Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.     

Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer

This study compares two cytotoxic regimens comprising the same dose and schedule of cisplatin (CP) plus vinorelbine (VNR) or gemcitabine (GEM) administered under the same schedule to patients with advanced non-small cell lung cancers (NSCLC). From April 1998 to February 2003, 285 patients were randomised to receive either VNR 25 mg/m(2) on days 1 and 8 as an intravenous (i.v.) bolus plus CP 75 mg/m(2) on day 1 (regimen A) or GEM 1200 mg/m(2) on days 1 and 8 as an i.v. 30-min infusion plus CP 75 mg/m(2) on day 1 (regimen B). Both treatments were recycled every 21 days. If no progression had occurred after six cycles, the patients continued to receive VNR or GEM monochemotherapy weekly. Cross-over of the two single agents was considered if disease progression occurred. Objective response (OR), time to progression (TTP) and overall survival (OS) were analysed according to the intention-to-treat principle. 272 patients were ultimately eligible (137 on A and 135 on B). Their main characteristics were: male/female ratio 214/58; median age 63 (range 32-77) years; median Karnofsky Performance Status (PS) 80 (range 70-100); stage IIIB 34%, stage IV 61%, recurrent disease 5%; histology - epidermoid 29%, adenocarcinoma 53%, other NSCLC 18%. The characteristics of the patients in the two arms were well matched. The following response rates were observed in regimens A and B, respectively: complete response (CR) 0.7% and 3.7%, partial response (PR) 31.9% and 22.2% (P = 0.321). Median CR+PR duration was 8 months in both arms. Clinical benefit represented by an improvement in symptoms was evident in 25.7% and 28.1%, respectively. Median TTP was 5 months in both arms and median OS 11 months in both arms. Grade III-IV neutropenia occurred in 30.7% and 17.7% of the patients in arms A and B, respectively (P = 0.017); thrombocytopenia occurred in 0% and 9.3% (P = 0.004), respectively. No difference in the incidence of anaemia was observed. Non-haematological toxicity was generally mild: a higher incidence of grade 1-2 peripheral neurotoxicity and grade 1-2 local toxicity with regimen A and grade 1-2 liver toxicity with regimen B was reported. A pharmaco-economic comparison showed a difference between the two doublets, principally due to the different costs of VNR and GEM. Under the study conditions the combination of VNR or GEM with the same dose and schedule of CP produced similar OR, clinical benefits, TTP and OS in advanced NSCLC, and only mild toxicological differences were observed. Pharmaco-economic evaluation favoured the CP + VNR doublet.     

Gemcitabine and vinorelbine followed by docetaxel in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02)

To evaluate the efficacy and toxicity of the sequential nonplatinum combination chemotherapy consisting of gemcitabine (GEM) and vinorelbine (VNR) followed by docetaxel (DOC) in patients with advanced non-small-cell lung cancer (NSCLC), we conducted the multiinstitutional phase II study. A total of 44 chemotherapy-naive patients with advanced NSCLC were treated with GEM 1000 mg m(-2) and VNR 25 mg m(-2) intravenously on days 1 and 8 every 3 weeks for three cycles. DOC 60 mg m(-2) was then administrated intravenously at 3-week intervals for three cycles. Patients were evaluated for response and toxicity with each cycle of the treatment. The major objective response rate was 47.7% (95% confidence interval (CI), 33.8-62.1%). Median survival time (MST) was 15.7 months and 1-year survival rate was 59%. In the GEM/VNR cycle, grade 3/4 neutropenia occurred in 36.3%, grade 3/4 anaemia in two patients (4.5%) and grade 3 thrombocytopenia in one patient (2.3%). Grade 3 pneumonitis occurred in two patients (4.5%) in GEM/VNR cycles. In the DOC cycles, grade 3/4 neutropenia occurred in 39.4% but no patient experienced grade 3/4 anaemia or thrombocytopenia. Of the 44 eligible patients, 33 patients completed three cycles of GEM/VNR and 22 patients completed six cycles of planned chemotherapy (three cycles of GEM/VNR followed by three cycles of DOC). The sequential triplet nonplatinum chemotherapy consisted of GEM/VNR followed by DOC, and was very active and well tolerated. This study forms the basis for an ongoing phase III trial that compares this nonplatinum triplet and standard platinum doublet combination (carboplatin/paclitaxel).     

