Combination chemotherapy of ifosfamide, cisplatin and vindesine for non-small cell lung cancer

Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 1 & 8, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.     

Combination chemotherapy with mitomycin C, methotrexate, cisplatin, and vinblastine in the treatment of non-small cell lung cancer

The combination of mitomycin C, methotrexate, cisplatin, and vinblastine was administered to 45 patients with unresectable non-small cell lung cancer. Thirty-nine patients satisfied criteria for assessment of response to chemotherapy. All patients had a performance status of greater than 50%, had evaluable disease, and had not received previous chemotherapy. The overall response rate was 54% with responses seen in 12 of 19 squamous cell, 8 of 16 adenocarcinoma, and 1 of 4 undifferentiated large cell lung cancer patients. Median survival was increased by 3 months in those patients with an objective response to chemotherapy. Drug-associated toxicity was rare, but apparent mitomycin C-related pulmonary fibrosis was observed in two patients. This four-drug combination was shown to be an active regimen in the treatment of non-small cell bronchogenic carcinoma.     

A randomized trial comparing vindesine plus cisplatin with mitomycin C, vindesine plus cisplatin in patients with advanced non-small cell lung cancer

Thirty-six evaluable patients with advanced non-small cell lung cancer were randomized to treatments involving vindesine (3 mg/m2 X 3) plus cisplatin (80-120 mg/m2) versus mitomycin C (8 mg/m2) plus vindesine (2 mg/m2 X 3) plus cisplatin (80-120 mg/m2). The response rate for the vindesine and cisplatin combination was 29%, versus 47% for the mitomycin C, vindesine and cisplatin combination. There was no evidence of improved duration of response in patients given mitomycin C, vindesine and cisplatin. The median survival for patients given mitomycin C, vindesine and cisplatin was 11.4 months, compared with 10.3 months for those given vindesine and cisplatin. Toxicity was almost comparable for the two treatments. The utility of addition of mitomycin C to vindesine and cisplatin should be evaluated in further investigations.     

Combination chemotherapy with S-1 and cisplatin for non-small cell lung cancer

S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4-dihydroxypyridine and potassium oxonate to strengthen biological activities of 5-fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus cisplatin (CDDP) was reported to be 47%, and the median survival time was 11 months. Adverse events of the combination chemotherapy were milder than other combination chemotherapy described before. Therefore, S-1 plus CDDP combination chemotherapy is a future candidate for phase III clinical study.     

Clinical study of combination chemotherapy with mitomycin C, vindesine and cisplatin (MVP therapy) in advanced non-small cell lung cancer

Thirty-seven patients with inoperable non-small cell lung cancer were treated with the combination chemotherapy (MVP therapy) with mitomycin C (8 mg/m2), vindesine (3 mg/m2 X 2) and cisplatin (60 mg/m2). The partial responders were 13 cases (35%), and the median survival time was 271 days. In this study the cisplatin dose was less than in any other report of "MVP" therapy. But both the response rate and the median survival time did not differ from those reported elsewhere. The side effects (bone marrow suppression, renal toxicity, etc.) were mild, and did not prevent the continuance of this therapy. Thus, we could repeat more than 6 courses of "MVP" therapy for 8 patients. Nowadays, it is difficult to obtain complete responders with any chemotherapy for inoperable non-small cell lung cancer. To prolong lives of patients and maintain good quality of life, we recommend chemotherapy with low toxicity in often-repeatable courses.     

丝裂霉素、异环磷酰胺和顺铂治疗晚期非小细胞肺癌

目的 观察丝裂霉素、异环磷酰胺和顺铂组成的ＭＩＰ方案治疗晚期非小细胞肺癌的近期疗效,耐受性和生存期。方法 ５６例晚期非小细胞肺癌接受ＭＩＰ方案治疗。结果 可评价疗效病例５６例,总有效率４６．４％,中位缓解期８个月,中位生存期９．６个月,１年生存率３５．０％。主要毒副作用为骨髓抑制。;结论 ＭＩＰ联合化疗方案对晚期非小细胞肺癌有较好疗效,毒副作用可耐受。     

