Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial

Capecitabine and docetaxel have single-agent activity in upper gastrointestinal tumours, and have together demonstrated preclinical synergy and a survival benefit in breast cancer, and high response rates in first-line metastatic gastric cancer. This trial assessed the efficacy, safety and feasibility of capecitabine in combination with docetaxel in patients with metastatic oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m(-2) twice daily on days 1-14) plus intravenous docetaxel (75 mg m(-2) on day 1) every 3 weeks as first- (n = 16) or second-line (n = 8) therapy. Patients received a median of four cycles of treatment (range, 0-6). The median follow-up is 16.5 months (range, 7.9-21.4 months). Intent-to-treat efficacy analysis showed an overall response rate of 46%. Of the 11 responders (one complete and 10 partial), nine of 16 (56%) received first-line and two of eight (25%) received second-line therapy. The median time to progression was 6.1 months (95% confidence interval (CI), 4.5-7.7 months). The median survival was 15.8 months (95% CI, 7.8-23.9 months). Severe adverse events (grade 3/4) reported were: neutropenia (42%, including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%), sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus docetaxel has a manageable adverse event profile and very promising activity in metastatic oesophageal cancer, at least comparable to other doublet regimens. Therefore, the combination merits further investigation in this setting.     

First- and second-line chemotherapy with docetaxel or mitoxantrone in patients with hormone-refractory prostate cancer: does sequence matter?

BACKGROUND: Docetaxel and mitoxantrone are considered first-line chemotherapeutic options in patients with hormone-refractory prostate cancer (HRPC), but their clinical effectiveness in a second-line setting is unknown. Therefore, the authors conducted a population-based retrospective study to establish activity and tolerability of second-line docetaxel or mitoxantrone in HRPC. METHODS: The study included 68 patients who had failed androgen ablation therapy and who received docetaxel and mitoxantrone in either sequence. Clinical efficacy in terms of median overall survival (OS), progression-free survival (PFS), posttreatment prostate-specific antigen (PSA) decline of > or = 50% and treatment-related toxicity were evaluated. RESULTS: Of 68 patients, 35 received docetaxel followed by mitoxantrone, and 33 received mitoxantrone followed by docetaxel. Both groups were comparable for recognized pretreatment prognostic factors. Patients who received docetaxel first-line had a trend toward longer median OS compared with patients treated with second-line docetaxel after mitoxantrone failure (22 mos, 95% confidence interval [CI], 17.2-26.8 mos vs. 15 mos, 95% CI, 10.4-19.6 mos). Median number of second-line chemotherapy cycles was 3 and median PFS survival was 2-3 months in both groups. Second-line docetaxel produced a higher PSA response compared with mitoxantrone (38% vs. 12%, P = 0.012), but this did not translate to a survival benefit. Both second-line docetaxel and mitoxantrone were associated with a high frequency of treatment-related adverse events that resulted in dose reduction, delay, or discontinuation (64% and 46% of patients, respectively). CONCLUSIONS: Study results favored docetaxel given up-front for patients with HRPC considered suitable for further chemotherapy. Second-line docetaxel or mitoxantrone had limited efficacy and tolerability. Patients who are candidates for second-line chemotherapy, should be enrolled into clinical trials.     

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.     

多西他赛联合卡培他滨二线治疗晚期食管鳞状细胞癌的Ⅱ期研究

目的 研究多西他赛联合卡培他滨二线治疗晚期食管鳞状细胞癌的疗效、患者不良反应、至疾病进展时间（TTP）和总生存（OS）.方法 30例一线治疗失败的晚期食管鳞状细胞癌患者接受多西他赛60 mg/m2,第1天,静脉滴注1h;卡培他滨每天825 mg/m2,分2次口服,第1天至第14天;21d为1个周期,最多不超过6个周期.结果 30例患者接受中位2个周期（2～6个周期）化疗.中位随访时间15.4个月（3.0 ～ 31.5个月）.疗效评价为部分缓解7例（23.3％）,稳定13例（43.3％）.中位TTP为3.0个月（95％CI 1.929 ～ 4.071）,中位OS为8.3个月（95％CI 6.848 ～ 9.752）.严重（3/4级）不良反应为中性粒细胞减少10例,贫血5例,血小板减少3例,手足综合征4例和疲乏3例.结论 多西他赛联合卡培他滨对一线治疗失败的晚期食管鳞状细胞癌患者有效,不良反应可接受,可考虑作为治疗晚期食管鳞状细胞癌的二线化疗方案.     

