Paclitaxel and carboplatin in combination with gemcitabine (PCG): A phase I–II trial in advanced non-small cell lung cancer (NSCLC) (original) (raw)
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Lung Cancer, 2000
Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I -II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m 2 on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m 2 on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m 2 ; the paclitaxel dose level just below (210 mg/m 2 ) was selected for phase II evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23 -57%). Median duration of response was 35 weeks (range, 8-102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8 -108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely warranted.
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.
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
Clinical cancer research : an official journal of the American Association for Cancer Research, 1997
This Phase I study was designed to determine the maximally tolerated doses of paclitaxel (given as an outpatient 3-h infusion) plus carboplatin in advanced, untreated non-small cell lung cancer. Secondary objectives were to determine the response rate, response duration, and survival. Fifty-six patients were accrued, and all were evaluable for toxicity; 50 patients were assessable for response. Paclitaxel doses ranged from 135-250 mg/m2, whereas carboplatin dosing started at 250 mg/m2 and was escalated to 400 mg/m2. Patients received therapy on day 1 every 21 days for a maximum of six cycles. Prophylactic granulocyte colony-stimulating factor was not given initially but was allowed if grade 4 neutropenia developed. Neutropenia was the major toxicity observed (41% of patients; 16% of courses) and was dose related. However, febrile neutropenia was uncommon (4%), and no patient receiving growth factor developed subsequent grade 4 neutropenia. Only one patient developed grade 4 thromboc...
Cancer, 2002
BACKGROUND. This Phase II multicenter, open-label, single-arm study evaluated the efficacy and safety of a three-drug combination of irinotecan (CPT-11), paclitaxel, and carboplatin in advanced nonsmall cell lung carcinoma (NSCLC). METHODS. Patients received repeated 21-day cycles at starting doses of paclitaxel 175 mg/m 2 administered over 3 hours, followed by carboplatin AUC of 5 over 30 minutes and CPT-11 at a starting dose level of 100 mg/m 2 over 90 minutes, all given on the first day of each cycle. Patients were evaluated for objective tumor response, time to tumor progression (TTP), survival, and safety. RESULTS. Forty patients were enrolled. Baseline patient characteristics included: median age 58 years (range, 32-79); 23 males and 17 females; performance status of 0 (21 patients), 1 (18 patients), or 2 (1 patient); and Stage IIIB (10 patients) and Stage IV (30 patients) disease. A median of six cycles (range, one to eight) were administered. Grade 3-4 toxicities observed in Ն 10% of the patients included neutropenia (78%), asthenia (20%), diarrhea (20%), nausea (18%), vomiting (13%), anemia (10%), and dyspnea (10%). Febrile neutropenia occurred in eight patients (20%), with one death due to neutropenic sepsis. Twelve of 38 evaluable patients had confirmed tumor responses (32%), while 21 (55%) had stable disease (including 12 patients [32%] with minor responses). Only 13% had disease progression at their initial tumor assessment. The median TTP and survival were 5.3 months (range, 0.03-6.2 months) and 12.5 months (range 0.3-28.6ϩ months), respectively. The one and two year survival probabilities were 0.50 (95% confidence interval [CI], 0.28-0.73) and 0.21 (95% CI, 0.0-0.67), respectively. CONCLUSIONS. The combination of CPT-11, paclitaxel, and carboplatin can be safely administered and is active in the treatment of advanced NSCLC. Based on the favorable survival outcome, this regimen is undergoing evaluation in prospective randomized trials.