健择、顺铂联合治疗Ⅲ和Ⅳ期非小细胞肺癌

目的　观察健择与顺铂联合化疗方案治疗非小细胞肺癌(NSCLC)的临床疗效和毒性反应。方法　12例入选者均为Ⅲ期(41.7%)和Ⅳ期(58.3%)NSCLC患者,且未接受过其它化疗和放疗。28天为一疗程,第1、8、15天静脉滴注健择1000mg/m2,第1天加用顺铂100mg/m2。结果　11例可评价患者中6例(54.5%)获部分缓解,总有效率为54.5%。主要的副反应是血液学毒性,WHOCTC的Ⅲ、Ⅳ度中性粒细胞减少发生率为33.3%(4/12),Ⅲ、Ⅳ度血小板减少的发生率为41.7%(5/12)。非血液学毒性皆轻度并可耐受。因毒性反应减少健择用量和停药比率为15.2%。经随访,3例存活,8例死亡。中位存活8个月。结论　健择与顺铂联合化疗方案治疗NSCLC有较好疗效。患者临床症状及生活质量明显改善,且有较好的耐受性,该治疗尤其适合老年患者。     

MVP和TVP治疗晚期非小细胞肺癌的前瞻随机研究

目的 评价MVP和TVP两种方案治疗晚期非小细胞肺癌的有效率、毒性和生存期。方法 66例晚期非小细胞肺痛随机分为两组，MVP组32例，TVP组34例，两组患者资料相似。MVP组：丝裂霉素(MMC)6～8mg／m^2，静注，第1天；长春花碱酰胺(VDS)2～3mg／m^2，静滴，第1、8天；顺铂(DDP)70～80mg／m^2，静滴，第1天或分两天。TVP组：吡喃阿霉素(THP)40～50mg／m^2，第1天，VDS和DDP同上。两方案均为一周期21天，每例完成2～4周期。结果 MVP组有效率为34％(完全缓解1例，部分缓解10例)，TVP组有效率为56％(完全缓解1例，部分缓解18例)，TVP有效率高于MVP组，但统计学无意义(X^2=2．269，P=0．132)。TVP组Ⅲ Ⅳ度骨髓抑制发生率高于MVP组，其中粒细胞抑制有显著性差异(79％与44％，X^2=7．458，P=0．006)。MVP组与TVP组的中位生存期分别为12个月与8个月，1年生存率53％与24％(X^2=4．943，P=0．026)，2年生存率17％与6％，3年生存率6％与0。结论 MVP有效率相对较低，但血液毒性低，患者生存期和牛存率高，是晚期非小细胞肺癌化疗的合适方案。TVP方案近期有效率高，但血液毒性明显，与MVP方案比较，没有明显的生存受益。     

Combination chemotherapy without cisplatin in the treatment of advanced non-small cell lung cancer

Cisplatin-based combinations are standard regimens in the treatment of advanced non-small cell lung cancer. Survival improvement has been achieved using this therapy. However, the high toxicity induced by cisplatin-based doublets urges the research of alternate treatments. Newest cytotoxic compounds yield a better efficacy-toxicity ratio. Platinum-free doublet regimens based on new drugs are expected to offer the patient an improved survival without decreasing his quality of life. Treatment-allocated time and period with high grade toxicity could be considered as wasted from the patient point of view. QUALY methods based on time without symptoms and toxicity allow the accurate evaluation of this end-point. This brief state-of-the-art deals with methodological statements highlighted by the first publications of randomized studies comparing non-platinum-based doublets with either single-drug chemotherapy or standard cisplatin-based doublets.     

A randomized trial in inoperable non-small-cell lung cancer: vindesine and cisplatin versus mitomycin, vindesine, and cisplatin versus etoposide and cisplatin alternating with vindesine and mitomycin.

Patients with inoperable non-small-cell lung cancer (NSCLC) were randomly assigned to receive one of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine, and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). In 199 assessable patients, the response rates were VP, 33%; MVP, 43%; and EP/VM, 19%. The addition of mitomycin to the VP regimen did not significantly improve the response rate. The response rate was significantly lower with the EP/VM regimen than with the MVP regimen (P less than .01). The median survival times were VP, 50 weeks; MVP, 42 weeks; and EP/VM, 40 weeks. These differences were not significant. Grade III or IV thrombocytopenia was significantly greater (P less than .01) in MVP patients (22%) than in the VP (5%). Other toxicities were similar in the three groups. Analyses of prognostic factors showed that treatment with MVP, sex, and histologic classification (squamous cell carcinoma) were predictive of improved response. Important factors for improved survival, according to the Cox regression analysis, were the stage of disease, performance status, sex, weight loss before diagnosis, and hemoglobin concentration.     

