Gemcitabine and vinorelbine in advanced nonsmall cell lung carcinoma: a phase II study

BACKGROUND: The authors conducted a Phase II study to evaluate the activity of the combination of gemcitabine and vinorelbine in patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: Patients were eligible if they had Stage IIIB (malignant pleural effusion) or Stage IV NSCLC, no prior chemotherapy, and Cancer and Leukemia Group B performance status (PS) 0-2. Patients with brain metastases were eligible if they were neurologically stable after brain irradiation. Thirty-three patients from participating institutions were enrolled. One patient was ineligible due to untreated brain metastases. Patients were treated with gemcitabine 1250 mg/m(2) over 30 minutes (1000 mg/m(2) for the first 6 patients) and vinorelbine 25 mg/m(2) over 6 minutes, both administered intravenously on Days 1 and 8 every 21 days. Treatment was planned for a total of six cycles or more if the patient had persistent benefit. Growth factors were not allowed. RESULTS: Among all 32 eligible patients, there were 8 partial responses, for an overall response rate of 25% (95% confidence interval [CI], 11.5-43. 4%). The median survival time was 8.3 months and the 1-year survival rate was 38% (95% CI, 24-59%). Patients with PS 0-1 had a median survival of 11.7 months and a 1-year survival rate of 48%. Grade 3 and 4 neutropenia was observed in 13% and 25% of the 148 treatment cycles, respectively. One patient died of neutropenic sepsis. Only 2 episodes of Grade 3 and 4 thrombocytopenia were observed. Nonhematologic toxicity was minimal. CONCLUSIONS: Gemcitabine and vinorelbine is an active and well-tolerated regimen in patients with advanced NSCLC, with response and survival rates at least comparable to those achieved with standard platinum-based regimens. This combination may be particularly suitable for the elderly or for patients who cannot tolerate more toxic platinum-based regimens.     

Second-line treatment with gemcitabine and vinorelbine in non-small-cell lung cancer (NSCLC) cisplatin failures: a pilot study

PURPOSE: This pilot study was designed to evaluate the efficacy and toxicity of the gemcitabine/vinorelbine combination in non-small-cell lung cancer (NSCLC) patients who had failed cisplatin-based first-line chemotherapy. PATIENTS AND METHODS: Eligible patients had refractory or resistant NSCLC, WHO performance status 0-2, adequate hematologic parameters and normal hepatic, renal and cardiac function. Gemcitabine (1200 mg/m2) was administered on days 1, 8 and 15; vinorelbine (25 mg/m2) was administered on days 1 and 8, every 4 weeks until patients experienced disease progression. RESULTS: From September 1997 to March 1998, 16 patients were enrolled (six: stage IIIB: ten: stage IV). All 16 patients were assessable for toxicity and evaluated for response. One complete (6.25%) response and no partial responses were observed. Median survival was 25 weeks (95% CI 19-30). A median of 3.31 courses per patient was administered, and the median interval between courses was 28 days. The median delivered dose was 664.85 mg/m2 per week of gemcitabine and 10.71 mg/m2 per week of vinorelbine, corresponding to a relative dose intensity of 0.73 and 0.85, respectively. Grade 2/3 thrombocytopenia occurred in 13 (24.52%) of 53 courses administered. Neutropenia Grade 2/3 occurred in 14 courses (26.41%). There were seven (13.20%) episodes of fever related to the drug administration. Mild asthenia was observed in six (37.5%) patients. Other toxicities were mild to moderate. CONCLUSION: These results suggest that this gemcitabine/vinorelbine combination is not an active salvage regimen in patients with refractory NSCLC. The combination merits further evaluation with modified regimens.     