Second-line,low-dose,weekly paclitaxel in patients with stage IIIB/IV nonsmall cell lung carcinoma who fail first-line chemotherapy with carboplatin plus paclitaxel

BACKGROUND: Second-line chemotherapy with docetaxel improves survival and quality of life (QoL) in patients with nonsmall cell lung carcinoma (NSCLC) who fail first-line platinum-based regimens. The authors sought to determine the activity of second-line, low-dose, weekly paclitaxel in patients with NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. METHODS: Patients with Stage IIIB/IV NSCLC who had received first-line carboplatin/paclitaxel were treated with low-dose (80 mg/m(2)), weekly paclitaxel at the time of disease progression. Response rates, QoL, and survival were outcome end points. RESULTS: Sixty-two patients were included in this analysis. The median age was 62 years (range, 32-76 years), 55% of patients were male, 89% of patients had Stage IV NSCLC, and the Karnofsky performance status was 90-100% in 31% of patients, 70-80% in 55% of patients, and 60% in 14% of patients. Twenty-six percent of patients experienced disease progression as their best response to first-line carboplatin plus paclitaxel, whereas 52% of patients had stable disease, and 23% of patients had achieved a response. The median time from first-line carboplatin plus paclitaxel to second-line, low-dose, weekly paclitaxel was 9.5 weeks (range, 1-78 weeks). The toxicity profile was extremely favorable, with no Grade 4 toxicity and < 10% Grade 3 hematologic or nonhematologic toxicity in all patients with the exception of neuropathy. Ten percent of patients experienced both Grade 2 and Grade 3 neuropathy. The overall objective response rate was 8%. The median survival was 5.2 months (95% confidence interval [95%CI], 3.6-6.2 months), and the 1-year and 2-year survival rates were 20% (95%CI, 10-30%) and 9% (95%CI, 1-16%), respectively. CONCLUSIONS: Second-line, low-dose, weekly paclitaxel had activity in selected patients with Stage IIIB/IV NSCLC who failed first-line chemotherapy with carboplatin plus paclitaxel. The toxicity profile of this approach is extremely favorable, and outcome expectations are similar to the outcome expectations with other single agents in this setting.     

Phase II study of first-line sequential chemotherapy with gemcitabine-carboplatin followed by docetaxel in patients with advanced non-small cell lung cancer

RATIONALE: Despite the use of novel chemotherapeutic agents, patients with advanced non-small cell lung cancer (NSCLC) continue to show a poor survival. OBJECTIVES: To assess the safety and efficacy of a novel sequential and putatively non-cross-resistant chemotherapy regimen. METHODS: Eligibility included: stages IV and IIIB (malignant pleural effusion), performance status 0-1, and adequate renal, hepatic and bone marrow function. Patients with previously treated and controlled brain metastases were not excluded. Responses were determined according to the Response Evaluation Criteria in Solid Tumors. Treatment consisted of gemcitabine, 1,000 mg/m2, on days 1 and 8, and carboplatin, AUC = 5, on day 1 every 4 weeks (2-4 cycles) followed by docetaxel, 75 mg/m2, on day 1 every 3 weeks (4 cycles). Docetaxel was given after four cycles of gemcitabine-carboplatin or if progression of disease occurred, after the first two cycles. RESULTS: Forty patients were enrolled. All patients received at least one cycle of gemcitabine-carboplatin. Due to PD, 15 patients received fewer than four cycles and only 1 received docetaxel subsequently. Of the 25 patients who completed four cycles of gemcitabine-carboplatin, 23 received docetaxel.In total, 24 patients received at least one cycle of docetaxel, and 12 patients completed four cycles of both regimens. The overall response rate was 23.6% (9/38 patients, 95% confidence interval, CI, 11-40%), with 15.8% (6/38 patients, 95% CI, 6-31%) and 12.5% (3/24 patients, 95% CI, 3-32%) response rates to gemcitabine-carboplatin and docetaxel, respectively. No patient with PD on gemcitabine-carboplatin responded to docetaxel. Toxicities were tolerable and mostly hematologic. Median survival time and progression-free survival were 6.7 and 4.9 months, respectively, with a 1-year survival of 37.5%. CONCLUSION: Sequential gemcitabine-carboplatin and docetaxel can be safely administered in advanced NSCLC. Our results are comparable to those achieved with other similar regimens and do not represent a significant improvement in the treatment of advanced NSCLC.     