Bi-weekly administration of gemcitabine plus vinorelbine in elderly patients with advanced non-small-cell lung cancer: multicenter phase II trial

PURPOSE: Gemcitabine (GEM) and vinorelbine (VNR) have demonstrated activity as a first-line treatment in elderly patients with advanced non-small-cell lung cancer (NSCLC). We conducted a multicenter phase II trial to evaluate the efficacy and toxicity of bi-weekly administration of GEM plus VNR in elderly patients with advanced NSCLC. PATIENTS AND METHODS: Forty-six chemotherapy-naive elderly (age: >or=70 years) NSCLC patients were enrolled. Patients were eligible if they had histologically or cytologically confirmed unresectable NSCLC with measurable and/or assessable disease. Patients received GEM (1000 mg/m2) and VNR (25 mg/m2) every 2 weeks. RESULTS: The objective response rate of this treatment was 22.7% (95% confidence interval (CI), 10.3-35.1%), median survival time was 310 days, and median time to progression was 133 days. The one-year survival rate was 40.9% (95% CI, 26.3-55.4%), and most adverse events were mild. Only three (6.8%) patients needed to omit GEM because of grade 4 neutropenia or due to physician judgment. No patients suffered treatment-related death. CONCLUSIONS: Bi-weekly administration of GEM plus VNR in elderly patients was an effective, feasible and well-tolerated treatment schedule.     

Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): a multicentre phase II clinical trial

A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37-73) and a median ECOG performance status of 1 (range 0-2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m(2) diluted in 250 cc(3) of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m(2) on days 1 and 8 every 4 weeks. The median number of courses/patient was 4 (range 3-7). According to an intent-to-treat analysis 2 (4%) patients had a complete response and 16 (36%; 95% CL 22-52%) had a partial response for an overall response rate of 40% (95% CL 26-56%). Twelve (27%) patients had stable disease and 15 (33%) were considered as treatment failures. Median overall survival of the whole series was 8+ months with 33% of patients alive at 1 year. Toxicity was generally mild. WHO grade 3-4 neutropenia was recorded in 22% of cases, grade 1-3 liver toxicity in 6% of patients and neutropenia-unrelated fever in 9%. This multicentre phase II study suggests that the GEM/VNR combination regimen is an active and well tolerated regimen in patients with stage IIIB/IV NSCLC. Larger studies comparing cisplatin-based regimens to new schedules without cisplatin are warranted.     

Functional polymorphisms of the microsomal epoxide hydrolase gene: a reappraisal on a early-onset lung cancer patients series

As concomitant chemoradiotherapy for stage III NSCLC is associated with survival advantage in comparison to a sequential approach, we conducted a phase III randomised study aiming to determine the best sequence and safety of chemotherapy (CT) and chemoradiotherapy (CT-RT), using a regimen with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR). Unresectable stage III NSCLC patients received CDDP (60 mg/m(2)), GEM (1g/m(2), days 1 and 8) and VNR (25mg/m(2), days 1 and 8) with reduced dosage of GEM and VNR during radiotherapy (66Gy). Two cycles of CT with radiotherapy followed by two further cycles of CT alone were administered in arm A or the reverse sequence in arm B. The study was prematurely closed for poor accrual due to administrative problems. Forty-nine eligible patients were randomised. Response rates and median survival times were, respectively 57% (95% CI: 36-78%) and 17 months (95% CI: 9.3-24.6 months) in arm A and 79% (95% CI: 64-94%) and 23.9 months (95% CI: 13.3-34.5 months) in arm B (p>0.05). Chemotherapy dose-intensity was significantly reduced in arm A. Grade 3-4 oesophagitis occurred in 5 patients. One case of grade 5 radiation pneumonitis was observed. In conclusion, chemoradiotherapy with CDDP, GEM and VNR appears feasible as initial treatment or after induction chemotherapy. Consolidation chemoradiotherapy seems less toxic with a better observed response rates and survival although no valid conclusion can be drawn from the comparison of both arms.     

