Sequential versus alternating chemotherapy for high-grade non-Hodgkin's lymphomas: preliminary results of a phase III multicentre trial

In a multicentre phase III trial 105 previously untreated patients with high-grade non-Hodgkin's lymphomas stage II-IV were randomized to receive either 4 cycles of CHOEP (cyclophosphamide 750 mg/m2 i.v. day 1, doxorubicin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, etoposide 100 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) (treatment arm A), or 4 cycles of chemotherapy with hCHOP (cyclophosphamide 1,200 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. days 1 + 2, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5) alternating with IVEP (ifosfamide 1,500 mg/m2 i.v. days 1-5, vindesine 3 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) in treatment arm B. After 4 cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 86/105 patients (82%) with 88% CR in arm A vs. 76% CR in arm B. During a median follow-up of 11 months (range 2-31 months) 13 patients relapsed (6 patients arm A, 7 patients arm B). The overall survival at 30 months is projected to be 72% vs. 83% for arm A and B respectively. Disease-free survival is projected to be 78% in arm A and 45% in arm B at 28 months. So far, the differences in CR, survival and disease-free survival are not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

B-CHOP与CHOP方案对老年复发性套细胞淋巴瘤患者的疗效比较

目的 对比硼替佐米联合CHOP（B-CHOP）方案和CHOP方案对老年复发性套细胞淋巴瘤患者的疗效。方法 收集2009年1月至2015年1月老年复发性套细胞淋巴瘤患者38例,随机分为试验组（B-CHOP方案）和对照组（CHOP方案）,每组各19例。试验组采用B-CHOP方案治疗：硼替佐米1.6 mg／m2静推,第1、8天;环磷酰胺750 mg／m2静滴,第2天;阿霉素50 mg／m2静滴,第2天;长春新碱 1.4 mg／m2（最大剂量为2 mg）静滴,第2天;强的松100 mg／天口服,第2～6天。对照组采用CHOP方案：环磷酰胺750 mg／m2静滴,第1天;阿霉素50 mg／m2静滴,第1天;长春新碱 1.4 mg／m2（最大剂量为2 mg）静滴,第1天;强的松100 mg／天口服,第1～5天。两组均以28天为1周期,共化疗8个周期。分别于第4、8个周期化疗完成后采用非霍奇金淋巴瘤国际疗效判断标准进行评价,根据随访资料分析远期生存情况。结果 试验组化疗4个周期后获完全缓解（CR）10例、部分缓解（PR）4例、无反应（NR）3例、进展（PD）2例,8个周期后获CR 12例、PR 4例、NR 1例、PD 2例;对照组化疗4个周期后获CR 3例、PR 2例、NR 10例、PD 4例,8个周期后获CR 5例、PR 3例、NR 7例、PD 4例。试验组第4、8个周期化疗完成后的有效率（RR）为73.7％和84.2％,均高于对照组的26.3％和42.1％,差异有统计学有意义（P＜0.05）。试验组的中位总生存时间为56.0个月,高于对照组的29.0个月（P＜0.05）。两组主要不良反应为发热、白细胞减少、血小板减少和周围神经炎等,且两组不良反应发生率的差异无统计学意义（P＞0.05）。结论 在改善老年复发性套细胞淋巴瘤患者的RR和OS方面,B-CHOP方案明显优于CHOP方案。     

Induction chemotherapy with cisplatin/docetaxel versus cisplatin/5-fluorouracil for locally advanced squamous cell carcinoma of the head and neck: a randomised phase II study