诺维本联合顺铂治疗NSCLC 90例临床观察

目的 评价诺维本（ｎａｖｅｌｂｉｎｅ,ＮＶＢ）与顺铂（ｃｉｓｐｌａｔｉｎ,ＤＤＰ）联合治疗非小细胞肺癌（ｎｏｎ－ｓｍａｌｌ ｃｅｌｌ ｌｕｎｇ ｃａｎｃｅｒ,ＮＳＣＬＣ）的疗铲及毒副反应。方法 自１９９４年４月至１９９８年１２月对９０例中晚期ＮＳＣＬＣ患者进行ＮＶＢ＋ＤＤＰ联合化疗,第１、８天用ＮＶＢ２５～３０ｍｇ／ｍ＾２,第３天用ＤＤＰ６０～８０ｍｇ／ｍ＾２,每２８天为一周期,每例患者至少完成２     

Combination chemotherapy with etoposide, mitomycin C, and cyclophosphamide in advanced non-small cell lung cancer

Forty-three patients with advanced non-small cell lung cancer were treated with a combination chemotherapy regimen comprising etoposide 100 mg/m2 p.o. days 1-5, mitomycin C 10 mg/m2 i.v. day 1 and cyclophosphamide 500 mg/m2 i.v. day 1, every 4 weeks. The median age was 61, and the median initial PS-2. Fourteen patients had received prior therapy. The response rates in previously untreated patients were 25% (5/20) for adenocarcinoma, 0% (0/4) for squamous cell carcinoma, 0% (0/3) for large cell carcinoma, and 18.5% (5/27) for all patients. There were no responders among the pretreated patients. The median survival time was 7 months for previously untreated patients, 4 months for pretreated patients and 6 months for all patients. Patients with adenocarcinoma survived significantly longer (8 months) than those with squamous cell carcinoma (4 months) and large cell carcinoma (3 months). Toxicity consisted of leukopenia (74%), anemia (74%), nausea or vomiting (55%) and alopecia (94%).     

长春瑞宾联合顺铂治疗进展期非小细胞肺癌50例临床观察

目的观察长春瑞宾联合顺铂治疗进展期非小细胞肺癌的疗效及毒副反应。方法长春瑞宾25mg／m^2d1,8，静脉滴注，顺铂25mg／m^2，d1～3，静脉滴注，21天为1周期，至少两周期以上评价疗效。结果50例可评价疗效的患者中，完全缓解（CR）2例，部分缓解（PR）19例，总有效率为42．0%（21／50），疗效分析显示Ⅲb期有效率为44．8％，Ⅳ期有效率为38．1％（x^2=0．227，P=0．634）。50例患者中位生存期（MST）10．0个月，其中Ⅲb期MST13．6个月，Ⅳ期MST8．6个月（X^2=0．239，P=0．601）。50例患者1年生存率42．0%，其中Ⅲb44．8％（13／29），Ⅳ期38．1％（8／21）（X^2=0．245，P=0．596）。主要毒副反应为骨髓抑制和消化道反应，白细胞减少为76.0％（Ⅱ～Ⅳ级为28．0％），血小板减少为42．0%（Ⅲ～Ⅳ级为2．0％），消化道反应为72．0％（Ⅲ～Ⅳ级为12．0％），静脉炎为48．0％（Ⅲ～Ⅳ级为6．0%），脱发为46．0％（Ⅲ～Ⅳ级为6．0%）。结论长春瑞宾联合顺铂治疗进展期非小细胞肺癌为有效的一线联合化疗方案。     

Lung toxicity of trimodality chemoradiotherapy with mitomycin C, vindesine, and cisplatin followed by surgery for locally advanced non-small cell lung cancer