Ifosfamide, vinorelbine and gemcitabine in advanced non-small cell lung cancer. A phase I study

The objective of this phase I study was to identify the maximum tolerated dose (MTD) and toxicity of a three drug, platinum-free regimen, including gemcitabine, ifosfamide and vinorelbine, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). 33 chemotherapy-na?ve patients with histologically confirmed, unresectable NSCLC, received fixed doses of ifosfamide (1500 mg/m2 days 1-3 with mesna) and vinorelbine (25 mg/m2 days 3 and 8). The gemcitabine dose was escalated from 500 to 1200 mg/m2 on days 3 and 8 every third week. The escalation was stopped at dose level 4 (gemcitabine 1200 mg/m2) since all 3 patients of this cohort showed dose-limiting thrombocytopenia and/or neutropenia at treatment cycle 1. The dose recommended for phase II trials is: gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 given on days 3 and 8 plus ifosfamide 1500 mg/m2 on days 1-3. An encouraging response rate of 50% (95% confidence interval (CI): 32-68%) was observed in 32 patients evaluated. Our results show that ifosfamide, vinorelbine and gemcitabine can be safely administered as outpatient chemotherapy for NSCLC. Myelosuppression is the dose-limiting toxicity (DLT) of this regimen with no major subjective side-effects observed.     

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.     

A phase II trial of weekly paclitaxel and gemcitabine in non-small cell lung cancer patients previously treated with platinum and vinorelbine

This study evaluated the activity and toxicity of a weekly paclitaxel plus gemcitabine combination as second-line treatment in patients with advanced non-small cell lung cancer (NSCLC). Paclitaxel 80 mg/m2 on days 1, 8 and 15 and gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks were administered to 34 consecutive, advanced NSCLC patients uniformly pretreated with cisplatin or carboplatin and vinorelbine. The median time interval from first- to second-line treatment was 8 weeks (range 1-72). A total of 124 cycles with a median of 3 cycles per patient were administered (range 1-6). Four patients (12%) achieved a partial response (95% confidence interval: 1-23%), 17 had stable disease (50%) and 12 progressed (37%). Three responses were observed in 14 patients showing disease response or stabilization to previous platinum therapy. The median survival was 28 weeks (range 3-91), the median progression-free survival was 12 weeks (range 3-50) and the 1-year survival rate was 23%. The toxicity profile was favorable. In conclusion, a weekly schedule of paclitaxel plus gemcitabine as a second-line regimen has moderate activity and good tolerability in NSCLC patients not refractory to previous platinum-vinorelbine treatment.     

Sequential chemotherapy with paclitaxel plus cisplatin, followed by vinorelbine, followed by gemcitabine in advanced non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 001)

Aim of this study was to determine the activity and toxicity of a sequential chemotherapy regimen in advanced non-small cell lung cancer (NSCLC). Fifty-one previously untreated stage IIIB/IV NSCLC patients were enrolled to receive two cycles of cisplatin plus paclitaxel (80/175 mg/m(2) every 21 days), followed by two cycles of vinorelbine (30 mg/m(2) on days 1 and 8 every 21 days), followed by two cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days). Forty-one patients (82%) completed the planned six cycles. Grade 3-4 neutropenia was the major toxicity (41% of patients) and it was mainly associated with vinorelbine administration. Response rate after cisplatin plus paclitaxel was 18%; this percentage increased to 41% after vinorelbine, and it reached 43% upon completion of the entire six cycle treatment program. Median survival time was 14.4 months, 1-year survival rate was 53%, and 2-year survival rate was 18%. Median time to disease progression was 6.8 months. This sequential chemotherapy regimen is feasible and active in patients with advanced NSCLC. This pilot experience provides the basis for an ongoing randomized phase III trial comparing our sequential regimen versus cisplatin plus gemcitabine.     

Gemcitabine plus vinorelbine for the treatment of advanced non-small cell lung cancer

The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy regimen of weekly gemcitabine and vinorelbine in patients with advanced non-small cell lung cancer (NSCLC). 40 chemotherapy-naı̈ve patients with stage IIIB/IV NSCLC were included. The doses of gemcitabine and vinorelbine were 1000 and 25 mg/m², respectively, given on days 1, 8 and 15, every 28 days. 38 patients were evaluable for response. One patient achieved a complete response (CR) and 10 attained a partial response (PR), for an overall response rate (ORR) of 29% (95% confidence interval (CI): 15–43%). 47% of patients experienced a clinical benefit. The main toxicity consisted of grade 3 anaemia and neutropenia in 5% of patients. Non-haematological toxicity was minimal. The dose-intensities were 744 mg/m²/week for gemcitabine and 15 mg/m²/week for vinorelbine. 40% of the patients survived for longer than 1 year. The median time to progression was 4 months and the median survival 8.5 months (95% CI: 3.1–13.8 months). The weekly administration of gemcitabine and vinorelbine is very well tolerated and results in an acceptable response rate for the treatment of NSCLC.     