A combination of cisplatin and 5-fluorouracil (PF) is considered the standard induction chemotherapy regimen for squamous cell carcinoma of the head and neck (SCCHN). The present study compares the efficacy and safety of a new combination of cisplatin/docetaxel versus the PF regimen. A total of 83 chemotherapy-naive patients with locally advanced SCCHN were randomised to receive every 21 d (i) docetaxel 85 mg/m2 i.v. on day 1 and cisplatin 40 mg/m2 i.v. on days 1 and 2 (arm A) or (ii) cisplatin 100 mg/m2 i.v. on day 1 followed by 5-fluorouracil 1000 mg/m2 in 24 h continuous infusion for 5 d (arm B). A total of 287 cycles (range 1-3 per patient) were administered. Among 76 patients evaluable for response, the overall response rate in arm A was 70% (complete response (CR) 26%, partial response (PR) 44%) and in arm B 69% (CR 16%, PR 54%), respectively. Median survival in arm A was 7.6 months (95% CI: 5.8-11.1) and 9.9 months (95% CI: 7.4-14.6) for arm B. The most frequent grade 3/4 toxicity in arm A was neutropaenia (34.1%) and diarrhoea (9.8%) versus mucositis (29.3%) and neutropaenia (19.5%) in arm B. Both schedules present a similar efficacy, with different but acceptable toxicity patterns.     

FND与CHOP方案治疗进展期惰性淋巴瘤的疗效比较

目的比较FND(氟达拉滨 米托蒽醌 地塞米松)与CHOP方案治疗进展期惰性淋巴瘤的疗效与安全性。方法临床观察的终点包括缓解率(总有效率OR和完全缓解率CR),无失败生存(FFS),总体生存(OS)及毒性。40例病人随机分组,FND和CHOP组各20例。两种治疗方案均为每28天1次,共3个疗程,之后,二组病人均采用CHOP方案巩固3个疗程。FND方案为氟达拉滨25mg/m2,ivd1~5;米托蒽醌10mg/m2,ivd1;地塞米松20mg/d,ivd1~5。CHOP方案为环磷酰胺600mg/m2,ivd1;阿霉素25mg/m2,ivd1;长春新碱1.4mg/m2,ivd1和强的松50mg/m2,pod1~5。结果FND方案的完全缓解率和总有效率显著优于CHOP(OR83%vs40%,CR50%vs15%;P<0.01)。FND组的中位FFS是32个月,而CHOP组仅为15个月。两种治疗方案的耐受性均较好,只有少量的感染并发症发生。结论FND方案的完全缓解率、总有效率均显著优于CHOP,并可有效改善预后。     

Randomized trial comparing adriamycin vincristine (av) cyclophosphamide methotrexate 5-Fluorouracil prednisone (cmfp) hybrid versus av-cmfp monthly alternated in metastatic breast-cancer

194 metastatic breast cancer patients with no prior chemotherapy for advanced disease were randomized to one of two alternating schedules, fulfilling the requisites of Goldie and Coldman's hypothesis to evaluate if the earlier alternation of two non-cross resistant regimens is superior in terms of response (R), duration of R (DR), and survival (SV). Treatment: arm A: Adriamycin (A) 60 mg/m2 IV day (d) 1 and vincristine (V) 1.4 mg/m2 IV d 1 and 8 monthly alternated with cyclophosphamide (C) 100 mg/m2 p.o. d 1-14; methotrexate (M) 30 mg/m2 IV d 1 and 8; 5-fluorouracil (F) 600 mg/m2 IV d 1 and 8 and prednisone (Pr) 40 mg/m2 p.o. d 1-14. Arm B (hybrid): A 60 mg/m2 IV d 1; V 1.4 mg/m2 IV d 1; C 100 mg/m2 p.o. d 8-14; M 30 mg/m2 IV d 8; F 600 mg/m2 IV d 8 and Pr 40 mg/m2 p.o. d 8-14. Results: 87 and 89 patients are evaluable for R. Arm A: R= 59% (51/87); median DR= 13 months (m); median SV= 25 m. Arm B: R= 69% (61/89); median DR= 15 m.; median SV= 29 m. Myelosuppression was slightly more marked in arm B. Three patients had toxic-related deaths (arm A: 1; arm B: 2). Conclusions: a trend favoring an earlier alternation and higher dose intensity (DI) was found regarding to R, DR and SV. However, differences were not statistically significant.     

Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study

The aim of this randomized four-arm phase III study was to evaluate whether there is a difference in activity between regimens containing dacarbazine and regimens without dacarbazine in metastatic melanoma, whether there is a dose-effect relationship for dacarbazine, and whether non-dacarbazine-containing aggressive regimens are in any way superior to non-aggressive ones. A total of 219 patients with metastatic cutaneous melanoma were included in this study; 196 of them were evaluable for activity. The patients were randomized into four treatment arms: arm A (standard dose dacarbazine arm), vincristine 1.4 mg/m2 on day 1, carmustine (BCNU) 60 mg/m2 on day 1, and dacarbazine 300 mg/m2 per 24 h on days 2-5; arm B (high-dose dacarbazine arm), vincristine and BCNU as in arm A and dacarbazine 600 mg/m2 per 24 h on days 2-5; arm C ('aggressive' regimen without dacarbazine), vindesine 3 mg/m2 on day 1, bleomycin 7 mg/m2 per 24 h on days 1-4, and cisplatin 30 mg/m2 per 24 h on days 5-8; arm D ('non-aggressive' regimen without dacarbazine), BCNU 100 mg/m2 on day 1 and procarbazine 90 mg/m2 per 24 h on days 1-10. The four arms were well balanced with regard to patient- and disease-related characteristics. On an intend-to-treat basis, the response rate was 11 out of 49 (22%) in arm A, nine out of 47 (19%) in arm B, 16 out of 63 (25%) in arm C and nine out of 60 (15%) in arm D. There was a large overlap between the 95% confidence intervals and no significant differences in the response rates between the four arms. Median survival in the four treatment arms was 4, 5, 6 and 4 months, respectively, again with no significant differences. Median survival for responders (8, 11, 10 and 13 months, respectively) in all four arms was significantly longer than in non-responders (4, 3, 5 and 4 months, respectively). Arms A, B and C were significantly more toxic compared with arm D, which was for all practical purposes devoid of toxicities. The efficacy of all four regimens thus appeared comparable both in terms of response rate and survival. Responders in all four arms achieved a survival benefit. There does not seem to be a dose-effect relationship for dacarbazine in metastatic melanoma. Chemotherapy from arm D, might be well suited for 'fragile' or elderly patients due to the lack of toxicity.     

A phase II trial of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisolone rapidly alternating with doxorubicin and vincristine (CMFP/AV) in advanced breast cancer.

Sixty-seven patients with advanced breast cancer were prospectively entered into a Phase II trial of cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously (i.v.) on day 1, 5-fluorouracil 600 mg/m2 i.v. on day 1, and prednisolone 40 mg/m2 orally on days 1-14 (CMFP) rapidly alternating with doxorubicin 25-30 mg/m2 i.v. on day 8 and vincristine 1.4 mg/m2 i.v. on day 8 (AV). Complete responses (CR) were seen in 7 patients, partial responses (PR) in 25 (CR + PR, 48%), stable disease in 24, and progressive disease in 9. The median time to disease progression was 9.8 months, and the median survival 19.4 months. Neutropenia was the major toxicity with WHO grade 3 or 4 neutropenia in 50% of patients. CMFP/AV is a well-tolerated, effective regimen in advanced breast cancer but does not appear to be superior to CMFP alone.     

羟基喜树碱、氨甲蝶呤、5-氟脲嘧啶和醛氢叶酸联合化疗治疗晚期复发性乳腺癌

目的：观察包含羟基喜树碱的联合化疗方案治疗晚期复发性乳腺癌的疗效及毒副作用。方法： ４３例乳腺癌患者均为术后或放疗后、并且己行系统化疗结束后复发或转移复治的病例。化疗方案为羟基喜树碱１０ｍｇ／ｍ２静滴,第 １—５ ８;氨甲喋呤 １００ｍｇ静冲,第 １日、醛氢叶酸 １５０ｍｇ／ｍ２第 ２～ ４ 日,静滴; ５－氟脲嘧啶 ５００ｍｇ／ｍ２静滴,第１－５日;每２８日为一周期,连用两个周期以上。结果：总有效率４７％,１年生存率５４％,中位生存期为１９个月。主要毒副作用为轻度的血液和消化道反应。结论：含羟基喜树碱的ＨＭＬＦ方案是治疗晚期复发性乳腺癌有效且毒性较小的联合化疗方案。     