Cisplatin, gemcitabine and vinorelbine in locally advanced or metastatic non-small-cell lung cancer: A phase I study

Purpose: The objective of this study was to determine the maximally tolerable doses (MTDs) of vinorelbine (VNR) and gemcitabine (GEM) when combined with a fixed dose of cisplatin (CDDP).Patients and methods: Chemotherapy-naïve patients with stage IIIB–IV non-small-cell lung cancer (NSCLC) received a fixed dose of CDDP (50 mg/m²) and escalating doses of VNR (starting from 20 mg/m²) and GEM (starting from 800 mg/m²) on days 1 and 8, every three weeks. The single escalation of GEM alone, by 200 mg/m² at each step, was initially planned up to a dose of 1,200 mg/m², to be followed by increments of the VNR dose of 5 mg/m² at each step.Results: Thirty-one patients were enrolled at five different dose levels. The escalation was stopped at level 4 (GEM 1,200 mg/m² and VNR 25 mg/m²) since two of six patients of this cohort showed dose-limiting neutropenia at treatment cycle 1. Two different dose levels, GEM 1,200 mg/m² + VNR 20 mg/m², and GEM 1,000 mg/m² + VNR 25 mg/m², were fairly well tolerated. No treatment-related deaths occurred. Neutropenia was the main toxic effect, occurring in 76% of the total of 116 cycles delivered, and in 24% of them was of grades 3 or 4. A total of eight patients (26%) experienced grade 4 neutropenia lasting more than seven days; in five of them it occurred in the first course. Neutropenic fever was observed in four cases. Grade 4 thrombocytopenia occurred in only two patients. Non-hematologic toxicity was a minor problem in all patients but was never dose-limiting. No complete responses were obtained, but sixteen out of 31 (52%) patients achieved partial responses. The median duration of response was 20 (range 6–56+) weeks, while at a nine-month median follow-up, the median survival time has not yet been reached. To date, 18 patients are still alive. The one-year projected survival for all patients was 51%.Conclusions: Our results show that CDDP, VNR and GEM can be safely given together without substantial reductions in their individual dose intensities. In our opinion, the dose level of GEM 1,000 mg/m² + VNR 25 mg/m² given in combination with CDDP 50 mg/m² on days 1 and 8 of a three-week cycle can be recommended for phase II trials, since it provides a better balance in dose intensity of GEM and VNR. A phase II randomised study is underway to establish the activity of this new regimen (at the above-cited dose level) in chemo-naïve NSCLC patients.     

Phase II study of weekly chemotherapy with paclitaxel and gemcitabine as second-line treatment for advanced non-small cell lung cancer after treatment with platinum-based chemotherapy

Purpose We evaluated the tolerability and activity of the combination of weekly paclitaxel (PTX) and gemcitabine (GEM) in second-line treatment of advanced non-small cell lung cancer (NSCLC) after treatment with platinum-based chemotherapy. Patients and methods PTX (100 mg/m²) and GEM (1,000 mg/m²) were administered to patients with previous treated NSCLC on days 1 and 8 every 3 weeks. Results A total of 40 patients (performance status 0/1/2, 7/27/6 pts) were enrolled. The response rate was 32.5% (95% confidence interval: 18.0–47.0%). The median survival time was 41.7 weeks (95% confidence interval: 28.5–54.7 weeks). The median time to disease progression was 19 weeks. Hematological toxicities (grade 3 or 4) observed included neutropenia in 60%, anemia in 15%, and thrombocytopenia in 12.5% of patients. Non-hematological toxicities were mild, with the exception of grade 3 diarrhea, pneumonitis, and rash in one patient each. There were no deaths due to toxicity. Conclusion The combination of weekly PTX and GEM is a feasible, well-tolerated, and active means of second-line treatment of advanced NSCLC.     

A phase II trial of weekly paclitaxel and gemctiabine infused at a constant rate in patients with advanced non-small cell lung cancer

