Phase I–II study of gemcitabine and paclitaxel in pretreated patients with stage IIIB–IV non-small cell lung cancer (original) (raw)
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Lung Cancer, 2000
Background: The combination of paclitaxel (P) and carboplatin (C) is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active new drug. We planned a phase I study to find the maximum tolerated dose (MTD) of the PCG combination. A phase II study was subsequently conducted to evaluate the activity and toxicity of PCG. Patients and methods: Forty-five patients entered the study. Twenty-eight had stage IIIA-B disease, 17 stage IV. In the phase I study, with a fixed dose of C at AUC = 6 on day 1, P was escalated using increments of 25 mg/m 2 starting from 175 mg/m 2 on day 1 and G with increments of 200 mg/m 2 starting from 800 mg/m 2 on day 1 and 8. Results: Fourteen patients entered the phase I study. The MTD was reached at P 200 mg/m 2 , C AUC = 6 and G 1000 mg/m 2. Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities. Thirty-one patients were treated in the phase II study with P 175 mg/m 2 , C AUC = 6 and G 1000 mg/m 2. Response rate was 57% (68% in stage III and 47% in stage IV). Myelosuppression was the main toxicity, with grade 3-4 leukopenia occurring in 35% of cases. Grade 3 anemia was observed in 24% of cases and grade 3-4 thrombocytopenia occurred in 34% of patients. Non-hematological toxicity was mild. Median survival and one-year actuarial survival were 20.5 months and 74% for stage III and 11.5 months and 47% for stage IV. Conclusions: PCG is a promising regimen for treating advanced NSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin in advanced NSCLC is ongoing. On the other hand, we are planning to introduce the PCG regimen in the treatment of stage II-III patients in the setting of a multimodality treatment.
Asian Pacific journal of cancer prevention : APJCP, 2012
The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine 1500 mg/m2 and paclitaxel 150 mg/m2 administered every two weeks. Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4...
A phase I-II study of gemcitabine and paclitaxel in advanced non-small-cell lung cancer patients
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2000
Thirty patients with chemotherapy-naïve advanced non-small-cell lung cancer (NSCLC) were given escalating doses of paclitaxel (150, 175, 200 mg/m2) on day 1 in three consecutive cycles, together with a fixed dose of gemcitabine 1000 mg/m2 on days 1 and 8; cycles were repeated every three weeks. The dose escalation of paclitaxel was feasible in the majority of patients. Subsequently, 30 other NSCLC patients received a dose of 200 mg/m2 paclitaxel with gemcitabine 1000 mg/m2 in a phase II study. The major side effect was mild myelosuppression. A response rate of 24% was achieved in 49 fully evaluable patients. This regimen proved to be safe and easy to administer on an out-patient setting, and constitutes now one of the arms of the current EORTC randomized study for advanced NSCLC.
Annals of Oncology, 2006
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/m 2 infused >30 min on days 1 and 8 and paclitaxel 200 mg/m 2 infused >3 h on day 1 of a 21-day cycle or Arm B (weekly): gemcitabine 1000 mg/m 2 infused >30 min and paclitaxel 100 mg/m 2 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 twofold 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.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2000
Gemcitabine (GEM) and paclitaxel (TAX) are active, non-cross-resistant drugs in non-small-cell lung cancer (NSCLC). We performed a phase I study to determine the maximum-tolerated dose (MTD), antitumor activity and pharmacokinetics of GEM and TAX given weekly in chemo-naïve patients with advanced NSCLC. Escalating doses of GEM (800-2000 mg/m2) and TAX (60-100 mg/m2) were administered on days 1, 8, 15 every 4 weeks to 35 patients with advanced NSCLC. Plasma pharmacokinetics of TAX and GEM was assessed at the three higher dose-levels. Dose-escalation was discontinued in absence of MTD because of increased cumulative toxicity leading to dose modification or treatment delay at levels 6 and 7 (TAX 100 mg/m2 plus GEM 1750 and, respectively, 2000 mg/m2). Hematological toxicity included grade 4 neutropenia in 3% of cycles, grade 3 thrombocytopenia in one cycle and febrile neutropenia in three cycles. Maximal non-hematological toxicity was grade 3 elevation in serum transaminases and grade 2...