MTX-HOPE (methotrexate, hydrocortisone, vincristine, sobuzoxane, and etoposide) as a low-dose salvage chemotherapy for recurrent or refractory non-Hodgkin's lymphoma

We conducted a clinical study of MTX-HOPE (day 1, methotrexate 20 mg per os (po); day 2, hydrocortisone 100 mg intravenous (iv), vincristine 1 mg iv; day 3,4 sobuzoxane 400 mg po; etoposide 25 mg po, repeating every 2 or 3 weeks) in 14 relapsed or refractory patients with non-Hodgkin's lymphoma. Ten responders were obtained 5 CR and 5 PR), and heavily treated patients were included in the responders. The median duration of over all survival which was estimated with Kaplan-Meier curve was 11.1 months (range, 2-18+ months), and the median duration of response was 6.9 months (range, 0.8+ -16.4+ months).Out of the 14 patients,eleven were treated with this regimen in an outpatient setting. Grade 4 neutropenia and thrombocytopenia were observed in 4 and 2 patients,and grade 3 GPT-elevation and stomatitis in two and one, respectively. This newly developed MTX-HOPE therapy may be a promising treatment option for such patients as are intolerable for high-dose chemotherapies with PBSC rescue or wish for outpatient therapy.     

奥沙利铂或伊立替康联合5-氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌临床研究

目的观察奥沙利铂（L—OHP）或伊立替康（CPT-11）联合5-氟尿嘧啶（5-Fu）和亚叶酸钙（CF）治疗晚期结直肠癌的临床疗效和患者不良反应。方法76例均经细胞学或病理确诊为晚期结直肠癌，开放性非随机分为L—OHP和CPT-11两组。L—OHP组：L—OHP85mg／nl。静脉滴注2～3h，第1天，CF200mg静脉滴注2h后，5-Fu250mg静脉推注，随后5-Fu600mg／m2静脉持续滴注22h，第1、2天，每2周重复为1个周期。CPT-11组：CPT-11150mg／I／1。静脉滴注，第1天，CF、5-Fu剂量用法同上，每2周重复为1个周期。4个周期后判定疗效和毒副作用。结果L—OHP组共完成化疗220个周期，完全缓解1例，部分缓解15例，总有效率为41．0％；CPT-11组共完成化疗204个周期，完全缓解2例，部分缓解11例，总有效率为35．1％。中位疾病进展时间（MTTP）分别为5．2、5．8个月；中位生存时间分别为13．2、14．0个月；临床获益改善率分别为71．8％、78．4％。毒副作用L—OHP组以骨髓抑制及恶心、呕吐、胃肠反应和外周感觉神经异常为主，CPT-11组以骨髓抑制及延迟性腹泻为主，Ⅲ度延迟性腹泻以CPT-11组多见（P〈0．025）。结论L—OHP或CPT-11联合5-Fu治疗晚期结直肠癌疗效好，毒副作用较小，安全，患者易接受。     

Effect of pirarubicin for elderly patients with malignant lymphoma

To determine the effect of a chemotherapy regimen containing pirarubicin, a multicenter clinical trial was performed in naive patients > or = 65 years with malignant lymphoma, between January 1990 and December 1992. The total number of patients was 37 (median age 74.2 years). One of three different types of chemotherapy regimens, which was administered every 3 to 5 weeks, was chosen for each patient at random. Regimen A (THP-COP) included pirarubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1), vincristine (1 mg/m2; day 1) and prednisolone (30 mg/m2; days 1-5), regimen B, modified "CHOP", included doxorubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1) vincristine (1 mg/m2; day 1) and prednisolone (30 mg/m2; days 1-5); regimen C (THP-COPE) included etoposide (80 mg/m2; day 1) in addition to regimen A. The complete response (CR) rate was 60.0%, 45.5% and 62.5% with regimen A, B and C. The partial response (PR) rate with regimen A was 20.0%, 18.2% with B and 25.0% with C. The 50% survival period with regimen A was more than 1,000 days, with C 643 days but it was only 365 days with B. The adverse effects related to these treatments occurred more frequently in regimen B than A and C showing a statistically significant difference. We concluded that chemotherapy regimens containing pirarubicin are useful and safe for the elderly patients with malignant lymphoma.     

