小剂量HA方案治疗老年急性髓细胞性白血病临床观察

[目的]研究小剂量HA方案治疗老年急性髓细胞白血病（AML）的临床疗效及安全性。[方法]应用小剂量HA方案（高三尖杉酯碱每天1mg,静脉滴注,第1-14d;阿糖胞苷12．5mg,皮下注射每12h一次．第1～14d;4周为1个疗程）治疗初发的老年急性髓细胞性白血病患者10例,1个疗程后观察疗效及毒副反应。[结果]10例患者中,完全缓解6例（60％）,部分缓解1例（10％）．总有效率为70％。骨髓抑制相对较轻,未见严重的非血液系统毒副反应。[结论]小剂量HA方案诱导缓解治疗老年AML具有较好的有效率,毒副反应耐受较好,可作为年龄较大、一般状况较差、有多种或较重合并症的老年AML患者的初始治疗方案选择。     

Mitoxantrone as first-salvage chemotherapy in relapsed breast cancer

Mitoxantrone was administered at the dose of 14 mg/m2 i.v. every 3 weeks to 25 consecutive women with measurable progressive disease who relapsed after adjuvant CMF and endocrine therapy. The treatment plan consisted in the delivery of 6 cycles, unless disease progression or severe toxicity occurred. All patients were evaluable for drug response and toxicity. One patient achieved complete remission and 6 partial remission, for a total response rate of 28%. Objective tumor response was observed in all major sites of disease. The median time to achieve remission was 3 months. The median duration of response was 7 months (range, 5-39+), and the median survival for the entire group was 10 months (range, 3-39+). Results were influenced only by the duration of disease-free status from the end of adjuvant CMF chemotherapy. In fact, all tumor responses were documented in woman with free intervals exceeding 1 year (7 of 17 or 41%). Treatment was generally well tolerated, with 10 patients developing leukopenia at some time during treatment. Only 2 patients received less than 75% of the projected dose because of granulocytopenia. Complete alopecia occurred in only 2 cases. Three patients developed a fall greater than 15% in left ventricular ejection fraction, but no episode of congestive heart failure was observed. We conclude that mitoxantrone is an effective and safe drug which can be utilized in women relapsing after adjuvant CMF.     

A phase II study of etoposide, doxorubicin, and carboplatin in the treatment of advanced gastric cancer

Many phase II studies have reported improved response rates with severe toxicity of etoposide, doxorubicin (Adriamycin), and cisplatin in advanced gastric cancer. In an attempt to obtain a better regimen with high efficacy and less toxicity, a combination regimen of etoposide, doxorubicin, and carboplatin (EAC) had been developed and evaluated in this phase II study. Forty-six patients with advanced gastric cancer were enrolled in the study. The treatment consisted of doxorubicin 20 mg/m2 given intravenously on days 1 and 7, etoposide 70 mg/m2 intravenously on days 4, 5, and 6, and carboplatin 200 mg/m2 intravenously on days 2 and 8. Therapy was repeated every 4 weeks. Patients who had stable disease or who responded, received an additional two to six cycles of therapy. Among 45 patients evaluable for response and toxicity, there was a 49% objective response rate, including 7% complete remission and 42% partial response. There was 11% stable disease and 27% progressive disease. Among 11 patients with lymph node metastasis only after a curative gastrectomy, there was an 82% objective response rates with 27% having complete remission and 55% having partial response. The median follow-up was 16 months. The median survival duration of all 45 patients was 11 months. The median time to progression was 5 months. The main toxicity was myelosuppression, with a high incidence of 82% leukopenia but only 9% of grades III to IV. Gastrointestinal toxicity was mild, with a low incidence of 42% nausea and vomiting and only 2% of grades III to IV. There were no chemotherapy-related deaths. With mild and tolerable toxicity, the EAC regimen in our study has active antitumor activity in advanced gastric cancer, which may have a positive influence on long-term survival time. It has a high efficacy, especially in patients with lymph node metastasis only after a curative gastrectomy. This regimen deserves further clinical studies for testing activity and toxicity in advanced gastric cancer.     

