Treatment of recurrent small cell lung carcinoma with vindesine and cisplatin

Thirty-two males with recurrent small cell lung cancer after previous remission were treated with vindesine (3-4 mg/m2) plus cisplatin (60-100 mg/m2). Six patients (19%) responded to this therapy with two complete (CR) and four partial remissions. Minor responses were seen in another ten patients (32%). In patients with CR survival from start of treatment lasted 61 and 38 weeks; in patients who did not achieve CR median survival was 12 weeks. Nausea and vomiting were the predominant side effects, while only mild to moderate myelosuppression was noted. The vindesine and cisplatin regimen demonstrated significant activity against heavily pretreated small cell lung cancer, although chemotherapeutic response was poor in regions of prior irradiation.     

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.     

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.     

Treatment of non-small cell bronchogenic carcinoma with vinblastine and mitomycin: a Southwest Oncology Group Study

Forty-five patients with stage III M1 non-small cell bronchogenic carcinoma were treated with vinblastine (1 mg/m2 by iv bolus twice a day on 2 consecutive days) plus mitomycin (10 mg/m2 on Day 1). This treatment was repeated at 3-week intervals for three courses. Consolidation therapy with doxorubicin and cisplatin at doses of 50 mg/m2 each was administered to responders every 4 weeks for two courses, with subsequent vinblastine and mitomycin maintenance therapy every 6 weeks. Eleven partial remissions (24%) were achieved, with a median duration of remission of 16 weeks (range, 8-32) and a median survival of 19 weeks. No differences were seen in median duration of remission or survival by cell type or performance status.     

Extensive non-small cell lung cancer treated with mitomycin, cisplatin, and vindesine (MiPE): a Southwest Oncology Group Study

Ninety-seven previously untreated patients with metastatic non-small cell lung cancer were treated with combination chemotherapy consisting of mitomycin (10 mg/m2) on Day 1, cisplatin (50 mg/m2) on Days 1 and 22, and vindesine (3 mg/m2) on Days 1 and 22 (MiPE). MiPE was repeated at 6-week intervals until disease progression or unacceptable toxicity. The overall response rate was 33%. There were seven complete responses (7%) and 25 partial responses (26%). The median progression-free interval for responding patients was 7 months. Median survival for all patients was 5 months, with 16% surviving 1 year. One patient died from sepsis while neutropenic. The results with MiPE treatment for patients with non-small cell lung cancer compare favorably to other mitomycin-vinca combinations previously tested in the Southwest Oncology Group.     

Combination chemotherapy with vindesine, etoposide, and cisplatin in non-small cell lung cancer: a pilot study of the Southeastern Cancer Study Group

Ninety-two patients with advanced non-small cell lung cancer were treated with a combination chemotherapy regimen containing cisplatin, vindesine, and etoposide. Eighteen patients (20%) achieved major responses to therapy (three complete responders and 15 partial responders). Response rates were similar in each histologic subtype. Initial performance status was an important determinant of response; 42% of the patients with a Karnofsky performance status greater than or equal to 70% responded versus 5% of those with a performance status less than 50%. The median duration of partial response was 21 weeks; complete responders had a median response duration of 50 weeks. The median survival for the entire group was 23.5 weeks. Toxicity with this regimen was acceptable; myelosuppression was the major toxic effect and was severe in only 10% of the patients. This regimen produced response rates comparable to those reported with other combinations containing cisplatin. Survival advantage in patients receiving this treatment is not established.     

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.     

Trial of vindesine plus mitomycin in stage-3 non-small cell lung cancer. An active regimen for outpatient treatment

Ninety patients with stage-3 non-small cell lung cancer were given vindesine (3 mg/sq m) plus mitomycin (10 mg/sq m). Data on response are available for 84 adequately treated individuals (93 percent). For patients who had received no prior chemotherapy, the rate of major objective response was 36 percent (20/55). For previously treated patients the rate of major response was 17 percent (5/29). The drugs were routinely administered in the outpatient department without difficulty. Moderate or severe myelosuppression, neurotoxic, nephrotoxic, or pulmonary toxic effects, nausea, and vomiting occurred in less than 15 percent of all studied patients. Three-drug extravasation ulcerations occurred in 1,129 administrations of chemotherapy (0.3 percent). There were two treatment-related deaths, one from sepsis and one from the combination of mitomycin-induced pulmonary and renal toxic effects. The combination of vindesine plus mitomycin is an active, well-tolerated outpatient regimen for patients with non-small cell lung cancer who have not previously received chemotherapy. Further trials are warranted to compare this regimen to other active combinations and to use it as a component of a program of treatment using alternating regimens of chemotherapy.     