To evaluate lung toxicity of mitomycin C containing chemotherapy regimen combined with thoracic radiotherapy, a retrospective study was carried out in patients with locally advanced non-small cell lung cancer who were enrolled in a randomized trial for chemoradiotherapy. Postoperative complications and pathological pulmonary toxicity were investigated in 7 surgical patients out of 306 enrolled patients who were treated with MVP combination chemotherapy and concurrent or sequential thoracic radiotherapy of 56 Gy. The 7 patients were 45-66 years old (median 50 years old), with 4 of stage IIIA, 3 of stage IIIB, 4 with adenocarcinoma, 2 with squamous cell carcinoma, and 1 with large cell carcinoma. Five patients were treated with 2 cycles and 2 with 3 cycles. Anti-tumor response was observed to be PR in 6 cases and NC in 1 case. In the chemoradiotherapy, pulmonary toxicity was observed at grade 1 in only 1 case. Postoperative complications consisted of a ruptured suture, chylothorax and empyema which were treated and healed in the 3 cases respectively. Pathological examination of the resected lung was performed in 6 cases, with revealed alveolitis in 3 cases and fibrosis in all cases in the radiation field. Three cases, however, showed slight alveolitis outside of the radiation field. In conclusion, as severe lung toxicity was not observed in the surgical cases after chemoradiotherapy including MMC, there appears to be no reason to exclude MMC from regimens for trimodality combination therapy.     

Combination chemotherapy with topotecan for non-small cell lung cancer

Patients with non-small cell lung cancer (NSCLC) typically receive platinum-based combination chemotherapy. In spite of improvements in symptoms and survival, response rates remain low and newer agents are being investigated. The newer agents may offer increased efficacy and reduced toxicity compared with established agents and regimens. The topoisomerase-I inhibitor, topotecan, achieves single-agent response rates of 4-25% in NSCLC. Topotecan has also been studied in combinations: a combination of topotecan, administered using the standard 5-day schedule, with cisplatin was effective but was associated with myelosuppression. The combination of topotecan plus carboplatin may be better tolerated and warrants further investigation. Topotecan was also combined with newer agents (gemcitabine, vinorelbine, docetaxel, paclitaxel) using a range of different administration schedules of topotecan. Response rates of up to 30% were achieved. A weekly schedule of topotecan was effective and well tolerated and was also convenient for healthcare professionals and patients.     

A four-drug combination chemotherapy with cisplatin, mitomycin, vindesine and 5-fluorouracil: A regimen associated with major toxicity in patients with advanced non-small cell lung cancer

PURPOSE:: To determine in patients with advanced non-small cell lung cancerthe activity of a 4-drug combination chemotherapy. PATIENTS AND METHODS:: Chemotherapy consisted of the administration of cisplatin (30mg/m² d 1–3 or 4), mitomycin C (10 mg/m² d 1), vindesine(3 mg/m² d 1) and 5-FU (1 g/m² d 1–3 or 4 by continuousintravenous infusion. RESULTS:: 182 were eligible patients. A 34% objective response rate wasobserved in the 164 evaluable patients. The overall median survivalwas 26 weeks. The most serious adverse event was the occurrenceof 18 (10%) cardiac or sudden deaths. These toxic deaths weresignificantly associated with a 5% loss of body weight priorto therapy. CONCLUSIONS:: The regimen studied resulted in a very significant cardiac toxicity. cardiac toxicity, chemotherapy, non-small cell lung cancer     

MVP方案治疗晚期乳腺癌的疗效观察

目的 观察MVP(MMC、VDS、DDP)方案对复发转移的晚期乳腺癌的治疗效果。方法 45例晚期乳腺癌采用MVP方案治疗，MMC6～8mg／m^2，静注，第1天；VDS2．5～3mg／m^2，静注，第1，8天；DDP30mg／m^2静滴，第1～3天，每3周重复。结果 总有效率46．7％，其中CR11．1％，PR35．6％。不良反应主要为胃肠道反应、骨髓抑制、脱发、静脉炎和神经毒性，病人均能耐受。结论 MVP方案对治疗复发转移的晚期乳腺癌有效，毒副反应可耐受，可作为晚期乳腺癌解救治疗方案之一。     

A pilot study of mitomycin, ifosfamide and cisplatin as outpatient combination chemotherapy for advanced non-small cell lung cancer.

Twenty-one patients with advanced stage, non-small-cell lung carcinoma were treated with a chemotherapy regimen including: mitomycin (6 mg/m2), ifosfamide (3 g/m2), cisplatin (80 mg/m2). The regimen was administered on an outpatient basis. Two patients were lost to follow-up. Among the 29 patients evaluable for response we registered a response rate of 36.8%; 36.8% of patients had stable disease, and 15.7% progressed during treatment. Median duration was 8.7 months and median survival was 11 months. Toxicity was low and easily manageable on an out-patient basis.