Gemcitabine and vinorelbine as second-line therapy for non-small cell lung cancer after treatment with paclitaxel plus platinum

OBJECTIVE: To investigate the activity and feasibility of combination therapy of gemcitabine and vinorelbine for patients with advanced NSCLC after the failure of initial treatment with paclitaxel plus platinum. METHODS: From March 2000 to August 2002, 38 evaluable patients (median age 55 years) with NSCLC, who had failed to recover after treatment with paclitaxel plus platinum, received vinorelbine (30 mg/m(2) i.v.) followed by gemcitabine (1000 mg/m(2) i.v.), both being administered on days 1 and 8 and recycled every 3 weeks. RESULTS: Objective responses were as follows: partial response, 8/38 [21%; 95% confidence interval (CI) 8-23%]; and stable disease, 21/38 (55%). Median time to progression was 3.9 months and the median overall survival was 8.1 months. Grades III and IV neutropenia were seen in 17 and 11% of patients, respectively. CONCLUSION: This combination chemotherapy with gemcitabine and vinorelbine is active and highly tolerable as a second-line therapy for NSCLC.     

Gemcitabine plus vinorelbine as first-line chemotherapy in advanced nonsmall cell lung carcinoma a phase II trial

BACKGROUND: Response and survival in patients with advanced or metastatic nonsmall cell lung carcinoma (NSCLC) remain poor. As single agents, the nucleoside analog gemcitabine, and the semisynthetic vinca alkaloid vinorelbine, have been shown to be effective in NSCLC and to have a low toxicity profile. METHODS: Fifty-four chemotherapy-naive patients with NSCLC Stage IIIB (any TN3M0 or T4 any NM0) or IV (any T any NM1) were enrolled in this single-institution Phase II study. Gemcitabine 1250 mg/m(2) and vinorelbine 25 mg/m(2) were both administered on Days 1 and 8 every 3 weeks for up to 9 courses unless disease progression or severe toxicity required their discontinuation. RESULTS: Partial tumor regression was observed in 16 patients, for an overall response rate of 30% (95% confidence interval, 18.4-46.7%) on an intent-to-treat basis. The median time to progression was 5 months (range, 3-20). The median survival was 12 months (range, 5-42+); 1-year and 2-year survival rates were 49.1% and 17%, respectively. Hematologic toxicity was mild with only 11% of the patients developing Grade 3 neutropenia. None of the patients developed any Grade 4 toxicity. CONCLUSIONS: The combination of gemcitabine plus vinorelbine is feasible on an outpatient basis. The good activity and tolerability of the regimen make it a suitable candidate for further trials, using platinum-based regimens as comparators and possibly selecting elderly and less fit patients.     

Long-duration, weekly treatment with gemcitabine plus vinorelbine for non-small cell lung cancer: a multicenter phase II study

In this phase II study, gemcitabine and vinorelbine were combined at suboptimal doses for weekly administration in advanced non-small cell lung cancer (NSCLC). The primary objectives were to determine objective response rate (ORR) and time to progression (TTP). Secondary endpoints were safety and overall survival. Chemonaive patients with histologically or cytologically confirmed stage IIIB or IV NSCLC received vinorelbine (25 mg/m2) immediately followed by gemcitabine (800 mg/m2) once each week (on day 1) for 6 months without rest. From May 1998 to May 1999, 40 patients were enrolled (85% males; 70% stage IV) with a median age of 65.5. A total of 478 doses were administered, with a median of 9 per patient (range 2-72). The ORR was 27.5% (95% CI, 15.1-44.1%). The median TTP was 3.5 months (95% CI, 2.9-4.4 months). At a median follow-up of 6.5 months, the median survival was 11.6 months, and survival rates at 1 and 2 year(s) were 47.5% and 15.8%, respectively. The most common grade 3/4 hematologic toxicity was neutropenia, in 70% of patients, with febrile neutropenia in 28%. The most common grade 3/4 non-hematologic toxicity was transaminase elevation, in 22.5% of patients, which was transient and reversible. The other most prominent toxicities were, unexpectedly, pulmonary and cardiac toxicities. Based on these results, weekly, long-term administration of gemcitabine-vinorelbine appears to be an active regimen in NSCLC that warrants further investigation.     