cis-platinum-based alternating non-cross-resistant chemotherapy as a first-line treatment in metastatic breast cancer. A phase II study

Exposure to multiple non-cross-resistant drugs should increase cell kill and the chance of achieving more complete and partial responses. Our earlier study in breast cancer showed that second-line CAP (cyclophosphamide, adriamycin, cis-platinum) treatment was not cross-resistant to the CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone) regimen and produced a 51% response rate. These facts initiated a phase II study which used an alternating CMFVP/CAP regimen. Altogether, 49 patients entered the study and 45 were evaluated (greater than 2 cycles). The CMFVP regimen consisted of cyclophosphamide (200 mg/m2 on days 1, 2, 3, 4 and 5), methotrexate (30 mg/m2 on days 2 and 4), 5-fluorouracil (500 mg/m2 on days 1, 3 and 5), vincristine (1.4 mg/m2 on days 1 and 5), and prednisolone (40 mg p.o. on days 1-5), and was alternated with the CAP schedule (300 mg/m2 cyclophosphamide on days 1, 3 and 5, 50 mg/m2 adriamycin on day 1, and 30 mg/m2 cis-platinum on days 1, 3 and 5). Overall response was high, and 37 patients out of 45 responded (82%), with a 28% CR rate (13/45). A particularly high response rate was observed in soft tissues (86%, 18/21) and visceral organs (84%, 16/19). Only 1 patient progressed (3%). The duration of remission was 4-21+ months (median, 12 months). Six of 13 CR patients were still disease free 15 months after the treatment was stopped. The duration of survival was 5-25+ months (median, 15+ months). Toxicity was moderate (myelosuppression in 53% of patients, mainly grade I-II; stomatitis in 11%, except for 100% alopecia and 90% nausea and vomiting). One drug-related death (bone marrow aplasia) was recorded. The high antitumorigenic activity of the alternating regimen used is encouraging and may call for a randomized study for the ultimate evaluation of this treatment approach.     

Chemotherapy of small-cell carcinoma of lung: a randomized comparison of alternating and sequential combination chemotherapy programs

One hundred forty-seven eligible patients with small-cell carcinoma of the lung (SCCL) have been randomized to receive alternating (A) or sequential (S) combination chemotherapy. Initial treatment was with three cycles of VAM (A) or two cycles of POCC (S). VAM consists of VP16-213 200 mg/m2 intravenously (IV) day 1, Adriamycin (Adria Laboratories, Columbus, Ohio) 50 mg/m2 IV day 1, and methotrexate 30 mg/m2 IV day 1 repeated at 21-day intervals. POCC consists of cyclophosphamide 600 mg/m2 IV days 1 and 8, vincristine 1.5 mg/m2 (maximum, 2 mg) IV days 1 and 8, CCNU 60 mg/m2 po day 1, and procarbazine 100 mg/m2 po days 2 through 15. After initial treatment, all patients received whole brain radiation therapy (3,000 rad/10 fractions/2 wk). Patients with limited disease in addition received irradiation encompassing the tumor, hilar, mediastinal, and supraclavicular regions (5,000 rad/25 fractions/5 wk). After radiation, patients on arm A received POCC alternating with VAM; patients on arm S received POCC until progression when they were to be treated with VAM. The alternating arm was superior with respect to rate of complete remission (CR), median disease-free survival (MDFS), and median survival (MS). The advantage of alternating therapy was not as clearly demonstrated in the limited disease groups when interposition of involved field radiation delayed the initiation of the alternating schedule. In limited disease alone, comparing arm A with arm S, no statistically significant differences were noted. The CR rate was 42% v 54%, MDFS was 14 v 10 months, and MS was 16 v 10 months. In extensive disease, the CR rate was 44% v 20% (P = .03), MDFS was 6 v 4 months (P = .003), and MS was 10 v 7 months (P = .001). Improved treatment outcome in SCCL is achieved when combination chemotherapy regimens of similar effectiveness are administered in an alternating rather than sequential schedule.     

