多西紫杉醇联合长春瑞滨二线治疗晚期非小细胞肺癌的临床研究

Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.     

A phase II study of docetaxel and vinorelbine combination chemotherapy in patients with advanced non-small cell lung cancer

A phase II study was conducted to determine the efficacy and the safety of docetaxel combined with vinorelbine as first-line chemotherapy in patients with metastatic or unresectable non-small cell lung cancer (NSCLC). 39 patients, median age 54 years (range: 35-69), with stage IIIB (5 patients; 13%) or IV (34 patients; 87%) NSCLC were treated with 75 mg/m(2) docetaxel given intravenously (i. v.) over 1 h on day 1 and with 20 mg/m(2) vinorelbine given i.v. over 15 to 30 min on days 1 and 5. Cycles were repeated every 3 weeks. 9 of the 39 patients had a partial response (overall response rate 23.1%, 95% confidence interval (CI): 11.1-39.3%) with a median duration of response of 20 weeks (95% CI; 17-30). The median survival was 40 weeks (95% CI: 21-49 weeks) with a 1-year survival rate of 31% in the intent-to-treat population. Neutropenia grade IV occurred in 33 patients (92%). 16 patients (41%) experienced febrile neutropenia with a concomitant stomatitis in 9 patients (23%). One patient died due to febrile neutropenia associated with a grade 4 stomatitis and 1 patient due to a septicaemia concomitant with a grade 4 neutropenia. Although the combination of docetaxel and vinorelbine is feasible, the efficacy does not seem to be improved compared with single-agent docetaxel or vinorelbine and the rate of febrile neutropenia is unacceptable in this population with incurable disease. Therefore, different doses and/or schedules are to be explored.     

Phase I study of paclitaxel (Taxol) plus vinorelbine (Navelbine) in patients with untreated stage IIIb and IV non-small cell lung cancer

A dose escalation study of paclitaxel in combination with vinorelbine was conducted in 21 patients with previously untreated stage IIIb or IV non-small cell lung cancer (NSCLC). All three patients treated with the initial dose of paclitaxel 135 mg/m(2) administered as a 1-h intravenous infusion and vinorelbine 25 mg/m(2) experienced dose-limiting toxicity (febrile neutropenia). After modification of the dosing schedule, the MTD of paclitaxel was found to be 115 mg/m(2) when combined with vinorelbine 20 mg/m(2) on day 1, followed by vinorelbine 20 mg/m(2) on day 5. Partial responses were achieved in 24% of patients, with a median duration of response of 126 days (range from 84 to 484 days) and a 1-year survival rate of 42%. In conclusion, haematologic toxicity (febrile neutropenia/neutropenia) severely restricts the dosing schedule of combined paclitaxel and vinorelbine, and possibly limits anti-tumour efficacy.     

Challenging the platinum combinations in the chemotherapy of NSCLC

In previously untreated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) the combination of docetaxel and gemcitabine is active and well tolerated. In the phase II setting using a 3-week schedule, response rates (RR) ranged from 25 to 50%, and median survival from 11 to 13 months. Preliminary data with weekly and bi-weekly schedules indicate maintained efficacy while reducing the risk of neutropenia. A randomized phase III trial has shown that the combination of docetaxel and gemcitabine is as active as docetaxel plus cisplatin, achieving a 1-year survival rate of 39%, with significantly less neutropenia and gastro-intestinal toxicity. The combination of docetaxel with vinorelbine is equally active and the associated toxicities are manageable. In phase II studies the average response rate is 40%, and in one study using a 2-week schedule the 1-year survival rate was 60%. With this combination neutropenia is the commonest adverse event while clinically significant neuropathy is infrequent. In a randomized phase II trial, docetaxel plus cisplatin was compared to docetaxel plus irinotecan. The non-platinum doublet achieved comparable levels of activity, though with a different toxicity profile (more diarrhea but less nausea and vomiting). The combination of docetaxel with irinotecan and carboplatin has achieved 1-year survival of 55%. All three docetaxel combinations (gemcitabine, vinorelbine, and irinotecan) could provide a valuable alternative to platinum-based chemotherapy and should be further evaluated in phase III setting.     