BACKGROUND: Gemcitabine and paclitaxel both have significant single agent activity in non-small cell lung cancer (NSCLC). Because both are cell cycle and phase specific in their mechanism of action, frequent exposure should optimize activity. Phase I data support that gemcitabine is maximally converted to the active metabolite when it is infused at a rate of 10 mg/(m2 min). Based on this, we designed a phase II trial to examine gemcitabine 800 mg/m2 infused over 80 min with paclitaxel 110 mg/m2 infused over 3 h both on days 1, 8 and 15 every 28 days as first line therapy in patients with advanced NSCLC. The primary objectives were to assess the response rate, toxicity and survival of the combination in advanced NSCLC. Secondary objectives were to determine the effect of paclitaxel on the pharmacokinetic (PK) distribution of gemcitabine, the ability to achieve a concentration of 10-20 microM when gemcitabine was infused at a rate of 10 mg/(m2 min), as well as to assess the quality of life (QOL) with the functional assessment of cancer therapy-lung (FACT-L) questionnaire. METHODS: Patients with NSCLC, no prior treatment, ECOG performance status (PS) 0-1, adequate bone marrow, renal, and hepatic function were eligible for this trial. Paclitaxel 110 mg/m2 was infused over 3 h, followed by gemcitabine 800 mg/m2 infused over 80 min on days 1, 8, and 15 every 28 days for the first 2 patients, and then amended to days 1 and 8 every 21 days after the first 2 patients required day 15 dose omissions due to myelosupression. RESULTS: Thirty-nine patients were treated. Nine PS = 0; 28 PS = 1; Stage IIIB = 3, Stage IV = 36; median age 62 (range: 39-77). A median of six cycles (range: 0-10) was delivered. Grade 3-4 toxicities observed in > or =10% of patients included leucopenia in 26%, neutropenia in 28%, dyspnea in 13%, febrile neutropenia in 3% (1 patient). Fourteen of 39 (35%, 95% CI: 21-53%) patients had a partial response (PR), 14 of 39 (35%, 95% CI: 21-53%) had stable disease (SD) and 5 patients (13%, 95% CI: 4-27%) had progressive (PD). Median survival was 10.4 months (95% CI: 5.3-13.6). One-and two-year survival rates were 35% (95% CI: 21-53%) and 5% (95% CI: 0.6-17%), respectively. QOL as measured by the FACT-L and the trial outcome index (TOI) did not change significantly from baseline over the course of therapy. CONCLUSIONS: Paclitaxel and gemcitabine is an active and well-tolerated combination in advanced NSCLC. Patients on this trial had no significant change in their QOL as assessed by the FACT-L questionnaire.     

A phase II study of biweekly paclitaxel (P) and gemcitabine (G), followed by maintenance weekly paclitaxel in elderly patients with advanced non-small cell lung cancer (NSCLC)

BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of a novel combination of paclitaxel (P) and gemcitabine (G) in an every 2 weeks schedule followed by weekly paclitaxel (P) as first-line treatment in elderly patients with locally advanced or metastatic NSCLC. METHODS: Elderly patients (> or =65 years of age) with 1997 TNM stage IIIB (pleural effusion)/stage IV NSCLC, performance status (PS) of 0-2 and normal organ function were eligible. Therapy consisted of P at 150 mg/m(2) and G at 2000 mg/m(2) administered every 2 weeks for 3 cycles followed, in progression-free patients, by P at 80 mg/m(2) every week for 6 consecutive weeks every 8 weeks for 2 cycles. RESULTS: Fifty-three eligible patients were enrolled: M/F 51/2; stage IIIB/IV 8/45; PS 0, 40%, PS 1 51%, PS 2 9%; median age, 73 years (range 67-82). The overall response rate was 32% (95% confidence interval [CI]: 19-45). The median overall survival was 7 months (95% CI: 5-9); the median progression-free survival was 5 months (95% CI: 3-6); and the 1- and 2-year survivals were 28.3% and 10.1%, respectively. Both phases of the treatment protocol were well tolerated. CONCLUSIONS: Biweekly P/G followed by weekly P is well tolerated and active as first-line therapy for elderly NSCLC patients.     

Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial

PURPOSE: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy. PATIENTS AND METHODS: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm). RESULTS: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities. CONCLUSION: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.     

Cisplatin, gemcitabine, and vinorelbine combination therapy in advanced non-small-cell lung cancer: a phase II randomized study of the Southern Italy Cooperative Oncology Group.