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.     

Combination chemotherapy for non-small cell lung cancer with doxorubicin and mitomycin or cisplatin and etoposide

The combinations of doxorubicin (40 mg/m2 iv every 3 weeks) and mitomycin (12 mg/m2 iv every 6 weeks) or cisplatin (80 mg/m2 iv every 3 weeks X 3, then every 6 weeks) and etoposide (80 mg/m2 iv on Days 1-3 every 3 weeks X 3, then every 6 weeks) were evaluated in a randomized phase II trial in 77 patients with measurable or evaluable non-small cell lung cancer. No patient had been pretreated with prior chemotherapy. The overall response rate for the doxorubicin and mitomycin regimen was 11% and for the cisplatin and etoposide regimen was 23%. Responses lasted a median of 5.5 months. Median survival was 7.0 months for the doxorubicin and mitomycin regimen and 8.0 months for the cisplatin and etoposide regimen. One treatment-related death was observed after doxorubicin and mitomycin in a patient who had received radiation therapy immediately prior to study entry. Otherwise, the hematologic toxicity of both chemotherapy regimens was moderate, with only six patients (10%) having World Health Organization grade 3 toxicity and no patients having World Health Organization grade 4 toxicity. However, subjective tolerance gastrointestinal upset) of the cisplatin and etoposide combination was poor.     

A prospective, multicentre clinical trial comparing cisplatin plus gemcitabine with cisplatin plus etoposide in patients with locally advanced and metastatic non-small cell lung cancer

OBJECTIVE: Cisplatin-gemcitabine (PG) and cisplatin-etoposide (PE) combinations are active regimens for non-small cell lung cancer (NSCLC). The present study aimed to compare PG with PE in the treatment of patients with stage IIIB and IV NSCLC. METHODOLOGY: We conducted a prospective, multicentre trial. A total of 166 patients were enrolled into the study and received either gemcitabine (1,000 mg/m(2)) on days 1, 8 and 15 plus cisplatin (80 mg/m(2)) on day 2 every 4 weeks, or etoposide (100 mg/m(2)) on days 1, 2 and 3 plus cisplatin (80 mg/m(2)) on day 1 every 3 weeks. RESULTS: The overall response rate was superior in the PG group (54.8%vs 39.0%, P=0.045). There was no significant difference in survival between the two groups, with respective median and 1-year survival of 38 weeks and 33.3% for the PG group, and 34 weeks and 23.2% for the PE group. There was also no statistical difference for time to progression between the two groups. Neutropenia and thrombocytopenia were seen more frequently in the PG group (grade 3 neutropenia, 33.3%vs 15.9%, P=0.012; grade 3 thrombocytopenia, 27.4%vs 3.7%, P<0.001 and grade 4 thrombocytopenia, 10.7%vs 1.2%, P=0.018). CONCLUSION: PG is an active chemotherapy regimen and has a better response rate than PE in advanced NSCLC, although there was no difference in time to progression and overall survival. A higher incidence of haematological toxicity was seen with PG than with PE.     

Comparing cisplatin plus etoposide with combination of mitomycin, ifosfamide and cisplatin in advanced non-small cell lung cancer patients