Weekly vinorelbine and docetaxel as second-line chemotherapy for pretreated non-small cell lung cancer patients: a phase I-II trial

Docetaxel was proven to be effective as second-line therapy for patients with advanced NSCLC after failure of platinum-based front-line chemotherapy. We designed this phase I/II study to define the Maximum Tolerated Dose of weekly docetaxel combined with weekly vinorelbine, and subsequently evaluate tolerability and activity of this schedule in NSCLC patients who were progressive after treatment with either cisplatin and gemcitabine or carboplatin and paclitaxel regimens. To be eligible for the study, patients were required to have a WHO performance status < or =2, failure after at least two cycles of first platinum-based chemotherapy, and no prior treatment with docetaxel and vinorelbine. A total of 27 patients were enrolled in this phase I/II study. A weekly docetaxel dose of 25 mg/m2 was recommended in combination with fixed vinorelbine dose of 20 mg/m2, and 24 patients were treated at this dose level. Severe neutropenia (62%) and febrile neutropenia (29%) were the most frequent toxicities, with 83% of patients requiring dose modification or delay. In the phase II study, 5 (21%) patients obtained a partial response, 8 (33%) patients had stable disease, whereas 10 (42%) patients progressed. After a median follow-up of 18.7 months, median survival was 8 months, with 30% surviving at 1 year. Regardless of the use of weekly docetaxel schedule, this regimen was highly myelosuppressive, and did not seem to improve response rate and survival compared to single-agent docetaxel. No further developments of this schedule are warranted.     

Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel-cisplatin versus vinorelbine-cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study.

BACKGROUND: This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC). METHODS: Overall, 115 patients received DC (docetaxel 75 mg/m(2) and cisplatin 100 mg/m(2) both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m(2)/week on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m(2) days 1 and 8 (A2), or docetaxel 100 mg/m(2), day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR). RESULTS: Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms A1 and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC. CONCLUSIONS: The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of long-term survivors, despite the absence of efficacy of the second-line in our study.     

Alternating doublets: establishing the optimal multifractionated dosing schedule to administer docetaxel, cisplatin, gemcitabine, and vinorelbine in combination

The purpose was to determine the optimal multifractionated (MF) dosing schedule to permit the delivery of four active agents in nonsmall cell lung cancer simultaneously in alternating doublets (docetaxel-cisplatin alternating with gemcitabine-vinorelbine). Three MF schedules were used: schedule A weekly; schedule B twice weekly for 2 weeks repeated every 21 days; and schedule C twice weekly every other week. Dose fractions were fixed for each component drug: docetaxel 50 mg/m² plus cisplatin 20 mg/m² and gemcitabine 500 mg/m² plus vinorelbine 25 mg/m². GCSF 480 µg was administered as a single dose concomitant with chemotheray if the WBC was between 1500 and 3500 cells/mm³. Hematological toxicity, particularly leukopenia and anemia, was the predominant adverse effect observed and was demonstrated on all three schedules. Schedule B was not feasible in that none of the seven cycles were completed and six of seven required hospitalization for febrile neutropenia. The delivery of a four-drug combination chemotherapy regimen consisting of docetaxel, cisplatin, gemcitabine, and vinorelbine is feasible with an alternating doublet multifractionated dosing scheme with either a weekly or twice weekly every other week schedule.     

Weekly Vinorelbine and Docetaxel as Second-Line Chemotherapy for Pretreated Non-Small Cell Lung Cancer Patients: a Phase I-II Trial

Abstract

Docetaxel was proven to be effective as second-line therapy for patients with advanced NSCLC after failure of platinum-based front-line chemotherapy. We designed this phase I/II study to define the Maximum Tolerated Dose of weekly docetaxel combined with weekly vinorelbine, and subsequently evaluate tolerability and activity of this schedule in NSCLC patients who were progressive after treatment with either cisplatin and gemcitabine or carboplatin and paclitaxel regimens. To be eligible for the study, patients were required to have a WHO performance status ≤2, failure after at least two cycles of first platinum-based chemotherapy, and no prior treatment with docetaxel and vinorelbine. A total of 27 patients were enrolled in this phase I/II study. A weekly docetaxel dose of 25 mg/m² was recommended in combination with fixed vinorelbine dose of 20 mg/m², and 24 patients were treated at this dose level. Severe neutropenia (62%) and febrile neutropenia (29%) were the most frequent toxicities, with 83% of patients requiring dose modification or delay. In the phase II study, 5 (21%) patients obtained a partial response, 8 (33%) patients had stable disease, whereas 10 (42%) patients progressed. After a median follow-up of 18.7 months, median survival was 8 months, with 30% surviving at 1 year. Regardless of the use of weekly docetaxel schedule, this regimen was highly myelosuppressive, and did not seem to improve response rate and survival compared to single-agent docetaxel. No further developments of this schedule are warranted.     

