Phase II study of vindesine, cisplatin, and hexamethylmelamine (VCH) in small cell carcinoma of the lung

Forty-two patients with small cell carcinoma of the lung were treated with cycles given every 28 days consisting of a combination of vindesine (3 mg/m2 if on Days 1 and 15), cisplatin (75 mg/m2 iv on Day 1), and hexamethylmelamine (200 mg/m2 orally on Days 8-22). Thirty-four patients were evaluable for response. Partial remission (PR) or complete remission (CR) was noted in seven (three CRs and four PRs) of nine previously untreated patients (77%) and in eight (one CR and seven PRs) of 25 patients treated previously with intensive chemotherapy (32%). This drug combination deserves consideration for inclusion in sequential combination chemotherapy regimens.     

紫杉醇+顺铂二线治疗小细胞肺癌38例临床观察

目的 研究紫杉醇+顺铂二线治疗复治小细胞肺癌患者的疗效和毒副反应.方法 纳入一线含铂方案(依托泊苷+卡铂)化疗失败患者38例,采用紫杉醇135 mg/m2,第1天;顺铂70 mg/m2,第1～3天,每3～4周为1个周期,连用2～4个周期.结果 部分缓解12例,稳定14例,进展12例,总有效率31.6％(12/38),疾病控制率68.4％(26/38),总生存期10.5个月,中位生存期6.8个月.化疗敏感者有效率39.3％(11/28);化疗耐药者有效率10.0％(1/10).本组38例均可评价毒副反应,Ⅲ度以上白细胞及中性粒细胞减少分别为47.4％(18/38)、57.9％(22/38).Ⅳ度中性粒细胞减少15.8％(6/38).中性粒细胞减少性发热10.5％(4/38).主要非血液学毒副反应是乏力、恶心呕吐、周围神经毒性,Ⅲ度以上毒性反应是乏力55.3％(21/38)、恶心呕吐31.6％(12/38).结论 紫杉醇+顺铂治疗复治小细胞肺癌有效且毒副反应可耐受.     

复发性小细胞肺癌的治疗策略及进展

小细胞肺癌是一种对放、化疗敏感,但易复发的实体性肿瘤.对于身体状况许可的小细胞肺癌复发患者,应接受二线化疗;若一线治疗无效或无疾病进展时间小于3个月,应选择与一线化疗非交叉耐药的二线化疗;若一线治疗有效且无疾病进展时间大于3个月,拓扑替康是首选;若无疾病进展时间超过6个月,则可继续原方案治疗;若出现有症状的脑和骨转移、胸腔内复发和(或)出现大气道阻塞、上腔静脉阻塞综合征的患者,可考虑放疗或放、化疗结合.针对小细胞肺癌的生物靶向治疗有待进一步研究.     

Phase II trial of cisplatin in small cell carcinoma of the lung

Eighteen patients with histologically documented small cell carcinoma of the lung who had failed initial combination chemotherapy regimens were treated with single-agent cisplatin in a dose of 100 mg/m2 every 3 weeks, with mannitol and fluid diuresis. Tumor regression was limited to one partial response (response rate, 6%; 95% confidence limits. 1%-27%). Significant toxic effects were gastrointestinal (severe nausea and vomiting in 12 of 14 patients) and hematologic (severe leukopenia in one patient and severe thrombocytopenia in three). The antitumor efficacy of high-dose cisplatin in heavily pretreated patients with small cell carcinoma of the lung appears to be marginal.     