美罗华联合DICE方案治疗复发和难治性侵袭性B细胞淋巴瘤

目的观察美罗华联合DICE方案治疗国人复发和难治性侵袭性B细胞非霍奇金淋巴瘤的疗效及不良反应。方法全组共15例采用美罗华375mg/m2,于化疗第1个周期前1天开始,每周输注1次,连续4次。化疗采用DICE方案,化疗每3周循环一个周期,3个周期后评价疗效及不良反应。结果15例患者中,有14例可以评价客观疗效,其中获得CR7例(50.0%),PR4例(28.6%),总有效率78.5%,1年无进展生存(PFS)率为50.1%,1年总生存(OS)率为64.3%。不良反应均可耐受,主要为输注相关的不良反应和化疗相关的血液学毒副反应。结论经过初步应用,可以得出美罗华联合DICE方案是治疗国人复发和难治性侵袭性B细胞淋巴瘤的有效方案,完全缓解率高且毒性反应可以耐受。     

Cyclophosphamide, adriamycin, and cis-platinum (CAP) in metastatic and locally advanced breast cancer

A combination of cyclophosphamide, adriamycin, and cis-platinum (CAP) was tested in 20 previously untreated patients with locally advanced or metastatic breast cancer with the aim of assessing the ability of this platinum-containing regimen to induce a high complete remission rate. The drug regimen was given on a 3/week schedule at the following doses: cyclophosphamide 200 mg/m2 i.v. on days 1, 2, 3; adriamycin 40 mg/m2 i.v. or day 1 and cis-platinum 20 mg/m2 i.v. plus hydration on days 1, 2, 3. In the absence of progression, six cycles of CAP were planned and response was evaluated at that time. Thirteen of 20 patients achieved partial remission (65%) but only one obtained complete remission (5%). Overall median duration of response was 9 months (range 4-20 + months). Tumor response was mainly documented in soft tissues (primary tumor: 14 of 16; other sites: 19 of 20). Grade II leukopenia was documented in 60% of patients. All patients experienced moderate to severe gastrointestinal toxicity and alopecia was universal. No renal toxicity was observed. Although CAP regimen at the given dose schedule induced a high overall response rate (70%), the complete remission rate in this limited number of patients was lower than expected. These results do not appear superior to those achieved with conventional drug regimens.     

吉西他滨联合长春瑞滨治疗蒽环类和紫杉类耐药的晚期乳腺癌疗效和安全性评价

目的评价吉西他滨联合长春瑞滨用于治疗蒽环类和紫杉类治疗失败的晚期乳腺癌的疗效和安全性。方法20例经蒽环类和紫杉类治疗失败的晚期乳腺癌患者,采用吉西他滨联合长春瑞滨方案（GN）治疗：吉西他滨1 000 mg/m2静脉滴注,第1、8天;长春瑞滨25 mg/m2第1、8天,每3周重复。治疗至少2疗程,最多6疗程,每2个疗程后复查CT评价疗效,同时记录不良事件。结果1例患者因皮疹和骨髓抑制而终止治疗,其余19例患者均可评价疗效。完全缓解（CR）1例,部分缓解（PR）5例,稳定（SD）9例,进展（PD）4例。有效率（CR＋PR）为31.6%（6/19）,临床获益率（CR＋PR＋SD）为78.9%（15/19）。主要毒副反应为Ⅰ~Ⅱ度骨髓抑制、胃肠道反应、皮疹和末梢神经毒性。结论吉西他滨联合长春瑞滨是经蒽环类和紫杉类治疗失败晚期乳腺癌的有效方案,安全性良好。     

A pilot study of mitomycin, cisplatin and continuous infusion 5-fluorouracil (MCF) in advanced non-small-cell lung cancer.