奥沙利铂联合亚叶酸钙及5-氟尿嘧啶治疗晚期大肠癌的临床观察

目的观察奥沙利铂(L-OHP)联合亚叶酸钙(CF)及5-氟尿嘧啶(5-Fu)治疗晚期大肠癌的疗效及不良反应。方法将我院2002年10月~2005年10月收治的65例晚期大肠癌,随机分为A组和B组,A组奥沙利铂130mg/m2静脉滴注2小时,第1天;亚叶酸钙200mg/m2持续静滴24小时,第1~5天;5-氟尿嘧啶500mg/m2持续静滴24小时,第1~5天;每3周重复。B组羟基喜树碱(HCPT)8mg/m2静脉滴注,第1~5天;亚叶酸钙200mg/m2,静脉滴注2小时,第1~5天;5-氟尿嘧啶500mg/m2持续静滴24小时,第1~5天,每3周重复。所有病例均接受2周期化疗。结果A组CR2例,PR12例,SD11例,DD8例,总有效率42.4%,B组CR1例,PR5例,SD16例,PD10例,总有效率18.8%,A组的主要不良反应是周围神经炎及恶心呕吐、骨髓抑制。结论奥沙利铂联合亚叶酸钙及5-氟尿嘧啶疗效优于羟基喜树碱、亚叶酸钙、5-氟尿嘧啶联合化疗,不良反应轻,值得临床推广。     

吉西他滨联合卡培他滨治疗晚期三阴性乳腺癌的临床观察

目的观察吉西他滨联合卡培他滨治疗ER、PR、HER-2均阴性（三阴性）晚期转移性乳腺癌的疗效与安全性。方法 2004年7月至2009年6月共14例经免疫组化证实ER、PR、HER-2均阴性的晚期转移性乳腺癌复治患者参与研究。患者接受吉西他滨联合卡培他滨方案治疗：吉西他滨800mg/m2,静脉滴注30min,d1、d8、d15;卡培他滨2500mg/m2口服,d1～14。28d重复。结果全组14例共完成58个周期的治疗,中位数4个周期,范围2～6个周期,均可评价疗效。完全缓解0例,部分缓解4例（28.6%）,病情稳定6例（42.9%）,病情进展4例（28.6%）,客观有效率为28.6%;中位疾病进展时间（mTTP）6个月（95%CI：2～10个月）,中位生存期（OS）16个月（95%CI：6～32个月）,1年生存率为64.4%,3年生存率为14.3%。毒副反应主要为Ⅰ～Ⅲ度骨髓抑制、胃肠道反应、手足综合征、末梢神经毒性、流感样症状、轻度肝功能损伤等。结论吉西他滨联合卡培他滨治疗晚期三阴性乳腺癌患者,初步观察有一定的疗效,其毒副作用患者可以耐受。     

多西紫杉醇腹腔灌注化疗治疗晚期胃癌Ⅱ期临床研究

目的:探讨多西紫杉醇(DOC)腹腔灌注化疗(intraperitoneal chemotherapy,IPC)联合亚叶酸钙(CF)/5-氟尿嘧啶(5-FU)/奥沙利铂(OXA)静脉用药治疗晚期胃癌的临床疗效和安全性。方法:2007年7月至2009年9月,给与43例TNMⅢb-Ⅳ期胃癌患者(Ⅲb期19例,Ⅳ24期例)DOC 40mg/m2腹腔灌注d1,8,CF200mg/m2静脉滴注d1-5,5-FU 375mg/m2静脉滴注d1-5,OXA 135mg/m2静脉滴注d1方案,每21天为一周期,共2-4个周期,每2周期评价疗效。结果:总有效率(CR+PR)为58.1%(25/43),其中CR6.9%(3/43)、PR51.2%(22/43)。中位疾病进展时间(mTTP)为7.5(2.3-14.2)个月。一年生存率为67.4%。常见不良反应为腹痛、腹泻、骨髓抑制、胃肠道反应、脱发、口腔黏膜炎和外周神经毒性等。结论:DOC 40mg/m2腹腔灌注d1,8,联合CF/5-FU/OXA方案静脉用药治疗晚期胃癌疗效肯定,且不良反应可以耐受。     

Comparative trial of cytarabine and thioguanine in combination with amsacrine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol

Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara-C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted.     