PURPOSE: In a previous phase I study cisplatin (CDDP), gemcitabine (GEM), and vinorelbine (VNR) combination therapy was safe and very active in patients with non-small-cell lung cancer (NSCLC). This study was aimed at better defining the activity and toxicity of this regimen. PATIENTS AND METHODS: One hundred eleven chemotherapy-naive patients, age < or = 70 years, with stage IIIB or IV NSCLC and a performance status of 0 or 1 (Eastern Cooperative Oncology Group scale) were randomized to two treatment arms. Patients on arm A received CDDP 50 mg/m2, GEM 1,000 mg/m2, and VNR 25 mg/m2 on days 1 and 8 of an every-3-weeks cycle (57 patients). Patients on arm B received CDDP 80 mg/m2, epirubicin 80 mg/m2, and vindesine 3 mg/m2, all delivered on day 1 every 4 weeks, plus lonidamine orally 150 mg three times daily (54 patients). In December 1996, randomization was stopped early, and an additional 30 patients were treated with the experimental regimen to obtain a more accurate estimation of its activity rate. RESULTS: Among 87 patients who received the CDDP-GEM-VNR combination, four complete responses (CRs) and 46 partial responses (PRs) were observed, for an overall response rate of 57% (95% confidence interval [CI], 46% to 68%). Two CRs and 18 PRs were recorded among 54 patients on arm B, giving a 37% activity rate (95% CI , 24% to 51%). After a median follow-up duration of 19 months, the median progression-free and overall survival durations were 32 and 50 weeks in arm A, and 18 and 33 weeks in arm B, respectively. World Health Organization grade 3 to 4 neutropenia and thrombocytopenia occurred in 46% and 14% of patients in arm A and in 22% and 11% of those in arm B, respectively. Severe nonhematologic toxicity was uncommon in both arms. CONCLUSION: The CDDP-GEM-VNR combination is a highly effective treatment for patients with advanced NSCLC and has a manageable toxicity. A phase III trial comparing this new combination with both CDDP-VNR and CDDP-GEM regimens is underway.     

Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) 0104

BACKGROUND: Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. METHODS: One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. RESULTS: Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). CONCLUSIONS: Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study.     

Intra-patient alternated dose escalation of paclitaxel and gemcitabine versus paclitaxel followed by fixed dose rate infusion of gemcitabine in fit elderly non-small cell lung cancer patients. A Southern Italy Cooperative Oncology Group randomised phase II trial

PURPOSE: This study was undertaken to select the best schedule of administration for the paclitaxel plus gemcitabine combination in fit elderly patients affected by locally advanced or metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-eight patients in stage III or IV NSCLC, aged 70 years or more and in ECOG performance status (PS)相似文献   

Combination therapy with vinorelbine and gemcitabine in unresectable non-small cell lung cancer

Vinorelbine (VNR) and gemcitabine (GEM) were used in combination to treat 10 patients with unresectable non-small cell lung cancer to study the efficacy, safety, possibility of out-patient administration, and improvement of subjective symptoms. One course of treatment consisted of i.v. drip infusion of VNR at 25 mg/m2 followed by i.v. drip infusion of GEM at 1,000 mg/m2 on day 1 and day 8. This course was repeated more than twice, as a rule, at 3-week intervals. In 10 patients registered from November 1999 to March 2000, we observed PR in 5, SD in 4 and PD in 1. The response rate was 50%. PS was improved in 5 out of 6 patients with PS 1 or worse. All 4 patients with subjective symptoms reported improvement. Adverse effects of leukopenia of grade 3 or more occurred in 50% of patients and neutropenia in 80%. By dose reduction, we could administer 7.1 courses to each patient on average. Non-hematological toxicities, excluding eruption of grade 3 which occurred in the first course and made it impossible to continue the treatment, were phlebitis in 40% of patients, anorexia in 30% (only grades 1 and 2) and transient drug fever (only grade 1) in 50%. All were tractable, and no lung toxicity occurred. Antibiotic chemotherapy could be performed in 7 patients on an outpatient basis. Combination therapy with VNR and GEM also seemed to be a safe and useful treatment on an outpatient basis.     

