate of 7 of 13 (54%). Three patients who progressed on DM responded to GC and 3 responders to DM achieved further response to GC. The median overall survival was 13.6 months. Although we do not recommend this particular sequence of chemotherapy for further study, the uncompromised median survival and the ability to salvage responses with GC suggest that testing of novel agents in sequence with GC is a feasible strategy.     

Phase II study of cisplatin, epirubicin, UFT, and leucovorin (PELUF) as first-line chemotherapy in metastatic gastric cancer

More than two-thirds of patients with gastric cancer present with metastatic disease and their curative options are limited. This phase II study assessed the efficacy and tolerability of cisplatin, epirubicin, tegafur-uracil (UFT) and leucovorin in patients with metastatic gastric cancer (MGC). Thirty-nine patients with previously untreated metastatic or unresectable gastric cancer received intravenous cisplatin 60 mg/m² and epirubicin 50 mg/m² on day 1 of a 28-day cycle; UFT 300 mg/m² was administered with oral leucovorin 30 mg/day in divided doses on days 1-22, followed by a 7-day rest. Two patients achieved a complete response, 13 had a partial response (overall response rate 38%; 95% confidence interval [CI] 24-52%) and 16 patients (41%) had stable disease. Median time to progression was 6.5 months (95% CI 5.5-7.5 months); overall survival was 9.5 months (95% CI 8.5-13.5 months). Grade 3/4 neutropenia, anemia, and thrombocytopenia occurred in 20%, 8%, and 3% of patients, respectively; two patients experienced febrile neutropenia. Grade 3 diarrhea occurred in three patients. The combination of cisplatin, epirubicin, UFT, and leucovorin has significant activity and tolerable toxicities in patients with MGC and represents a convenient treatment option for these patients.     

多西他赛联合吉西他滨治疗复发转移性乳腺癌临床疗效及预后影响因素

目的 探讨多西他赛联合吉西他滨治疗复发转移性乳腺癌的临床疗效及预后影响因素.方法 复发转移性乳腺癌患者46例,给予多西他赛联合吉西他滨治疗,具体方案为:多西他赛75 mg/m2,静脉滴注1h,第1天;吉西他滨1000 mg/m2,静脉滴注30 min,第1、8天;21 d为1个周期,评价患者近期疗效并随访患者总生存时间和无进展生存时间.采用单因素x2检验和多因素Cox风险比例模型分析患者临床病理特征与总有效率和总生存时间的关系.结果 46例复发转移性乳腺癌患者均接受3～6个周期的联合化疗治疗,完全缓解4例(8.7％),部分缓解22例(47.8％),稳定12例(26.1％),进展8例(17.4％),总有效率为56.5％ (26/46),疾病控制率为82.6％ (38/46);中位总生存时间为16.0个月(95％ CI为6.5 ～25.5个月),中位无进展生存时间为8.0个月(95％ CI为6.2～9.8个月);单因素分析结果显示,患者年龄、绝经状态、行为状况(PS)评分、肿瘤转移数目均与患者总有效率相关(P＜0.05),多因素Cox风险比例模型分析显示,患者年龄、绝经状态、PS评分、肿瘤转移数目均与患者的总生存时间相关,是患者预后的影响因素(P＜0.05);主要不良反应以骨髓抑制、胃肠道反应、皮疹、脱发及乏力为主,大多数为Ⅰ～Ⅱ级.结论 多西他赛联合吉西他滨治疗复发转移性乳腺癌的临床疗效好,安全性高;患者年龄、绝经状态、PS评分、肿瘤转移数目可作为该方案预后的影响因素.     