Cisplatin-etoposide (CE) and mitomycin, ifosfamide and cisplatin (MIC) combinations are active conventional regimens in non-small cell lung cancer (NSCLC). In this retrospective study, we compared response rates, survival, duration of response, time-to-progression and toxicity of CE with MIC regimens in treatment of previously untreated patients with stage IIIB and IV NSCLC. We first determined the patients with NSCLC who had stage IIIB or IV and received CE or MIC between January 1997 and December 2002 in our clinic. Out of the eligible patients, 45 received MIC, 167 received CE. In addition 45 MIC patients, we included 46 of the 167 CE patients in the study by selecting one patient of every three patient randomly. In CE protocol, cisplatin 80 mg/m(2) on day 1 and etoposide 100 mg/m(2) on days 1, 2, 3 (every three weeks); in MIC protocol, mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), cisplatin 50 mg/m(2) on day 1 (every three weeks) were performed. For statistical analysis, chi-square, t-test, Kaplan-Meier survival analysis, Cox regression analysis and logistic regression analysis were used by SPSS 11.5 computer program. The overall response rate was 33.3% in the MIC arm and 34.8% in the CE arm. A respective median survival was 28 weeks for the MIC arm and 35 weeks for the CE arm. Median duration of response and time to progression in each groups were 23 and 14 weeks in MIC arm and 32 and 22 weeks respectively. There was no statistical difference for response rates, duration of survival and response, time top progression and toxicity between the two arms. We consider that the combinations of MIC and CE have similar activity and they can be used confidently in advanced NSCLC.     

Comparison of vincristine and vindesine in the treatment of inoperable non-small cell bronchial carcinoma

Sixty-three patients with inoperable symptomatic non-small cell carcinoma of the bronchus were randomly allocated to receive either vincristine (1.4 mg/m2) or vindesine (3 mg/m2). These drugs were given weekly for four doses, then every 2 weeks for two further doses, and then continued monthly if there had been a response. Only five partial responses (greater than 50% reduction) were obtained with vindesine and none with vincristine. Disabling toxic effects occurred in 13 patients. This was more common with vindesine, but this group also received more prolonged therapy. Vindesine has modest activity against non-small cell carcinoma of the bronchus and may be more effective than vincristine, with similar toxicity.     

High-dose cisplatin with fluid and mannitol-induced diuresis in advanced lung cancer: a phase II clinical trial of the EORTC Lung Cancer Working Party (Belgium)

A phase II clinical trial of high-dose cisplatin (120 mg/m2 iv every 3 weeks), with fluid and mannitol-induced diuresis, was conducted in 81 patients with advanced lung cancer. Partial remissions were documented in 26% of 75 evaluable cases for a median duration of 3.5 months. Adenocarcinoma and small cell anaplastic carcinoma were more responsive than epidermoid carcinoma, with partial response rates of 35%, 30%, and 18%, respectively. The median survival of responders (8.5 months) was significantly longer than the survival of nonresponders (4 months) (P less than 0.02). Myelosuppression was mild. Renal toxicity with peak serum creatinine greater than 2.5 mg/100 ml occurred in eight patients, with one death occurring due to toxicity. Cisplatin is an active drug in advanced lung cancer.     

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.     

Combination chemotherapy with mitomycin and vindesine in advanced non-small cell lung cancer: a pilot study by the Lung Cancer Working Party (Belgium)

The combination of mitomycin plus vindesine in advanced non-small cell lung cancer induced an objective response rate of 23% in 43 evaluable patients: 33% in nonpretreated patients (nine responses among 27 patients) and 6% in pretreated patients (one response among 16 patients). Toxicity was tolerable. We conclude that the regimen was a moderately active and easy to administer treatment for advanced non-small cell lung cancer.     

Phase II trial of mitomycin, vindesine, and hexamethylmelamine in metastatic non-small cell bronchogenic carcinoma

Mitomycin (10 mg/m2 iv on Day 1), vindesine (3 mg/m2 iv on Days 1 and 8), and hexamethylmelamine (100 mg/m2/day orally on Days 1-14) was administered to 32 patients with metastatic non-small cell bronchogenic carcinoma. No patient had been previously treated with chemotherapy and Eastern Cooperative Oncology Group (ECOG) performance status was 0-1 in 21 of 32 patients. Eleven partial responses (34%) were observed, with a median duration of 9 weeks. No complete responses were observed in this group of patients, whose median survival duration was 22 weeks. Moderate leukopenia (median leukocyte count nadir, 2500/mm3) was the major toxic effect. Although this regimen is active and relatively nontoxic, it will not be utilized in future ECOG trials because it has not produced an apparent improvement in survival duration.     