Phase II study of docetaxel/vinorelbine in patients with non-small-cell-lung cancer previously treated with platinum-based chemotherapy

The aim of this phase II trial was to assess the efficacy and tolerability of docetaxel/vinorelbine as second-line therapy. Thirty-two patients with a performance status (PS) of 相似文献   

Phase II study of vinorelbine/ifosfamide/cisplatin for the treatment of advanced non-small-cell lung cancer

PURPOSE:: to evaluate the combination of vinorelbine, ifosfamide and cisplatin(VIP) in patients with advanced nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS:: Seventy-six untreated patients with stages IIIB-IV NSCLC; thechemotherapy regimen consisted of vinorelbine (25 mg/sqm ondays 1 and 8), ifosfamide (3 g/sqm on day 1 with uroprotectivemesna), and cisplatin (80 mg/sqm on day 1). The cycles wereadministered on an out patient basis every 3 weeks. RESULTS:: Leukopenia was the most frequent toxicity: grades 3–4neutropenia was observed in 26% of the cycles and 19 episodesof febrile neutropenia were reported in 289 evaluable courses.Filgrastim 5 µg/kg was administered in 27% of the courses.Sixty-seven of 76 patients were evaluable for response: theoverall response rate was 51% (95% confidence interval 35%–%)with 2 complete responses (3%) and 32 (48%) partial responses.No significant differences in response rate were observed accordingto histology or stage of disease. The median time to progressionwas 6 months (range 1 to 29+) and the median overall survival10 months (range 1–33+). CONCLUSION:: The combination of vinorelbine, ifosfamide and cisplatin inthe dose and schedule employed in this trial shows an interestingresponse rate with acceptable toxicities. This regimen shouldbe tested in the multimodality therapy of stage IIIA/B NSCLC. vinorelbine, ifosfamide, cisplatin, non-small-cell, lung cancer     

Randomized phase II trial of gemcitabine plus weekly versus three-weekly paclitaxel in previously untreated advanced non-small-cell lung cancer.

INTRODUCTION: Gemcitabine and paclitaxel (Taxol) each provides an efficacious non-platinum option for the treatment of advanced non-small-cell lung cancer (NSCLC), but the optimal dosage and schedule of the two agents used in combination are not well defined. METHODS: Previously untreated patients with advanced NSCLC were randomized to receive gemcitabine-paclitaxel on a traditional three-weekly schedule (Arm A) or a novel weekly schedule (Arm B) as follows-Arm A (three-weekly): gemcitabine 1000 mg/m2 infused>30 min on days 1 and 8 and paclitaxel 200 mg/m2 infused>3 h on day 1 of a 21-day cycle or Arm B (weekly): gemcitabine 1000 mg/m2 infused>30 min and paclitaxel 100 mg/m2 infused>1 h, both administered on days 1 and 8 of a 21-day cycle. RESULTS: One hundred patients received at least one dose of treatment. The weekly schedule, Arm B, was more efficacious and less hematologically toxic than Arm A. Confirmed complete and partial response rates were 28.2% and 26.8%, respectively. Median survival was 10.3 months on Arm B and 7.9 months on Arm A (log-rank P=0.10); 1- and 2-year survival rates also favor Arm B: 42.0% versus 34.0% and 18.0% versus 6.0%. Progression-free survival was 5.8 versus 4.8 months, again favoring Arm B (log-rank P=0.06). There was a two-fold lower frequency of grade 3/4 hematologic events with Arm B as follows: neutropenia (16% versus 30%), thrombocytopenia (4% versus 8%), and anemia (2% versus 6%). One patient (2%) in each treatment group developed febrile neutropenia. CONCLUSION: In this trial, both schedules were efficacious and tolerable, although the weekly schedule resulted in improved survival and lower hematologic toxicity compared with a three-weekly schedule. The weekly schedule of gemcitabine-paclitaxel indicates an improved therapeutic index.     