Taxanes as first-line therapy for advanced non-small cell lung cancer: a systematic review and practice guideline

This evidence-based practice guideline on the use of paclitaxel (Taxol^®) or docetaxel (Taxotere^®) as first-line treatment for patients with advanced non-small cell lung cancer who are candidates for palliative first-line chemotherapy is based on a systematic search and review of literature published in full or in abstract form between 1985 and April 2005. Forty-five randomized trials, including 11 abstracts, were reviewed and clinicians in the province of Ontario, Canada, provided feedback on a draft version of the guideline. Two phase III trials detected a statistically significant survival advantage for a taxane (paclitaxel or docetaxel) with best supportive care versus best supportive care alone. Among the nine fully published phase III trials comparing platinum-based chemotherapies, taxane-platinum combinations achieved higher response rates compared with older chemotherapy combinations, although significantly longer survival was observed only for docetaxel-cisplatin compared with vindesine-cisplatin. Response rates and survival were generally not significantly different for taxane-platinum combinations compared with other current chemotherapy combinations, although the toxicity profile of the regimens varied. However, in one large trial, improved tumor response and modest survival and quality of life benefits were associated with docetaxel-cisplatin compared with vinorelbine-cisplatin. No statistically significant survival differences were detected in the three fully published phase III trials comparing a taxane-gemcitabine combination with a taxane-platinum regimen.

Recommendations: (i) paclitaxel or docetaxel combined with cisplatin is recommended as one of a number of chemotherapy options for the first-line treatment of advanced non-small cell lung cancer in patients with a good performance status; (ii) carboplatin may be combined with a taxane if a patient is unable or unwilling to take cisplatin; (iii) a taxane-gemcitabine combination may be considered for patients with a contraindication to cisplatin and carboplatin; (iv) no firm recommendation can be made on the optimal dose and schedule of taxane-based chemotherapy; however, commonly used regimens include cisplatin 75 mg/m² combined with either docetaxel 75 mg/m² or paclitaxel 135 mg/m² (24-h infusion) and carboplatin AUC 6 combined with paclitaxel 225 mg/m² (3-h infusion); (v) a single-agent taxane may be used if combination chemotherapy is considered inappropriate.     

A Phase II trial of docetaxel and cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma

A Phase II study was conducted to determine the efficacy and toxicity of the combination of docetaxel and cisplatin, in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC). Nine patients (median age 39 years) with NPC were enrolled, none had prior chemotherapy for their recurrent or metastatic disease. Docetaxel was administered as a 1-h intravenous infusion at a dose of 75 mg/m(2) on day 1; cisplatin was administered at a dose of 75 mg/m(2) on day 1, immediately after docetaxel. Treatment was repeated every 3 weeks. The primary endpoint was objective response rate and the secondary endpoints were duration of response, time to progression, and overall survival. A total of 45 chemotherapy cycles were administered. In an intention-to-treat analysis two patients (22%, 95% confidence interval (CI): 3-60%) achieved a partial response. The median duration of response was 4.1 months, the median time to progression 8.4 months and the overall survival at 1 year from start of treatment was 76%. Grade 3-4 neutropenia was observed in all (100%) patients over 93% of the treatment cycles, and in three cases this was complicated by fever. Other toxicities were mild. CONCLUSIONS: The combination of docetaxel and cisplatin has manageable toxicity but little efficacy as first-line treatment in patients with recurrent or metastatic NPC. In view of the low response rate, accrual was terminated and the trial was aborted.     

Paclitaxel, carboplatin, and gemcitabine in metastatic nasopharyngeal carcinoma: a Phase II trial using a triplet combination

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) are treated primarily with radiotherapy. In the disseminated state, platinum-based, 2-drug combination regimens yielded response rates of 55-75%, achieving a median survival of 10-12 months. With the proven efficacy of second-generation cytotoxics like paclitaxel and gemcitabine in patients with metastatic NPC, the authors hypothesized that a triplet combination incorporating these newer cytotoxics may improve treatment results. METHODS: Thirty-two patients with metastatic NPC were treated with combination chemotherapy that included paclitaxel 70 mg/m(2) on Days 1 and 8, carboplatin dosed to area under curve of 5 on Day 1, and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days for a maximum of 8 cycles. RESULTS: Two patients achieved a complete response, and 23 patients achieved a partial response, for an overall response rate of 78%. The main toxicities were hematologic, with 41% of patients experiencing Grade 3 or 4 anemia, 41% of patients experiencing Grade 3 or 4 thrombocytopenia, and 78% of patients experiencing Grade 3 or 4 neutropenia. The median time to disease progression was 8.1 months, and the median overall survival was 18.6 months. CONCLUSIONS: The combination of paclitaxel, carboplatin, and gemcitabine showed promising efficacy against metastatic NPC but at the expense of considerable toxicity.     