紫杉醇联合顺铂治疗晚期非小细胞肺癌的临床观察

目的观察紫杉醇(PTX)加顺铂(CDDP)联合化疗治疗晚期非小细胞肺癌的近期疗效及毒副反应。方法PTX135~175mg/m2静脉滴注,第1天;CDDP75mg/m2,分三次用完。每21天为1个周期,连用2或3周期。结果可评价疗效者37例,其中PR16例,总有效率为43.2%。毒副反应主要是骨髓抑制和恶心呕吐。结论PTX DDP治疗晚期非小细胞肺癌可获得较高疗效,毒副反应轻,是一个较好的联合化疗方案。     

Cisplatin and vinblastine chemotherapy for metastatic non-small cell carcinoma followed by irradiation in patients with regional disease

Forty-four patients with non-small cell carcinoma of the lung were treated every 3 weeks with vinblastine (4 mg/m2/day iv X 2) and cisplatin (20 mg/m2/day iv X 3). Of the 28 patients with metastatic disease, eight (29%; 90% confidence interval of true response, 17%-47%) achieved objective response, for a median duration of 27 weeks. Median survival in this group was 47 and 28 weeks for responders and nonresponders, respectively. Of the 16 patients with advanced regional disease, 11 (69%; 90% confidence interval of true response, 49%-86%) achieved objective response. Thirteen of these patients received consolidation radiotherapy (4500 cGy/25 fractions/5 weeks), with a boost of 1000 cGy/5 fractions/1 week in those patients who achieved response. In the three patients who did not receive radiotherapy, two died during the induction phase, one from grade 4 leukopenia and sepsis and the second from unrelated factors. The third patient had systemic progression of disease during induction chemotherapy. Six patients experienced overall improvement in their chemotherapy response from the radiotherapy. Two patients who did not respond to the chemotherapy achieved partial response with irradiation. Four patients who had partial response to the chemotherapy achieved complete response with irradiation, and seven patients had no further change in their degree of response to irradiation. The overall median survival of this group was 81 weeks. Maintenance chemotherapy was not given. After radiotherapy, the site of first failure was outside the radiation field in nine of 13 patients (69%). Hematologic toxicity was dose-limiting. Other toxic effects that were not dose-limiting included nephrotoxicity, neurotoxicity, and acute nausea and vomiting. In the patients with advanced regional disease, there was no increase in the radiation toxicity attributable to the chemotherapy. We conclude that: (a) this dose schedule of vinblastine and cisplatin has reproducible activity in non-small cell carcinoma of the lung; (b) the response and median survival of patients with advanced regional disease are superior to those of patients with metastatic disease; and (c) in patients with advanced regional disease, treatment with chemotherapy followed by radiotherapy yielded an overall response rate of 81% (90% confidence interval of true response, 60%-93%) and improved survival compared to a similar group of patients studied by others receiving radiotherapy alone. We recommend further testing of this concept.     

培美曲塞治疗晚期非小细胞肺癌近期疗效及毒性反应研究

目的研究多靶点叶酸拮抗剂培美曲塞治疗晚期非小细胞肺癌(NSCLC)的近期疗效和毒性反应。方法收集我院2008年1月至2010年1月资料完整的晚期非小细胞肺癌患者共18例,男10例,女8例,中位年龄51岁(范围32～68岁),均经组织学和/或细胞学证实,因化疗后出现复发或进展而采用培美曲塞化疗。化疗方案为培美曲塞500mg/m2单药或联合顺铂75mg/m2,每3周重复;对接受两个或两个以上化疗周期的患者进行化疗效果及副反应评价。结果 18例可评价疗效,无完全缓解(CR)病例,部分缓解(PR)仅2例,稳定者(SD)共12例,4例疾病进展(PD)。全组有效率(CR+PR)为11.1%(2/18),疾病控制率(DCR)为77.8%(14/18)。中位生存时间9.2个月,中位疾病进展时间2.8个月,1年生存率为31.2%。未出现化疗相关死亡,毒副反应主要为I～Ⅲ度胃肠道反应和骨髓抑制。结论培美曲塞治疗复治晚期NSCLC安全有效,耐受性良好。