A pilot study of continuous infusional 5-fluorouracil 200 mg m-2 per 24 h by ambulatory pump and Hickman line for the entire treatment cycle with mitomycin C 8 mg m-2 i.v. on day 1 and cisplatin 75 mg m-2 i.v. on day 1, both repeated every 28 days, was carried out in 31 previously untreated patients with advanced non-small-cell lung cancer (NSCLC). Of 31 patients assessable for response, one attained a complete remission and eight a partial remission, an overall response rate of 29%. Haematological toxicity was minimal, with only 3% of patients developing WHO grade III/IV neutropenia and 13% grade III/IV thrombocytopenia. Significant side-effects included moderate to severe emesis (41%), mucositis (34%), diarrhoea (31%) and palmar-plantar syndrome (14%). Seven patients (23%) had Hickman line complications requiring line removal. Continuous infusional chemotherapy with this regimen is active in advanced non-small-cell lung cancer, but its complexity and associated treatment toxicity offer little advantage over equally active but simpler and less toxic cisplatin-based regimens.     

脂质体多柔比星治疗淋巴瘤患者的疗效及安全性分析

背景与目的:蒽环类药物在淋巴瘤化疗中有很重要的地位,但相关不良反应限制了其在临床中的应用,尤其是心脏毒性。本文旨在分析脂质体多柔比星联合治疗淋巴瘤患者的有效率及安全性。方法:回顾性分析2006年1月—2011年10月在北京大学肿瘤医院淋巴肿瘤科住院并接受脂质体多柔比星联合化疗的68例患者的临床资料。其中初治患者47例,复治患者21例。应用SPSS 17.0统计软件统计分析治疗有效率和治疗相关不良反应,评价脂质体多柔比星的疗效及安全性。结果:68例患者中弥漫大B细胞淋巴瘤(diffuselarge B-cell lymphoma,DLBCL)42例。总有效率(ORR)为73.5%,其中完全缓解(CR)率57.4%,部分缓解(PR)率19.1%。初治DLBCL的ORR率为74.3%,CR率为60%,其中应用R-CCOP方案治疗患者的ORR率为81.5%,CR率为66.7%。骨髓抑制是最常见不良反应,3～4级粒细胞减少症的发生率55.9%;心电图异常发生率54.4%,3例患者出现心功能异常。仅1例伴有严重内科疾病的患者出现肺部感染并死亡。结论:使用脂质体多柔比星治疗淋巴瘤的有效率和安全性均较好。     

Etoposide, adriamycin, and cisplatinum (EAP) combination chemotherapy for advanced gastric cancer. A phase II trial by the "Chemotherapiegruppe Gastrointestinaler Tumoren (CGT)"

In a multicenter trial, 49 patients with histologically proven advanced gastric cancer were treated with a combination chemotherapy consisting of etoposide 120 mg/m2 d 4, 5, 6 adriamycin 20 mg/m2 d 1, 7 and cisplatinum 40 mg/m2 d 2, 8. Therapy was repeated every 4 weeks, 45 patients were evaluable for response after 8 weeks of treatment. Eight patients achieved a partial remission (PR: 18%), 17 patients had no change (NC: 38%), and 20 patients showed tumor progression (P: 44%). Four patients with primarily inoperable tumor and without distant metastases who achieved a partial remission, underwent second look operation with curative intention. All 4 patients died within 12 months after second look operation due to tumor recurrence. Median survival time of all patients was 9 months. Toxicity was considerable. WHO grade 3/4 toxicity appeared in 20-30% of patients (nausea, vomiting, loss of appetite, leucopenia). After 3 cycles complete alopecia was present in 70% of patients. Severe infection, requiring treatment, occurred in 10 patients. Five patients discontinued therapy because of intolerable subjective toxicity. The observed response rate of 18% objective partial remissions is disappointing and does not give support to the communications reporting response rates over 50% with EAP and other regimens including cisplatinum. In conclusion, and considering the high subjective and objective toxicity of this regimen, it can not be recommended for standard use in patients with advanced gastric cancer.     

A phase II study of 5-fluorouracil and leucovorin in advanced carcinoma of the esophagus.