Biweekly vinorelbine and gemcitabine: a phase I dose-finding study in patients with advanced solid tumors.

BACKGROUND: The purpose of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose of a combination of vinorelbine plus gemcitabine administered on a biweekly schedule in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with advanced or refractory solid tumors included in this phase I study were treated with vinorelbine followed by gemcitabine. Vinorelbine was given intravenously over 10 min, and gemcitabine was given intravenously at an fixed-dose infusion rate of 10 mg/m(2)/min. Six dose levels of vinorelbine/gemcitabine were explored: 20/2000, 25/2500, 25/3000, 30/3000, 30/3500 and 30/2500 mg/m(2). RESULTS: Nineteen patients were included in the study. Fourteen patients were pretreated with chemotherapy and/or radiotherapy. A total of 123 cycles of chemotherapy were administered. DLTs were neutropenic fever and grade 3 asthenia at dose level 5 (30/3500 mg/m(2)); at dose level 4 (30/3000 mg/m(2)) they were grade 3 asthenia, and a radiation-recall reaction and pneumonitis. Sixteen patients were evaluable for efficacy. Five patients had an objective response (one complete response and four partial responses), for an overall response rate of 31%. CONCLUSIONS: The recommended dose for phase II study is vinorelbine 30 mg/m(2) and gemcitabine 2500 mg/m(2) administered once every 2 weeks. This regimen is feasible and well-tolerated at this dose, and shows a good clinical activity in all levels explored.     

GP方案和NP方案治疗晚期NSCLC近期疗效比较

目的观察吉西他滨联合顺铂（GP方案）与长春瑞滨联合顺铂（NP方案）治疗晚期非小细胞肺癌（NSCLC）的疗效及毒副反应。方法对89例经病理或细胞学证实的晚期非小细胞肺癌患者给予联合化疗,GP方案49例,NP方案40例,两组病例具有可比性。吉西他滨1000 mg/m2,静脉滴注第1、8天;顺铂25 mg/m2,静脉滴注,第1~3天;长春瑞滨25 mg/m2,静脉滴注,第1、8天。21 d为一个周期,每例患者治疗2周期以上。结果 GP组总有效率46.9%,NP组总有效率42.5%,差异无显著性（P〉0.05）。最常见的毒副反应为骨髓抑制。GP组Ⅲ~Ⅳ度血小板减少发生率显著高于NP组（P〈0.05）,而NP组Ⅲ~Ⅳ度白细胞减少发生率显著高于GP组（P〈0.05）。静脉炎发生率NP组显著高于GP组（P〈0.05）。结论 GP方案与NP方案治疗晚期非小细胞肺癌（NSCLC）疗效肯定,毒性均可耐受。两方案疗效比较差异无显著性。     

Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial

BACKGROUND: Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC. METHODS: Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m(2) of body surface area), gemcitabine (1200 mg/m(2)), or vinorelbine (25 mg/m(2)) plus gemcitabine (1000 mg/m(2)). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test. Secondary endpoints were quality of life and toxicity. RESULTS: Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI] = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly. CONCLUSION: The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.     

NP和GP方案治疗晚期非小细胞肺癌疗效分析

目的:评价NP和GP两组化疗方案治疗晚期非小细胞肺癌(nonsmallcelllungcancer,NSCLC)的疗效和不良反应。方法:将有明确的病理学和(或)细胞学诊断的63例晚期NSCLC患者分为两组,NP组33例,国产长春瑞滨(盖诺,NVB)25mg/m2,静脉推注,d1、d8;顺铂(DDP)80～90mg/m2,静脉滴入,d1;GP组30例,吉西他滨(健择,GEM)1.25g/m2,静脉滴入,d1、d8;DDP80～90mg/m2,静脉滴入,d1。两组同时配合水化利尿,每21d为1个周期,化疗3个周期后评价疗效,化疗期间记录不良反应。结果:NP与GP方案的有效率分别为36.3%和40.0%,中位生存时间分别为12.2和12.0个月,1年生存率分别为47.2%和43.5%,2年生存率分别为21.1%和17.8%。不良反应主要为血液学毒性和恶心、呕吐。结论:NP和GP两组化疗方案在治疗晚期NSCLC的近期疗效、中位生存期、1年和2年生存率方面相近,化疗不良反应可耐受。     