Weekly combination of docetaxel and vinorelbine in metastatic breast cancer: a phase I/II study

OBJECTIVE: A phase I/II study was carried out to determine the recommended dose (RD) and to assess the efficacy and safety of a weekly docetaxel-vinorelbine combination in advanced breast cancer (ABC) patients. METHODS: Twenty-four female patients with histologically proven ABC received intravenous vinorelbine (20 min) followed by intravenous docetaxel (1 h) on days 1, 8 and 15 of a 4-week cycle. Starting doses were 20 mg/m2 docetaxel and 15 mg/m2 vinorelbine. RESULTS: Patients had a median age of 62 years (range 38-74 years), and 92% had performance status 0-1. The most common sites of metastases were the lungs (32%), liver (29%) and bone (14%). Seventy-one percent of patients had received prior chemotherapy. The RDs of docetaxel and vinorelbine were 20 and 15 mg/m2, respectively. Dose-limiting toxicities were neutropenia-induced dose delay and febrile neutropenia. The response rate at the RD was 43%. All responses were seen in non-pretreated patients. Grade 3-4 neutropenia occurred in 80% of patients, 3 of whom experienced febrile neutropenia and died as a possible consequence of neutropenia. CONCLUSION: This docetaxel-vinorelbine combination as first-line therapy yields a response rate similar to that of single-agent docetaxel as second-line therapy. However, given the high rate of myelotoxicity, higher doses are not feasible.     

Phase I and II trials of vinorelbine with carboplatin for patients 75 years of age or older with previously untreated non-small-cell lung cancer

BackgroundThe safety and efficacy of platinum-based combination chemotherapy for elderly patients with advanced non–small-cell lung cancer (NSCLC) remains unclear. We conducted phase I and phase II trials of a combination of vinorelbine and carboplatin for patients ≥75 years of age and with advanced NSCLC.Patients and MethodsPreviously untreated patients (≥75 years of age) with stage IIIB or IV NSCLC were enrolled. Based on a 4-week cycle, vinorelbine was given on days 1 and 8, and carboplatin was given on day 1. Dose-limiting toxicity was defined as grade 4 hematologic toxicity that lasted 4 days or more, febrile neutropenia; grade 3 or worse nonhematologic toxicities; or the omission of vinorelbine administration on day 8 in the first cycle.ResultsThirteen patients were enrolled in phase I. dose-limiting toxicity was grade 4 neutropenia that lasted 4 days or more, observed in 2 of 4 patients at level 4. Phase II study used the dose of level 3 (20 mg/m² vinorelbine, area under the curve of 4 mg/mL/min carboplatin). Forty-two patients were enrolled. The response rate was 14.6% of 41 assessable patients (95% CI, 3.8-25.4). The median time to progression was 98 days (95% CI, 61-135 days), and the median survival time was 366 days (95% CI, 321-411 days). All toxicities were mild and manageable.ConclusionUse of 20 mg/m² vinorelbine on days 1 and 8, followed by carboplatin area under the curve of 4 mg/mL/min on day 1 every 4 weeks warrants a phase III study for elderly patients with advanced NSCLC.     

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study

Background Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. Methods This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m² (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m² (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. Results Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1–6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29–59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3–4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3–4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). Conclusion Gemcitabine 1,000 mg/m² on days 1 and 8 in combination with docetaxel 85 mg/m² on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.     

Continuous-infusion vinorelbine for the treatment of advanced non-small-cell lung cancer: a phase I/II study

BACKGROUND: In this phase I/II trial, the maximum tolerated dose (MTD) and activity of vinorelbine administered in continuous infusion as first-line treatment for advanced non-small-cell lung cancer (NSCLC) was determined in 25 consecutive chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Vinorelbine was administered as an initial intravenous (I.V.) bolus of 8 mg/m(2) on day 1 followed by a 4-day continuous I.V. infusion at 5 different 24-hour dose levels to be repeated every 21 days. All 25 patients (159 cycles) were evaluable for response. The MTD was 8 mg/m(2) bolus followed by a continuous I.V. infusion of 11 mg/m(2) per day over 4 days. RESULTS: The dose-limiting toxicities were febrile neutropenia in 6 patients and grade 3 mucositis in 2 patients. There was less neurotoxicity and constipation and more mucositis compared with the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Treatment responses were observed in 6 patients: 1 complete response and 5 partial responses. The overall response rate was 24% (95% confidence interval [CI], 8%-40%). Median time to progression was 4 months (95% CI, 2-11 months), and median survival was 6 months (95% CI, 2-18 months). CONCLUSION: The results demonstrate that, in this setting of first-line treatment of NSCLC, vinorelbine administered as an 8 mg/m(2) bolus followed by a continuous infusion of 11 mg/m(2) per day over 4 days is the recommended schedule. Further trials are necessary to establish activity and possible benefits of combination with other agents.     