Thirty-five patients with advanced epidermoid carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) 425 mg/m2 and leucovorin 20 mg/m2, day 1-5 every 28 days. Six patients had a partial response (95% confidence limit, 7-35%) with a median response duration of 32 weeks. The median survival time of the patients on study was 14 weeks. The toxicity was acceptable, with only two patients experiencing severe hematologic toxicity and one patient experiencing severe nausea and vomiting. The addition of leucovorin at this dose level in this population of patients with advanced disease does not appear to enhance the activity of 5-FU for patients with squamous cell cancer of the esophagus. Since only a small percentage of patients experienced significant toxicity, a higher response rate could be achieved in patients treated with the maximally tolerated dose.     

奈达铂治疗耐药性鼻咽癌和非小细胞肺癌

目的：研究国家二类新药奈达铂单药治疗顺铂(DDP)耐药性晚期鼻咽癌和非小细胞肺癌的临床疗效及安全性。方法：奈达铂单药治疗耐药性鼻咽癌鼻咽癌6例、非小细胞肺癌3例。奈达铂100mg／m^2加入500ml无菌生理盐水中，静脉滴注2小时，每3--4周重复一次。结果：9例入组患者均可评价疗效。鼻咽癌6例中1例CR，2例PR，有效率为50％；非小细胞肺癌3例中有1例PR。总RR为45．5％。主要毒副作用是对血小板及白细胞生成的抑制作用，恶心、呕吐反应较小，对肾脏的损伤、胃肠道性毒性作用及周围末梢神经等毒性较轻，肝肾功能影响不明显。结论：奈过铂单药对DDP耐药的鼻咽癌或非小细胞肺癌仍有较高的疗效，且多数患者耐受良好．     

Dual modulation of UFT with leucovorin and hydroxyurea in metastatic colorectal cancer

The aim of the study was to investigate the possibility of dual modulation of UFT with leucovorin and hydroxyurea in a phase II trial of metastatic colorectal cancer. A total of 77 patients with measurable disease were included. UFT (300 mg/m2) was given with a fixed dose of 1-leucovorin (22.5 mg daily) and hydroxyurea (0.5 g daily) for 28 days followed by a 7 days' rest period. Treatment continued until progression or unacceptable toxicity. Sixty-three patients were evaluable for response. One patient (1.6%) had a complete remission and 13 (20.6%) a partial response for an overall response rate of 22.2%. The treatment was well tolerated. No significant bone marrow depression occurred. Grade 2 gastrointestinal toxicity was recorded in 28.5% of the patients, and grade 3 in 12.9%. The median time to progression was 6.8 months and the median crude survival was 11 months. In conclusion, hydroxyurea did not appear to increase either the response rate or the toxicity. Phase III trials along the same line cannot be recommended.     

Methyl-Gag, Ifosfamide, Methotrexate and Etoposide (Mime) as Salvage Therapy for Non-Hodgkin's Lymphomasa Swedish national prospective study

One hundred and two patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) were treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) in accordance with a prospective protocol. Of 75 patients with high-grade malignant NHL (median age 57 years, range 21-79), 15 patients (20%) obtained a complete response (CR) and 27 patients (36%) a partial remission (PR), giving an overall response rate of 56%. The remissions were usually short when not consolidated with ABMT or radiotherapy. The probability of progression-free survival after 2 years was 13%, and the cause-specific survival was 23%. Of 27 patients with low-grade NHL (median age 46 years, range 37-86), 7% had a CR and 37% a PR giving a response rate of 44%. The remissions were again usually short when not consolidated, and the probability of progression-free survival at two years was 11%, and the cause-specific survival 26%. The main toxicity was hematological with septicemia in 20% of the patients and other severe infections in 19%. Fifteen patients (11 high-grade NHL and 4 low-grade NHL) were consolidated with high-dose therapy followed by ABMT, of whom 6 are in continuous CR. We conclude that MIME can induce remissions in NHL patients, and that the remission rates are comparable with those of many other salvage regimens. The remissions are, however, generally of short duration and need consolidation. There was considerable toxicity therefore patients not suitable for ABMT preferably should be treated with less toxic salvage regimens.     