Phase II study of gemcitabine and vinorelbine combination chemotherapy in patients with non-small-cell lung cancer not responding to previous chemotherapy

Both gemcitabine and vinorelbine are new anticancer drugs that have shown activity in the treatment of chemona?ve non-small-cell lung cancer (NSCLC). Their role in the second-line treatment of NSCLC is less clear. We conducted a phase II study of gemcitabine and vinorelbine combination chemotherapy in patients with NSCLC who had not responded to previous platinum-based chemotherapy, to assess the response and toxicity of this regimen. Seventeen patients were enrolled from September 1998 to February 2001. Treatment consisted of vinorelbine 20 mg/m2 and gemcitabine 800 mg/m2 intravenous infusion on days 1, 8, and 15 every 4 weeks. Sixty-five cycles of treatment were given, with a median of four cycles. All patients were evaluable for the toxicity profile, and 16 patients were evaluable for the response rate. The major toxicity was myelosuppression. Grade III or IV neutropenia occurred in 9 patients (52.9%) during treatment. Febrile neutropenia occurred in only 1 patient (5.9%). Grade III anemia and thrombocytopenia occurred in two and three patients, respectively. Other toxicities were few and mild in severity. After 2 cycles of treatment, 5 of 16 patients (31.3%) had a partial response (95% CI 8.6-64%). The median time to disease progression was 4.6 months and the median survival was 8.3 months. The 1-year survival rate was 34.3%. In conclusion, gemcitabine and vinorelbine salvage chemotherapy produces a relatively high response rate, low toxicity profile, and good survival in Chinese patients with NSCLC who have not responded to previous platinum-based chemotherapy. Further study is needed to confirm its activity.     

Vinorelbine and gemcitabine combinations in advanced non small-cell lung cancer

Several new chemotherapeutic agents were developed and tested in advanced non small-cell lung cancer (NSCLC) in the past decade. Vinorelbine and gemcitabine showed consistent single-agent activity in phase II and III trials and have been shown to be superior to older combinations when combined with cisplatin. However, toxicity associated with these regimens remains substantial, and nonplatinum alternatives are currently being explored. Based on the individual activity of vinorelbine and gemcitabine, their distinct mechanisms of action, and their mild, nonoverlapping toxicities, several trials evaluated their use in combination in patients with advanced NSCLC. Therapy has been administered in a convenient outpatient setting over a period of 1 hour. Different weekly schedules have been tested, but in general, toxicity is mild and the regimen is well tolerated, even in elderly patients or those with a poor performance status. Efficacy seems to be at least comparable to traditional platinum-based regimens, with respect to overall response rate and survival. In summary, vinorelbine/gemcitabine is an active and well-tolerated regimen and represents an option for the treatment of patients with advanced NSCLC. Randomized studies comparing this combination to reference platinum- or taxane-based regimens are needed to further evaluate the role of this combination in advanced NSCLC.     

Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group.

PURPOSE: To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m(2) + vinorelbine 25 mg/m(2) on days 1 and 8 + cisplatin 75 mg/m(2) on day 2 every 3 weeks). Primary end point of the study was overall survival. RESULTS: Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P =.73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P =.35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P =.004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. CONCLUSION: In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.     

Sequential chemotherapy of cisplatin and vinorelbine followed by paclitaxel and gemcitabine in advanced non-small-cell lung cancer. A single institution phase II study

BACKGROUND: To determine the activity and safety of a sequential regimen of cisplatin and vinorelbine followed by paclitaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Treatment was two cycles of cisplatin 80 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 3 weeks followed by two cycles of paclitaxel 175 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1 and 8 every 3 weeks. RESULTS: Fifty-five patients with inoperable NSCLC, performance status 2 or less were enrolled, including 19 patients with brain lesions. There were 23 partial responses (42%; 95% confidence interval 29-55). The median time to progression and overall survival were 5.8 and 10.3 months, respectively (6.5 and 12.8 in the patient subset without brain metastases). One-year survival rate was 47.5%. Grade III/IV neutropenia was the major side effect; it occurred in 56% of patients and was mainly limited to the first two chemotherapy cycles with cisplatin and vinorelbine. CONCLUSIONS: Sequential combination of cisplatin and vinorelbine followed by paclitaxel and gemcitabine is a manageable and active regimen for patients with NSCLC. It deserves to be tested against a standard two-drug scheme in a phase III trial.     