Anticancer Research, 2004
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/m 2 on days 1, 8 and 15 and gemcitabine 1000 mg/m 2 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. Non-small cell lung cancer (NSCLC) represents a major health problem in Western countries (1). Currently, cisplatinor carboplatin-based therapy is considered the standard treatment for patients with advanced disease (2). Randomized clinical trials and a meta-analysis have shown that, when compared with supportive care, platinum-based regimens significantly prolong survival and provide relief of symptoms and improved quality of life (3,4). However, the benefit from combination chemotherapy still remains modest, since an important proportion of advanced NSCLC patients fail to respond to front-line treatment, while the remaining patients are likely to relapse after an initial response. Until recently, few patients who progressed on first-line therapy went on to receive subsequent chemotherapy. However, as newer and more effective chemotherapy agents become available, this situatiion is changing. Of the second generation agents that have been tested in previously treated NSCLC, docetaxel appears the most promising. It is the only agent to have been studied in randomised phase III trials (5,6) and it is the only currently approved therapy for treatmentrefractory NSCLC patients in Europe. Paclitaxel as a single agent or in combination has been repeatedly found to be active in previously untreated NSCLC patients, with response rates ranging from 10% to 38% and median survival ranging from 6 to 11 months (7). This drug has not been systematically studied in a secondline setting and the available data are conflicting (8). An important clinical issue regarding paclitaxel is the optimal schedule. Preclinical evaluation has shown that frequent administration of paclitaxel provides better therapeutic effects than delayed schedules (9,10). This dose-dense approach may inhibit tumor re-growth between cycles and enhance the apoptotic and antiangiogenetic effects of the drug (11,12). Preliminary experience of weekly paclitaxel administered to NSCLC patients suggests that this schedule is not only effective and well-tolerated, but is also able to maintain the planned dose intensity (13). In a recently published prospective randomized phase II trial involving NSCLC patients previously treated with platinum-based 2567
2007
The therapy for patients with advanced non-small-cell lung cancer (NSCLC) has improved in the past decade. Median survival and the 1-year survival have increased to 8-10 months and 35%-40%, respectively, and a minority of patients are surviving for 2 years (15%-20%) and 3 years (5%-10%). Platinum agentbased cytotoxic treatment has been the standard, but in recent years, other combinations of newer third-generation cytotoxic drugs have been compared with platinum agent-based regimens in an attempt to improve activity and/or decrease toxicity. Several recently reported trials do not show any advantage in efficacy for nonplatinum agent-based treatment. 1-5 However, there appears to be some toxicity advantages. In a large metaanalysis of 37 randomized studies that included 7633 patients and evaluated platinum agent-based versus nonplatinum agent-based chemotherapy, there was a significantly higher response rate (RR) for platinum agent-containing regimens; however, the 1-year survival was not significantly prolonged, and the toxicity Abstract PURPOSE: This prospective randomized study compared overall survival (OS) in patients with previously untreated advanced non-small-cell lung cancer (NSCLC) when treated with the platinum agent-based triple drug combination of paclitaxel/carboplatin/gemcitabine (PCG) versus the nonplatinum agent-based doublet drug combination of gemcitabine/vinorelbine. PATIENTS AND METHODS: Advanced (stages IIIB, IV, and recurrent) chemotherapynaive patients with NSCLC and performance status 0-2 were randomly assigned to the PCG arm (paclitaxel 200 mg/m 2 on day 1, carboplatin area under the concentration-time curve of 5 on day 1, and gemcitabine 1000 mg/ m 2 on days 1 and 8, every 21 days) or to the gemcitabine/vinorelbine arm (gemcitabine 1000 mg/m 2 on days 1, 8, and 15 and vinorelbine 25 mg/m 2 on days 1, 8, and 15, every 28 days). RESULTS: A total of 337 patients were randomly assigned to the 2 arms. The median time to progression was 6 months for PCG and 3.9 months for gemcitabine/vinorelbine with 1-and 2-year progression-free survival rates of 13% and 2% versus 14% and 4% (P = .324 log rank). Median OS for PCG was 10.3 months versus 10.7 months for gemcitabine/vinorelbine with 1-, 2-, and 3-year OS rates of 38%, 12%, and 2% versus 45%, 12%, and 6%, respectively (P = 0.269 log rank). Grade 3/4 thrombocytopenia, nausea/vomiting, myalgia/arthralgia, and neuropathy were significantly greater in the PCG arm. CONCLUSION: There was no difference in OS or progression-free survival when comparing PCG and gemcitabine/vinorelbine, and gemcitabine/vinorelbine was significantly less toxic. Gemcitabine/vinorelbine is a reasonable nonplatinum agent-based doublet therapy for patients with advanced NSCLC.