改良TCD方案治疗初治多发性骨髓瘤26例临床观察

目的观察改良TCD方案(小剂量沙利度胺和地塞米松联合环磷酰胺）治疗初治多发性骨髓瘤的临床疗效。方法应用改良TCD方案6周期治疗26例初治多发性骨髓瘤患者,应用血清蛋白电泳、免疫固定电泳、骨髓细胞形态学和β2-微球蛋白评估治疗效果,同时观察药物的不良反应。结果CR 6例,nCR 7例,PR 5例,轻度反应2 例;总有效率69.2%,总反应率76.9%。化疗不良反应轻,无治疗相关性死亡。结论 改良TCD方案治疗初治多发性骨髓瘤疗效较好,不良反应较少,值得临床推广应用。     

A phase II trial of recombinant interferon alpha-2b and cisplatin in metastatic melanoma

In this phase II study 37 patients with metastatic melanoma were treated with cisplatin 100 mg/m2 every three weeks and interferon alpha-2b 10 MU subcutaneously three times weekly; 125 cycles were administered. Thirty-four patients were evaluable for response and all 37 patients were assessable for toxicity. Four patients stopped treatment with cisplatin because of severe nephrotoxicity, and six patients stopped therapy because of other toxicities. Response rate was 6/34 = 18% (95%) CI (confidence interval): 7%-35%). One patient reached complete response lasting 27+ months. Five patients obtained partial responses with a median duration of response of 7 months (range 5-15+ ). Median time to progression was 2.3 months (range 1-27+). Median survival was 5 months (range 1-27+). We conclude that the combination of high-dose cisplatin 100 mg/m2 and interferon alpha-2b is associated with unacceptable toxicity. Haematological toxicity and nephrotoxicity were pronounced and the response rate was meagre and not encouraging.     

Evaluation of cyclophosphamide, adriamycin, and cis-platinum (CAP) in patients with disseminated prostatic carcinoma. A phase II study

A prospective study was conducted to evaluate response rate and toxicity of the combination of cyclophosphamide, adriamycin, and cis-platinum in patients with disseminated hormonally resistant prostatic carcinoma. Twenty-two patients were entered in the study: 19 were evaluable for response. One patient achieved partial remission while 14 (73%) had stable disease. Four patients had progressive disease. Patients with stable disease and partial remission had subjective improvement and survived significantly (p less than 0.03) longer than patients with progressive disease (58 weeks vs. 22 weeks). Toxicity was mainly hematological, and one patient died from sepsis secondary to leukopenia. Nausea and vomiting was moderate to severe, with one patient refusing cis-platinum for that reason. Renal toxicity was tolerable and reversible. Lack of good measurable disease makes generalization difficult, but pointers from animal models, along with the biological activity suggested by our results, make this a worthwhile combination to be considered for a trial in a larger population with measurable disease or in a randomized trial vs. the more effective single agent.     

Phase II study of multiple daily fractionations in the palliation of advanced pelvic malignancies: preliminary report of RTOG 8502

This Phase II protocol was designed around the format of a previously reported study for the palliation of advanced pelvic malignancies (RTOG 7905). The large dose per fraction (1000 cGy) of the first study unexpectedly demonstrated frequent late gastrointestinal toxicity and was replaced in the present study by 2 days of twice daily fractionation (370 cGy/fraction totaling 1480 cGy/course) based on linear quadratic consideration of acute and late toxicities. The interval between courses of 4 weeks was retained and the total dose for three courses was 4440 cGy. A total of 152 patients were entered of which 142 have sufficient follow-up information for analysis. Fifty-nine percent of the patients completed all three courses, 20% completed two courses, and 20% received only one course. The primary sites were: gynecological (39.4%); colorectal (32.4%); genitourinary (24.7%); and other (2.8%). The best overall response was: complete remission (10%); partial remission (22%); no change (24%); progression (10%); and unknown (27%). For the patients completing all three courses, the response was: complete remission (14%); partial remission (31%); no change (40%); progression (7%); and unknown (8%). Median survival was 4.5 months and the actuarial survival at 12 months is 19%. In RTOG 7905, 90% of the late toxicities appeared by 12 months. For RTOG 8502, there were 32 patients alive at 9 months and 19 patients alive at 12 months available for evaluation of late toxicity. There has been one late grade 3 GI toxicity reported and only one acute grade 3 gastrointestinal toxicity. Even if the true rate of late toxicity for 8502 were 20%, the chance of seeing none or one toxicity would be 0.007. This toxicity report represents a marked reduction of the grade 3 and 4 late toxicity seen in RTOG 7905 (37% at 9 months and 45% at 12 months) without lowering the tumor response rate. The interval between courses in both protocols allows for potential tumor proliferation. To test for the effect of tumor proliferation, RTOG 8502 is continuing as a Phase III randomization between 4 weeks and 2 weeks separation.     