Trials of vinorelbine and docetaxel in the treatment of advanced non small-cell lung cancer

Docetaxel was chosen for study in the combination chemotherapy of advanced non small-cell lung cancer on the basis of its reproducible high single-agent activity, novel mechanism of action, and relative lack of neurotoxicity. Preclinical and clinical data suggested schedule-dependent synergism with vinorelbine. Trials of docetaxel and vinorelbine have explored a variety of schedules. One approach has been to give docetaxel on day 1 of a 3-week cycle with vinorelbine on day 0 or days 1 and 5. Febrile neutropenia and non-neutropenic infections have been dose limiting, and low-dose intensity (8-13 mg/m2/week) of vinorelbine has been achieved. Our phase I study showed that docetaxel 60 mg/m2 and vinorelbine 45 mg/m2 every 2 weeks could be safely given with prophylactic filgrastim. In the ensuing phase II trial, we observed a 51% confirmed response rate in 35 patients (95% confidence interval [CI]: 34-68). With a median follow-up of 12 months, the predicted median and 1-year survivals are 14 months and 60%, respectively. Use of prophylactic filgrastim and the every-2-week schedule of administration allowed for single-agent dose intensity of both drugs to be given. Febrile neutropenia occurred in five patients and 5/384 cycles. Cumulative toxicities of excessive lacrimation, fatigue, and onycholysis were observed. More recently, a weekly schedule of administration for both drugs has been studied. Docetaxel and vinorelbine appear highly active together when given on an every-2-week schedule with prophylactic filgrastim, and the combination may offer one alter-native to cisplatin-based therapy. However, confirmatory phase II and III studies are needed. Certain cumulative toxicities (onycholysis, lacrimation) may limit the duration of therapy. Application of this regimen for a shorter period, such as in induction or postoperative settings, may provide optimal benefit while minimizing toxicity.     

Biweekly gemcitabine plus vinorelbine in first-line metastatic breast cancer: efficacy and correlation with HER2 extracellular domain

Purpose To assess the toxicity and efficacy of biweekly gemcitabine plus vinorelbine in first-line advanced breast cancer, and to establish whether circulating HER2 ECD levels correlate with the efficacy of the combination. Patients and methods 52 patients were treated with gemcitabine 2500 mg/m² plus vinorelbine 30 mg/m², both on day 1 of 14-day cycles, for a maximum of 10 cycles. Baseline serum levels of HER2 ECD were assessed with an ELISA. Results All patients were evaluable for toxicity, and 50 for efficacy. Overall toxicity was moderate. Grade 3 neutropenia occurred in 35% of patients and grade 4 in 19%. Other grade 3 toxicities were observed in less than 6%. There was one episode of febrile neutropenia, and one death after cycle three. Overall response rate was 52% (95% CI: 38% to 66%), with 2 patients achieving a CR (4%). Response rate did not correlate with HER2 ECD, with 50% of HER2 ECD positive patients responding, vs 48.5% of the HER2 ECD negative. Median overall survival was 24.6 months. Conclusion Gemcitabine plus vinorelbine, given as an every-two-week schedule, is an active regimen in advanced breast carcinoma. This combination can be an option when anthracyclines and taxanes are not preferred. HER2 ECD has no predictive value in this non-taxane combination.     