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．     

培美曲塞与多西他赛联合铂类一线治疗晚期肺腺癌的疗效比较

背景与目的：目前,晚期肺腺癌主要依靠以化疗为主的综合治疗。培美曲塞作为一种多靶点抗叶酸制剂,与铂类药物联合应用治疗晚期肺腺癌,因其疗效好、不良反应轻而受到推崇。本研究比较培美曲塞与多西他赛联合铂类一线治疗晚期肺腺癌的效果及不良反应。方法：将50例晚期肺腺癌患者随机分为培美曲塞＋顺铂(PC)组和多西他赛＋顺铂(TP)组。每组各25例患者。PC组：培美曲塞500 mg/m²静脉滴注,第1天;顺铂75 mg/m²静脉滴注,第1天。TP组：多西他赛75 mg/m²静脉滴注,第1天;顺铂75 mg/m²静脉滴注,第1天。两组1个周期均为21 d。比较两组的有效率(response rate,RR)、疾病控制率(disease control rate,DCR)、无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)。测定外周血T淋巴细胞亚群活性,评价两组患者免疫功能。结果：50例患者均可评价疗效及不良反应,两组均无完全缓解(complete remission,CR)病例,部分缓解(partial remission,PR)20例,疾病稳定(stable disease,SD)17例,疾病进展(progressive disease,PD)13例。PC组与TP组的RR、DCR、PFS和OS差异均无统计学意义(P>0.05)。PC组治疗后与TP组相比,CD3^＋、CD4^＋、CD4^＋/CD8^＋T细胞和NK细胞活性均升高,CD8^＋T细胞活性降低,但差异无统计学意义(P＞0.05)。两组的不良反应主要为骨髓抑制和消化道反应,PC组Ⅲ~Ⅳ级不良反应白细胞减少、血小板减少、消化道症状和乏力的发生率低于TP组,差异有统计学意义(P<0.05)。结论：培美曲塞与多西他赛联合顺铂治疗晚期肺腺癌的临床疗效相当,但前者可降低不良反应发生率。     

Platinum-Based Chemotherapy Followed by Radiation Therapy of Locally Advanced Nasopharyngeal Cancer a Retrospective Analysis of 39 Cases

A retrospective analysis was performed of 39 patients with locally advanced nasopharyngeal cancer treated with combined chemotherapy and radiation therapy during the last five years, at our departments. There were 26 men and 13 women with median age 55 (24-75) years. Histology was squamous cell carcinoma in 6 patients and undifferentiated carcinoma in the remaining 33 patients. Induction chemotherapy consisted of either regimen A (cisplatin 100mg/m² day 1, 5-FU 1000mg/m² days 2-6 as continuous infusion, bleomycin 15 mg days 15 and 29 i.m., mitomycin 4mg/m² day 22 and hydroxyurea 1 000mg/m² daily days 23-27) or regimen B (carboplatin 300mg/m² day 1, 5-FU 1 000mg/m²days 1-5 as continous infusion and methotrexate 1.2g/m² day 14 with leucovorin rescue). After completion of induction chemotherapy 13 patients (33%) had complete remission (CR) and 19 (49%) partial remission (PR). The CR rate was increased after radiation therapy to 72%. Survival rates were 88% at 12 and 78% at 24 months. Median time to progression was 29.5 months. In conclusion, induction chemotherapy with a platinum-based regimen followed by radiation therapy achieved a high rate of local control. If the treatment also prolongs survival must, however, be studied by randomized trials.     