Comparison of vindesine plus cisplatin or vindesine plus mitomycin in the treatment of advanced non-small cell lung cancer

Fifty-eight patients with advanced non-small cell lung cancer were randomly allocated to receive vindesine (3 mg/m2 every week) plus either cisplatin (80 mg/m2 every 3 weeks) or mitomycin (8 mg/m2 weekly X 3, then every 3 weeks). No patients achieved complete response. Among the 28 patients treated with vindesine plus cisplatin, there were 12 partial responders (42.9%); among the 30 patients treated with vindesine plus mitomycin, there were only three partial responders (10%) (P less than 0.005). The median duration of response was 11.5 weeks (range, 4-25) in the patients treated with vindesine plus cisplatin. The median survival times for patients treated with vindesine plus cisplatin and vindesine plus mitomycin were 10.1 and 10.2 months, respectively; there was no statistical difference in survival time between the two groups. Initial performance status was the strong predictor of patient survival. Toxic effects, including moderate myelosuppression, nephrotoxicity, peripheral neuropathy, and gastrointestinal symptoms, were generally manageable. The combination of vindesine and cisplatin appears to be effective against advanced non-small cell lung cancer.     

Combination chemotherapy with cisplatin, etoposide, and vindesine in non-small cell lung carcinoma: a clinical trial of the EORTC lung cancer working party

A combination of cisplatin (60 mg/m2 on Day 1), etoposide (120 mg/m2 on Days 3, 5, and 7), and vindesine (1.5 mg/m2 on Days 1 and 7), repeated every 3 weeks, was administered to 73 patients with non-small cell bronchogenic carcinoma. After two full courses, the results could be evaluated in 62 patients, 25 (40.3%) of whom responded (five complete responses, 20 partial responses). The median survival for the responding patients (12 months) was significantly superior (P = 0.02) to that of the nonresponding patients. There were three early toxic deaths from sepsis associated with granulocytopenia, and seven patients presented peripheral neuropathy. Although active in non-small cell bronchogenic carcinoma, the combination of cisplatin, etoposide, and vindesine does not appear to be superior to cisplatin-etoposide or cisplatin-vindesine when our previous experience and the results reported from other institutions are considered.     

A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer

Abstract A randomized trial of chemotherapy in 105 patients with advanced and metastatic nonsmall-cell lung cancer (NCSLC) was conducted in order to compare the effect of the additional drug mitomycin C (PVM) or ifosfamide (PVI), to the combination of cisplatin plus vindesine (PV). An objective response rate was observed in 42.8% of the patients treated with PVM, 42.4% with PVI and 28.6% with PV and these response rates were not statistically significant (P > 0.20). No patient achieved the complete response with either of the three regimens. Comparison of the median response durations among the three regimens showed an advantage of PVI over PVM (P < 0.02) and PV (P < 0.05). The median survival times (MST) were similar for all three regimens (PVM, 33.5; PVI, 40.0 and PV, 36.5 weeks); moreover, the difference in survival time between the three regimens of responders was not statistically significant. The univariate analysis showed that significant predictors of survival were performance status (PS) zero (P = 0.0002), limited disease (P = 0.004), no previous weight loss (P = 0.01) and normal serum albumin (P = 0.016), and in multivariate analysis by a stepwise Cox proportional hazard model, these were PS zero (a hazard ratio of 2.3, P = 0.0001) and limited disease (a hazard ratio of 1.9, P = 0.048). Toxicity did not differ among the three treatment regimens.     

Lack of efficacy of vinblastine and cisplatin in patients with progressive small cell carcinoma of the lung

Twenty patients with small cell carcinoma of the lung resistant to primary therapy, or relapsing after an objective response to initial treatment, were treated with vinblastine plus high-dose cisplatin chemotherapy. One patient achieved a partial remission lasting 4 months, while 19 patients had no objective response to this regimen. The median survival from the time of disease progression to death was 2.5 months (range, 1-7), with an overall median survival of 13 months (range, 5-31; diagnosis to death). In our patients, vinblastine plus cisplatin given as salvage therapy did not produce a significant response rate or survival prolongation.     