A phase II study of weekly paclitaxel for advanced or recurrent breast cancer

The present study investigated the efficacy and safety of weekly administration of paclitaxel (PTX) for 37 patients with advanced or recurrent breast cancer. PTX was administered at a dose of 60 mg/m(2), 6 times every 8 weeks. The mean number of treatment cycles was 2.1, and the mean number of administrations was 12.7. Response rate was 35.1%. Two patients achieved CR, 11 PR, 13 NC (3 patients of long NC), 9 PD, and 2 NE. The clinical benefit rate (CR+PR+NC) was 70.3%. Median survival time was 733 days, and median time to treatment failure was 151 days. Grade 3 or more leucopenia and neutropenia occurred in 3 of patients (8.1%), and no patients showed hypersensitivity reaction after administration of PTX. Weekly PTX (60 mg/m(2)) is one of the treatment options in advanced or recurrent breast cancer from the standpoint of palliation.     

Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is expected to increase due to delayed control of occupational exposure to asbestos in Japan. We investigated the use of triplet combination chemotherapy with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR) for the treatment of Japanese patients with MPM. METHODS: From December 2000 to August 2003, 12 patients received the following regimen: CDDP 40 mg/m(2), GEM 800 mg/m(2) and VNR 20 mg/m(2) on days 1 and 8 every 4 weeks. Among the 12 patients, six selected patients underwent an extrapleural pneumonectomy (EP) after a median of three cycles of triplet chemotherapy. RESULTS: The overall response rate for all patients and the response rate for chemotherapy-naive cases were 58 and 67%, respectively. The median survival time and survival rate at 2 years for all patients were 11 months and 50%, respectively. The 2-year survival rates for the patients with and without EP were 83.3 and 16.7%, respectively. CONCLUSIONS: Triplet chemotherapy with CDDP, GEM and VNR was thus found to be highly effective for patients with MPM and its toxicity was manageable. A multi-institutional phase II trial is now being planned to establish the effectiveness of this new regimen in chemotherapy-naive patients with MPM.     

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.     

紫杉醇加顺铂治疗晚期非小细胞肺癌的临床疗效

目的 观察紫杉醇(PTX)加顺铂(DDP)联合化疗治疗晚期非小细胞肺癌的近期疗效。方法 PTX135～180mg／m^2静脉滴注，第1天；DDP40mg／次，静脉滴注，第1～3天。每21天为一个周期，连用2或3周期。结果 可评价疗效者46例．其中CR1例(2．2％)，PR16例(34．8％)，总有效率为37．0％。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，是个较好的联合化疗方案。     

Sequential combination chemotherapy in patients with advanced nonsmall cell lung carcinoma: carboplatin and gemcitabine followed by paclitaxel.

BACKGROUND: The objective of this Phase II study was to evaluate the concept of sequential chemotherapy in the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC) by the administration of carboplatin plus gemcitabine followed by of paclitaxel. METHODS: Patients with Stage IIIB (pleural effusion) or Stage IV NSCLC and a Southwest Oncology Group (SWOG) performance status (PS) of 0--2 were eligible. Therapy consisted of three cycles of carboplatin (area under the concentration-time curve = 5.5 mg/mL per minute) on Day 1 and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days followed by three cycles of paclitaxel 225 mg/m(2) every 21 days. RESULTS: Of the 37 eligible patients, 81% had Stage IV disease, and 27% had a PS of 2; all were assessable for survival and toxicity; 32 patients were assessable for response. After treatment with carboplatin plus gemcitabine, there were no complete responses (CRs) and eight partial responses (PRs) (response rate [RR], 25%; 95% confidence interval [95% CI], 11--43%). The best overall response was two CRs and eight PRs (RR, 31%; 95% CI, 16--50%). The median survival time was 9.5 months, the 1-year survival rate was 36% (95% CI, 26--44%), the 2-year survival rate was 11% (95% CI, 3--25%), and the median time to disease progression was 4.9 months. The median survivals were 11.2 months for patients with a PS of 0--1 and 6.4 months for patients with a PS of 2. Noncumulative, reversible thrombocytopenia was the principal toxicity with carboplatin/gemcitabine therapy. Paclitaxel therapy was well tolerated, and moderate (Grade 3) neutropenia was the primary toxic effect. One cardiac death occurred, possibly related to paclitaxel. CONCLUSIONS: This study is the first to evaluate planned sequential chemotherapy in patients with NSCLC. Carboplatin plus gemcitabine followed by paclitaxel was well tolerated and resulted in promising survival in this patient population. This pilot experience forms the basis for an ongoing SWOG trial. Cancer 2001;92:146-52. Published 2001 American Cancer Society.