Phase II study with gemcitabine, ifosfamide and cisplatin in advanced non-small cell lung cancer

The aim of the present study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine, ifosfamide and cisplatin (GIP), administered every 3 weeks, in patients with inoperable non-small cell lung cancer (NSCLC). From October 1998 to July 1999, 18 previously untreated stages IIIb (4) and IV (14) patients were enrolled into the study. Gemcitabine and ifosfamide (with mesna as uroprotection) was administered on days 1 and 6, at a dose of 1000 and 1500 mg/m², respectively; and cisplatin was given on day 1 at a dose of 60 mg/m², every 3 weeks. All 18 patients were evaluable for response and toxicity profiles. One patient achieved a complete response, and 11 patients achieved a partial response, with an overall response rate of 66.7% (95% CI, 45–89%). The main toxicity was hematological, a NCI grade 3–4 neutropenia in 16 patients (88.9%) during the treatment course. Febrile neutropenia occurred in three patients (16.6%). Grade 3 anemia occurred in eight patients (44.4%) and grade 3–4 thrombocytopenia occurred in 11 patients (61.1%). Non-hematological toxicity was mild and tolerable. No toxic death occurred. The median survival was 12.7 months and 1 year survival was 58.4%. The GIP combination chemotherapy produced a high response rate in advanced NSCLC; however, there was a relatively high percentage of hematological toxicity that still could be tolerated. A randomized trial comparing GIP to a two-drug combination of gemcitabine and cisplatin is planned.     

吉西他滨联合替吉奥治疗难治性鼻咽癌的疗效及其对免疫功能的影响

目的 评价吉西他滨联合替吉奥方案治疗难治性鼻咽癌的临床疗效,及化疗前后外周血T淋巴细胞亚群的动态变化。方法 回顾性收集42例难治性鼻咽癌患者资料,给予吉西他滨联合替吉奥化疗。吉西他滨1.0 g/m²,分别于第1天和第8天静脉滴注;替吉奥40 mg/m²,口服,2次/天,d1~14。21天为1周期,所有病例均接受至少2周期化疗。收集患者化疗前后外周血,检测患者化疗前后的T细胞亚群变化。采用单因素对数秩检验（Log rank test）进行生存分析和多因素Cox比例风险回归模型分析预后因素。结果 42例患者均完成计划化疗方案和随访。其中完全缓解1例,部分缓解21例,稳定12例,进展8例,有效率为52.4%（22/42）,疾病控制率为81.0%（34/42）,中位疾病进展时间为6.8月,中位生存时间为14.6月。常见不良反应有骨髓抑制、胃肠道反应、皮疹、疲劳等,无治疗相关死亡。与进展组患者比较,有效组患者化疗后CD3⁺、CD3⁺CD4⁺细胞百分比升高,CD4⁺/CD8⁺升高。多因素分析表明是否出现肝转移是影响预后的独立危险因素。结论 吉西他滨联合替吉奥治疗难治性鼻咽癌患者疗效肯定,不良反应可以耐受,是否出现肝转移是影响预后的独立危险因素。化疗有效者外周血T淋巴细胞亚群变化更为明显。     

Partially hyperfractionated accelerated radiotherapy and concurrent chemotherapy for advanced nasopharyngeal carcinoma

A newly designed concomitant chemoradiotherapy was undertaken to assess the feasibility and efficacy for advanced nasopharyngeal carcinoma (NPC).

Sixty-three patients with biopsy-proven NPC were entered in this Phase II trial from March 1992 to November 1993. Most patients present with Stage IV disease (93.4%) and poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic type. Radiotherapy was delivered using a telecobalt unit and 10 MV x-rays and by altered fractionation (72–74 Gy/45 fractions/6 weeks). Chemotherapy with cisplatin 75 mg/mm², 2 h infusion at day 1, followed by 5-FU 400 mg/m²/day, continuosly infused for 4 days was given concurrently during the first and fifth weeks of radiotheraphy.

The major toxicity was mucositis (61% belong to Grade 3, 31% to Grade 2). Weight loss, leucopenia, and skin reaction were frequently encountered. Three patients withdrew from treatment at 15, 25, and 55.5 Gy, three patients interrupted the radiotherapy for 1–4.5 weeks, and two patients refused the second cycle of concomitant chemotherapy due to toxicities. The initial tumor response showed 100% overall response rate, with 90.5% complete response. After a median follow-up tiem of 38 months, five patients failed at the primary and/or neck (four recurrent and one persistent), and 14 patients developed distant metastases alone. The 3-year primary disease-free, regional disease-free, distant disease-free, and overall survival rates are 89.1, 92.8, 74.3, and 73.6%, respectively. The late complication rate is acceptable so far.