国产多西他赛治疗乳腺癌和非小细胞肺癌的临床观察

目的:评价国产多西他赛(深圳万乐医药公司产品)单药以及多西他赛 顺铂联合化疗方案对乳腺癌和非小细胞肺癌的临床疗效和安全性,并以进口多西他赛(安万特公司) 顺铂联合化疗方案作对照.方法:1)单药治疗分为2组:多西他赛(万乐)75mg/m2第1天静脉滴注,21天为一周期,治疗乳腺癌(A组)和非小细胞肺癌(B组);2)联合治疗分为4组:乳腺癌患者随机分为多西他赛(万乐)70mg/m2 顺铂80mg/m2(C组),或泰索帝(进口)70mg/m2 顺铂80mg/m2(D组),21天为一周期;肺癌患者随机分为多西他赛(万乐) 顺铂(E组)或泰索帝(进口) 顺铂(F组),方案与乳腺癌相同.结果:147例患者中138例可评价疗效,141例可评价不良反应,单药有效率乳腺癌(A组)21.7%,单药非小细胞肺癌(B组)6.1%,联合治疗组有效率C组60.0%,D组35.0%,E组23.8%,F组28.6%.不良反应主要为骨髓抑制、恶心呕吐、脱发.联合治疗方案多西他赛(万乐)组与泰索帝(安万特)组比较,疗效和不良反应相似.结论:多西他赛(万乐)单药及联合顺铂方案治疗乳腺癌和非小细胞肺癌安全有效,耐受性好,与进口泰索帝疗效和不良反应相似.     

Daily times four vinorelbine plus cisplatin in advanced non-small-cell lung cancer: A phase II trial of a novel schedule

Purpose: To evaluate the efficacy of a novel multiday schedule of vinorelbine and cisplatin in patients with advanced NSCLC.Patients and methods: Thirty patients were enrolled, including 27 patients with stage IV disease, and 11 patients with performance status of 2. They received a maximum of four chemotherapy cycles with cisplatin 20 mg/m²/day and vinorelbine 15 mg/m²/day intravenously (i.v.) for four consecutive days, every three weeks, with prophylactic filgrastim.Results: Sixteen patients responded (53%, 95% confidence interval (95% CI): 34%–72%), including two complete and fourteen partial confirmed responses. Median survival for all patients was 8.1 months, with actuarial one-year and two-year survival rates of 40% and 15%. Despite prophylactic filgrastim, the delivered vinorelbine dose intensity of 16.8 mg/m²/week caused febrile neutropenia in 48% of patients (16% of cycles), resulting in one treatment-related death. Common nonhematologic toxicities included delayed emesis, asthenia, and constipation.Conclusions: This multiday vinorelbine–cisplatin schedule is highly active against advanced NSCLC but results in frequent neutropenic complications. The myelotoxicity and antitumor efficacy of vinorelbine in NSCLC patients may be schedule-dependent.     

Clinical data and pharmacokinetics of a docetaxel-vinorelbine combination in anthracycline resistant/ relapsed metastatic breast cancer

The aim of this study was to evaluate the pharmacokinetic parameters, efficacy and toxicity of a docetaxel and vinorelbine combination in metastatic breast cancer patients previously treated with anthracycline. A population of 40 patients was analyzed; 30 patients (75%) had visceral metastases as the dominant site of disease, including 20 patients (50%) with liver metastases. Three or more organs were involved in 43% of patients. All patients had received prior anthracycline therapy. Five patients (12%) had primary resistant disease, 10 patients (25%) secondary resistant disease and 25 patients (63%) had progressive metastatic breast cancer after first-line chemotherapy. Docetaxel and vinorelbine were given at 80 mg/m2 and 20 mg/m2 i.v., respectively, on day 1 every 3 weeks. After a median of 5 cycles, it was found that 5 patients had a complete remission (13%), 19 a partial remission (48%), 9 had stable disease (22%) and 7 had progressive disease (17%). Response rates in patients with visceral and liver metastases were 57% and 50%, respectively. After a median follow-up of 24 months (13-36), median time to progression was 8.5 months and median overall survival 17 months. Grade 4 neutropenia was observed in 78% of courses (febrile neutropenia in 9%). Possible pharmacokinetic interactions were studied in 23 patients by administering docetaxel immediately followed by vinorelbine (protocol A) or vinorelbine followed by docetaxel (protocol B). Patients in protocol B had significantly higher vinorelbine plasma levels and more pronounced neutropenia. Docetaxel plus vinorelbine is an effective combination in anthracycline resistant/relapsed metastatic breast cancer. The administration sequence docetaxel --> vinorelbine is safer than the reverse order.