紫杉醇脂质体联合奈达铂同步放疗在中晚期宫颈癌中的临床研究

目的 比较紫杉醇脂质体联合奈达铂同步放疗与氟尿嘧啶联合奈达铂同步放疗治疗中晚期宫颈癌的疗效和不良反应。方法 回顾性分析2010年5月至2012年5月收治的中晚期宫颈癌患者58例,分为紫杉醇脂质体联合奈达铂组（A组,n=30）和氟尿嘧啶联合奈达铂组（B组,n=28）。两组同步放疗均为盆腔三维适形放疗加后装放疗,保证A点总剂量70～85Gy,B点总剂量50Gy。两组患者在放疗第1天同步进行化疗。A组：紫杉醇脂质体135mg/m2静滴,d1;奈达铂80mg/m2静滴,d1;B组：氟尿嘧啶500mg/m2静滴,d1～d5;奈达铂80mg/m2静滴,d1。两组化疗均21～28天为1周期,化疗2个周期。结果全部患者均按计划完成治疗。A组的有效率为76.7%（CR 13例,PR 10例,SD 6例,PD 1例）,B组为57.1%（CR 9例,PR 7例,SD 7例,PD 5例）,两组差异有统计学意义（P＜0. 05）。A组1、2年生存率分别为100%和92%,B组分别为88%和75%,两组差异有统计学意义（P＜0.05）。两组不良反应主要为骨髓抑制和消化道反应,A组的不良反应发生率低于B组,差异有统计学意义（P＜0.05）。结论 紫杉醇脂质体联合奈达铂同步放疗治疗中晚期宫颈癌疗效确切,不良反应轻,值得临床推广应用。     

多西紫杉醇联合5-氟尿嘧啶、亚叶酸钙及草酸铂治疗胃癌肝转移的临床观察

 目的 观察多西紫杉醇联合5-氟尿嘧啶、亚叶酸钙及草酸铂治疗胃癌肝转移的疗效及毒副反应。方法 多西紫杉醇50mg/m^2,d1,草酸铂100mg/m²,d1,5-Fu750mg/（m².d）持续静脉滴注48h,d1～2,CF200mg,d1～3,每2周重复。完成3周期后评价疗效。结果 全组24例患者,治疗后CR2例,PR12例,RR（CR＋PR）为58.3%。中位生存时间（MST）11.2个月,中位疾病进展时间（TTP）6.6个月。主要不良反应为骨髓抑制、神经毒性、粘膜炎等。结论 多西紫杉醇联合5-氟尿嘧啶、亚叶酸钙及草酸铂治疗胃癌肝转移有效率较高,可提高患者的生存质量,毒副作用能耐受。     

Randomized phase II study comparing topotecan/cisplatin administration for 5 days versus 3 days in the treatment of extensive stage small cell lung cancer (SCLC)

BACKGROUND: Topotecan (T) is an active drug in SCLC. A combination of topotecan with cisplatin (DDP) was suggested to be highly synergistic. This phase II trial was initiated to assess the activity of T/DDP in chemotherapy-naive patients suffering from extensive disease small cell lung cancer (SCLC) and to compare the conventional 5-day regime with an experimental 3-day schedule. PATIENTS AND METHODS: A total of 86 patients were included. Patients were randomized to receive either T 1.0 mg/m2 d 1-5 and DDP 75 mg/m2 d 5 (arm A) or T 1.5 mg/m2 d 1-3 and DDP 75 mg/m2 d 3 (arm B). Six cycles were given at a 3-week interval. RESULTS: Data of 84 evaluable patients (67 males and 17 females) were analysed. All patients had metastatic disease. The best response rate was 61.9% in arm A and 59.5% in arm B. Median overall survival was 8.7 months in arm A and 7.6 months in arm B (p=0.6809). CONCLUSIONS: Combination of T and DDP is active in ED SCLC. Toxicity and median survival were comparable in both arms. Three days treatment seems to be similar to the 5 days regime.