Trial of the combination of mitomycin, vindesine, and cisplatin in patients with advanced non-small cell lung cancer

In prior trials, mitomycin, vindesine, and cisplatin have each been shown to have reproducible antitumor activity as single agents when used in the treatment of patients with non-small cell lung cancer. The two-drug combinations of vindesine plus high-dose cisplatin or mitomycin have shown an improved major response rate and manageable toxicity in prior trials. In this report, 90 patients with stage III non-small cell lung cancer were treated with the three-drug combination of mitomycin (8 mg/m2), vindesine (3 mg/m2), and high-dose cisplatin (120 mg/m2). Eighty-seven patients (97%) were adequate for both response and toxicity. Major objective responses occurred in 60% of the patients. The toxicity of this regimen was predictable and manageable when established supportive care measures were employed. Based on the response rate observed, the combination of these three agents merits further study in randomized trials against other chemotherapeutic regimens and consideration of its use in adjuvant and preoperative settings.     

Phase II evaluation of vindesine in patients with non-small cell carcinoma of the lung.

Fifty-two patients with non-small cell carcinoma of the lung were treated iv with doses of vindesine at 3--4 mg/m2/week iv. Partial responses occurred in all histologic types in ten of 46 adequately treated patients, for an overall response rate of 22%. Patients not previously treated with chemotherapy had a higher response rate than those who had received prior chemotherapy (33% versus 12%). Reversible peripheral neuropathy occurred in all patients, and was generally of a mild to moderate degree. Mild leukopenia was seen frequently, with a median wbc nadir of 2900/mm3. As reported with the older vinca alkaloids, platelet-sparing with occasional episodes of thrombocytosis occurred with vindesine. It is concluded that vindesine is an active agent in non-small cell carcinoma of the lung and that further studies in previously untreated patients are indicated.     

Etoposide and cisplatin salvage chemotherapy for small cell lung cancer

Thirty patients with previously treated small cell lung cancer received salvage combination chemotherapy with etoposide and cisplatin. Two complete and six partial responses were observed, for a major response rate of 27%. Responses occurred promptly and sustained palliation was achieved among responders. Myelosuppression was the major dose-limiting toxic effect. A schedule of etoposide (115 mg/m2 iv on Days 1-3) and cisplatin (25 mg/m2 iv on Days 1-3 every 28 days) is recommended for further clinical trials.     

Combined chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy in inoperable nonmetastatic squamous cell carcinoma of the lung

Thirty-three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a phase II study combining chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy. Fourteen patients had an objective response rate of 42% (two complete responses and 12 partial responses) with the first two cycles of chemotherapy. All patients received radiation therapy to the primary tumor, mediastinum, and supraclavicular nodes, and responders to chemotherapy received four additional cycles. On final evaluation, 18 patients (54.5%) achieved complete response and six patients (18%) achieved partial response. The objective response rate was 73% with the combined therapy. The median survival was 15.9 months. Toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.     

Esophageal small cell carcinoma effectively treated by cisplatin and irinotecan

Small cell carcinoma of the esophagus (SSCE) is regarded as a relatively uncommon neoplasm. Because of its aggressive characteristics with early systemic dissemination and widespread metastasis, SCCE is often associated with a poor prognosis. We report a case of carcinoembryonic antigen-positive SCCE coexistent with squamous cell carcinoma, which was successfully treated with cisplatin (CDDP) and irinotecan (CPT-11). The present case showed no evidence of distant metastasis at the time of preoperative examination. Therefore, the surgical resection was selected as a primary treatment followed by adjuvant therapy (CDDP and 5-flourouracil). However, multiple liver metastases appeared 8 months after the surgery. We changed the chemotherapy to CPT-11 and CDDP, because the regimen is effective for small cell carcinoma of the lung. After six courses of this regimen, the metastatic lesions had dramatically disappeared. These facts suggest that surgical intervention followed by a new regimen consisting of CDDP and CPT-11 is an effective treatment for SCCE.     