Our data indicates that concurrent chemoradiotherapy for advanced NPC is both feasible and effective, with acceptable toxicities. Distant metastases are the major site of treatment failure. Postradition adjuvant chemotherapy to eradicate subclinical distant metastasis should be further studied.     

吉西他滨联合多西他赛治疗晚期软组织肉瘤11例

  目的  探讨吉西他滨联合多西他赛治疗晚期软组织肉瘤的临床疗效。  方法  收集11例对一线化疗药物耐药的晚期软组织肉瘤患者,应用吉西他滨（剂量为900 mg/m2,第1和第8天）联合多西他赛（剂量为100 mg/m2,第8天）每3周重复给药。如患者曾经接受放疗,吉西他滨剂量减为675 mg/m2,多西他赛剂量减为75 mg/m2。  结果  接受化疗的患者总有效率（CR+PR+SD）为54.5%。中位随访时间为19（1~36）个月,中位总生存期为15.4个月（95%CI:8.012~21.598）和中位无进展生存期为8.4个月（95%CI:7.342~8.768）。12个月和36个月的生存率分别是81.8%和27.3%。吉西他滨联合多西他赛治疗软组织肉瘤最常见的非血液学不良反应是黏膜炎,对症处理明显好转。  结论  吉西他滨联合多西他赛作为二线化疗药物治疗晚期软组织肉瘤患者具有较好的临床疗效,且有较好的耐受性,本研究结论为该方案的大样本临床试验提供了依据。      

Etoposide, Cisplatin, Bleomycin, And Cyclophosphamide (Ecbc) As First-Line Chemotherapy for Poor-Risk Non-Seminomatous Germ Cell Tumors

Sixty-one patients with advanced metastatic non-seminomatous germ cell tumors were treated with etoposide 120 mg/m², cisplatin 30 mg/m², bleomycin 12 mg/m², and cyclophosphamide 300 mg/m² daily for four days; and additional bleomycin bolus injection of 15 mg was given on day 1. Fifty patients (82%) were treated with four to six courses at 3-week intervals. Forty patients (66%) attained complete remission, and further 7 patients (11%) achieved a marker-negative partial remission accounting for a favorable response rate of 77%). Hematologic toxicity was considerable and there were two treatment-related deaths. After a median observation time of 47 months (range 12 to 108 months), 43 patients were alive, of which 38 had continuous complete remission, one a second complete remission, two marker-negative stable disease and two progressive disease. Our results are similar to those reported by other investigators for poor-risk metastatic non-seminomatous germ cell tumors treated with dose-intensified regimens.     

Phase I trial of fixed dose rate infusion gemcitabine with gefitinib in patients with pancreatic carcinoma

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine using a fixed dose rate infusion (FDRI) in combination with gefitinib in patients (pts) with pancreatic adenocarcinoma (PCa). Patients and methods: Patients with advanced PCa were given gemcitabine at the FDRI of 10 mg/m²/min IV on Days 1, 8, and 15 of a 28-day cycle. Dose levels of 1000, 1200, and 1500 mg/m² were evaluated. Oral gefitinib 250 mg was given daily. DLTs were defined as 2 instances of Grade 3 hematologic or 4 nonhematologic or any Grade 4 hematologic toxicity. At least 4 patients were treated at each dose level. Dose escalation occurred in the absence of DLTs. Results: Five women and 8 men were enrolled. Median age was 59 and performance status 1. All had metastatic disease. Four patients received prior adjuvant chemoradiation for PCa, and one chemotherapy for lung cancer. Median cycles were 4 per patient. The MTD was 1,200 mg/m². Toxicity was predominantly hematologic. At 1,500 mg/m², 1 patient had Grade 4 granulocytopenia and 3 patients Grade 3 granulocytopenia. Overall, 8 patients (60 percent) developed Grade 1 or 2 acneiform rashes. One patient had Grade 3 vomiting; no significant diarrhea or liver toxicity was seen. There were no objective responses seen. Median time to progression and overall survival were 4.57 months and 7.13 months, respectively. Conclusion: Combining FDRI gemcitabine with gefitinib is feasible and tolerable. The recommended dose of gemcitabine is 1,200 mg/m² when used with gefitinib 250 mg daily.