Gemcitabine and vinorelbine as second-line therapy in non-small-cell lung cancer after prior treatment with taxane+platinum-based regimens

Treatment options in patients with recurrent non-small-cell lung cancer (NSCLC) remain limited as a result of the poor activity of older agents after platinum-based therapy. The present phase II study aimed to evaluate the combination of gemcitabine and vinorelbine in patients with relapsed NSCLC after pretreatment with taxane+platinum-based regimens, since gemcitabine has demonstrated activity in that setting and the combination has been well tolerated in previous phase I/II studies. Patients with advanced NSCLC (stages III/IV), World Health Organization (WHO), Performance Status (PS) < or = 2, prior platinum+taxane-based chemotherapy and unimpaired haematopoietic and organ function were eligible. Chemotherapy was administered as follows: vinorelbine 25 mg/m(2) followed by gemcitabine 1000 mg/m(2), both administered on days 1 and 8, recycled every 3 weeks. 40 patients were entered and 39 were evaluable for response and all 40 for toxicity: median age was 61 years (range 50-72 years), median PS=1 (range 0-2), gender ratio=37 males/3 females, stages at initial diagnoses were IIIA=2, IIIB=14, IV=24. Metastatic sites included: lymph nodes: 23, bone: 4, liver: 5, brain: 4, lung nodules: 9, adrenals: 8, pleural effusion: 4. 22 patients had prior paclitaxel/ifosfamide/cisplatin treatment. Objective responses were; partial response (PR): 9/40 (22.5%), stable disease (SD): 13/40 (32.5%) and progressive disease (PD) 18/40 (45%). The median time-to-progression (TTP) was 4.5 months (range 1-17 months) and median survival 7 months (range 2-17+ months). 1-year survival was 17%. Grade 3 neutropenia was seen in 33% of patients. There was no grade 4 neutropenia and no episodes of febrile neutropenia. No grade 3/4 thrombocytopenia or grade 3/4 other non-haematological toxicities were observed. The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC failing prior taxane/platinum therapy. This regimen represents a tolerable and effective combination to apply in the palliative treatment of relapsed NSCLC.     

Vinorelbine/gemcitabine in advanced non-small cell lung cancer (NSCLC): a phase I trial

Vinorelbine and gemcitabine are both active as single agents in advanced non-small cell lung cancer (NSCLC). Because of their different mechanisms of action, good tolerability and possible administration on an out-patient basis, vinorelbine/gemcitabine should be an interesting combination for palliative chemotherapy. Thus, we initiated a phase I dose-escalation trial in order to determine the maximum tolerated doses of vinorelbine/gemcitabine that can be administered without haematopoietic growth factors, the dose-limiting toxicities and the most frequent side-effects of this novel combination. 40 chemotherapy-na?ve patients with advanced NSCLC were treated with different doses of vinorelbine/gemcitabine on days 1, 8 and 15, and this treatment cycle was repeated on day 29. Vinorelbine and gemcitabine were escalated from 10 to 30 mg/m2 and 600 to 1200 mg/m2, respectively. A total of 63 treatment cycles were administered and 27 patients received at least two treatment cycles. Dose-limiting toxicities were leucopenia plus thrombocytopenia (2 patients) and mucositis (1 patient). The maximum tolerated dose was established at 25 mg/m2 vinorelbine combined with 1200 mg/m2 gemcitabine. Frequent side-effects were leucopenia, anaemia, nausea/vomiting, flu-like symptoms, skin rashes and elevation of liver enzymes. The recommended phase II doses are 20-25 mg/m2 vinorelbine combined with 1000-1200 mg/m2 gemcitabine on days 1, 8 and 15, but myelosuppression will have to be carefully monitored.