Mitomycin-C, methotrexate, bleomycin and cis-diamminedichloroplatinum II in the chemotherapy of advanced squamous cancer of the head and neck

Thirty-four patients with advanced squamous cancer of the head and neck were treated with an outpatient regimen combining mitomycin-C, cis-diamminedichloroplatinum (II), methotrexate and bleomycin. Five had complete remissions and 15 partial remissions, for an overall response rate of 59%. Responses were noted on 11 of 13 patients (85%) with disease above the clavicles without prior irradiation. Median duration of partial remission was four months. Response rate was independent of age, performance status, presence of distant metastases and primary site. Hematologic toxicity was substantially more severe with this program than had been observed in a prior study using the same regimen without mitomycin-C. Since neither complete nor partial response rates, nor response durations improved with the addition of mitomycin, we conclude that it adds little to the efficacy of the other three agents.     

High-dose cytosine arabinoside: treatment and cellular pharmacology of chronic myelogenous leukemia blast crisis

Twenty-one patients with chronic myelogenous leukemia (CML) in blastic transformation underwent 22 remission induction attempts with high-dose cytosine arabinoside (ara-C), administered as a two-hour infusion of 3 g/m2 for six to 12 doses. Ara-C doses were administered every 12 hours in 15 patients and every six to ten hours in six patients. Median patient age was 35 years (range, 20 to 62). The median duration of benign phase was 25 months (range, 0 to 167). Morphology of blast crisis blast cells was myeloid in 15 patients and lymphoid in six. Five patients achieved complete remission (CR), three had partial remission (PR), and one had hematologic improvement, for an overall response rate of 41%. Median remission duration was 2.5 months (range, 0.5 to 6 months). Survival duration was 6 months for responding patients and 1.5 months for those with resistant disease. The response rate was similar for patients with myeloid and lymphoid blast crisis (31% v 50%, respectively). The response rate was significantly higher for patients whose benign phase was less than 1 year (75% v 21%, P = .05) and who had prolonged marrow aplasia after ara-C (86% v 27%, P = .05). Myelosuppression was the major dose-limiting toxicity, and cerebellar toxicity occurred in two patients. Intracellular ara-C 5'-triphosphate (ara-CTP) levels were similar in blood and bone marrow leukemic cells and were slightly greater in the cells of responding patients compared to those with resistant disease. We conclude that high-dose ara-C is an effective regimen for CML blast crisis, resulting in a substantial response rate but modest remission duration. Its combination with other agents may further improve the prognosis of patients with this resistant disease.     

High-dose cyclophosphamide followed by cisplatinum in the treatment of ovarian cancer

Summary Twenty patients with previously untreated ovarian cancer received intensive chemotherapy after initial surgery. Treatment comprised two courses of cyclophosphamide at 7 g/m² with mesna, re-evaluation with second-look laparotomy where appropriate, followed by five courses of cisplatin at 100 mg/m². Three patients achieved pathologically documented complete remission (PDCR) with high-dose cyclophosphamide, and eight patients achieved partial remission. Fifteen patients went on to receive cisplatin. Nine of these patients had no assessable disease; of six patients who were assessed for response two achieved PDCR and three achieved partial remission. The overall response rate to the sequential regimen was 14/20 (70%). High-dose cyclophosphamide was associated with marked haematological toxicity, which was cumulative and fatal in two patients. The median duration of first remission was 14 months, and the median duration of survival was 20 months. It is concluded that sequential treatment with high-dose cyclophosphamide and cisplatin appears to be no more effective than conventional treatment in advanced ovarian cancer, judging by the PDCR rate and median survival achieved.