Randomized trial comparing vindesine plus cisplatin with vinblastine plus cisplatin in patients with non-small cell lung cancer, with an analysis of methods of response assessment

One hundred eight patients with stage III non-small cell lung cancer were randomly assigned to receive cisplatin (120 mg/m2) with either vindesine (3 mg/m2) or vinblastine (6 mg/m2). None had previously received chemotherapy. An additional goal was to determine if the observation of visible evaluable lesions was as accurate a method of response assessment as the observation of bidimensionally measurable lesions in non-small cell lung cancer. When vindesine plus cisplatin was compared to vinblastine plus cisplatin, response rates (33% vs 41%), median response durations (8.6 vs 5.6 months), and median survival times of responding patients (18.4 vs 16.2 months) were similar. Response rates, response durations, and survival times of responding patients determined through the observation of evaluable or measurable indicator lesions did not differ significantly. More patients receiving vinblastine plus cisplatin experienced wbc counts less than 2100/mm3 (P = 0.003). The two regimens demonstrated comparable response and survival data but clinically significant leukopenia was more common in vinblastine-treated patients. There was no difference in response data obtained through the study of patients with measurable and evaluable indicator lesions.     

Treatment of small cell lung cancer

Small cell lung cancer (SCLC) is a very chemo- and radiosensitive systemic disease. Combination chemotherapy produces a survival advantage resulting in median survival of 9 to 12 months in extensive disease. Platinum and etoposide in combination with concurrent, early, hyperfractionated chest radiotherapy, in patients with limited disease, produces median survival of 20 months. Prophylactic cranial radiotherapy, in patients with complete response following induction chemotherapy, reduces the incidence of brain metastases and improves survival. Triplet combinations, dose intensification, and maintenance therapy have not demonstrated meaningful survival improvements. Recurrent disease can be treated with the same chemotherapy, as in the first line treatment if the progression-free interval exceeds 3 months; otherwise, monotherapy with a novel compound is suggested. Camptothesins (topotecan, irinotecan) appear the most promising new compounds and may become first-line agents for SCLC in the near future. Molecular advances have provided many new targets for SCLC therapy. Many studies, ongoing or planned, evaluate the effectiveness of new agents developed to attack these targets.     

Combination of mitomycin, vindesine, and cisplatin in the treatment of head and neck squamous cell carcinoma

Thirty patients with squamous cell carcinoma of the head and neck were treated with a combination of mitomycin (10 mg/m2, Day 1), vindesine (3 mg/m2, Days 1 and 8), and cisplatin (60 mg/m2, Day 1), repeated every 28 days. Seven patients were previously treated by surgery, radiotherapy, or chemotherapy, and 23 had untreated advanced tumors. Objective responses were seen in 17 of 27 evaluable patients (63%), with three (11%) complete remissions. Moderate myelosuppression was the main toxic effect. Considering the advanced tumor staging (54% N3 tumors), this chemotherapeutic regimen appears as effective as other cisplatin-based chemotherapies.     

Treatment of small cell lung cancer

The incidence of small cell lung cancer (SCLC) is declining in the United States (US). SCLC is nearly universally smoking-related and is very sensitive to both chemotherapy and radiation therapy. In contrast to non-small cell lung cancer (NSCLC), SCLC is staged as either limited-stage disease (LD) or extensive-stage disease (ED). Chemotherapy remains the essential component for treatment of all patients with SCLC, regardless of stage or performance status. In LD, the addition of radiation therapy improves survival over chemotherapy alone. However, the dose, timing and schedule of radiation are not well defined. Prophylactic cranial irradiation (PCI) reduces brain relapse rates, and modestly improves survival in patients in a clinical remission. Many chemotherapy agents and combinations result in high response rates in ED SCLC; however, median survival time remains 8-10 months. Cisplatin (or carboplatin) and etoposide is the standard doublet used in the United States. One study has shown cisplatin plus irinotecan to have a survival benefit over cisplatin plus etoposide, but confirmatory studies are needed. Patients with ED frequently relapse, and relapsed/refractory SCLC has a poor prognosis. The challenge remains to identify novel therapies and molecular targets to improve survival in SCLC.