Docetaxel plus cisplatin as second-line therapy in metastatic or recurrent advanced gastric cancer progressing on 5-fluorouracil-based regimen

The purpose of this study was to determine the activity and safety of docetaxel plus cisplatin as second-line chemotherapy for advanced gastric cancer. This trial included patients who had failed first-line chemotherapy with a 5-fluorouracil regimen within 1 year before their enrollment. After registration, patients were treated with docetaxel intravenously at a dose of 60 mg/m2 given over 1 hour followed by cisplatin 60 mg/m2 given over 2 hours. The treatment was continued every 3 weeks until disease progression or unacceptable toxicity was detected. Forty-three patients were registered and 41 were assessable for response. Seven partial responses were observed (17.1% of the "evaluable" patients; 95% confidence interval [CI], 0-29) with a median response duration of 3.9 months. Stable disease was documented in 2 cases (4.9%). The median survival was 5.8 months (95% CI, 3.4-8.3), resulting in a 1-year survival rate of 23%. Tolerance was acceptable, with the main toxicity being neutropenia. The authors conclude that second-line chemotherapy with docetaxel plus cisplatin for advanced gastric cancer is feasible with an acceptable toxicity level.     

Efficacy and toxicity of gemcitabine plus docetaxel combination as a second line therapy for patients with advanced stage soft tissue sarcoma

Purpose: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. Patients and Methods: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 mg/m2 on days one and eight intravenously over 90 minutes, followed by docetaxel 75 mg/m2 on day eight intravenously over one hour. Cycles were repeated every 3 weeks. Results: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3 %) patients (2 CR, 11 PR) and stable disease in 21 (32.8 %). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1 %). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range;1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9 %). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5 %), mucositis (32.8 %), peripheral neuropathy (29.7%), and fatigue (26 %). There was no toxicity-related death. Conclusion: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.     

Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients.

PURPOSE: To evaluate the safety and efficacy of bevacizumab and weekly docetaxel as first- or second-line therapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Twenty-seven MBC patients received i.v. bevacizumab at 10 mg/kg on days 1 and 15 in combination with i.v. docetaxel 35 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Primary end points were to assess toxicity, overall response rate, and progression-free survival. A secondary end point was to assess the relationship between plasma endothelial and cell adhesion markers and clinical outcomes. RESULTS: One-hundred fifty-eight treatment cycles were administered with a median of six cycles (range 1-15 cycles) per patient. The most common grade 4 toxicities per patient were as follows: 2 (7%)-pulmonary embolus, 1 (4%)-febrile neutropenia, and 1 (4%)-infection; grade 3 toxicities were 4 (15%)-neutropenia, 4 (15%)-fatigue, 2 (7%)-neuropathy, 2 (7%)-athralgias, 2 (7%)-stomatitis, 1 (7%)-pleural effusion, and 1 (4%)-hypertension. The overall response rate was 52% [95% confidence interval (95% CI), 32-71%], median response duration was 6.0 months (95% CI, 4.6-6.5 months), and the median progression-free survival was 7.5 months (95% CI, 6.2-8.3 months). In hypothesis-generating univariate and limited multivariate analyses, E-selectin was statistically significantly associated with response to the combination. CONCLUSION: Bevazicumab in combination with weekly docetaxel is active with acceptable toxicities in MBC. Additional studies evaluating E-selectin as a marker of response to bevacizumab-containing chemotherapy are warranted.     

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.     

Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m(-2) of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1-3, 8-10, 15-17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1-9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44-72) and median duration of PSA response was 8.0 months (95% CI: 6.9-9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel.     

High-dose epirubicin plus docetaxel at standard dose with lenograstim support as first-line therapy in advanced breast cancer

On the basis of preclinical and clinical data, we designed a phase II study to determine the efficacy and feasibility of high-dose epirubicin plus docetaxel (Taxotere) with lenograstim support, as first-line therapy for patients with advanced breast cancer. Patients with histologic evidence of metastatic breast cancer, without previous chemotherapy, adequate organ functions, Eastern Cooperative Oncology Group performance status less than 2, and signed informed consent entered in the trial. Treatment consisted of premedication the day before the treatment day for 3 consecutive days (dexamethasone 16 mg o.r. and 5-HT3 antagonists). On the treatment day 1, epirubicin 130 mg/m2 was administered as a 15-minute intravenous infusion followed 1 hour later by 1-hour intravenous infusion of docetaxel 100 mg/m2. Cycles were repeated every 21 days, for a maximum of 8 cycles. Lenograstim (5 microg/kg, s.c.) was started 48 hours later (day 4) and was given daily for 10 consecutive days. Response evaluation was made after the third cycle was applied, following World Health Organization criteria. Responding patients received five additional cycles. Median time to progression and survival were calculated according to the Kaplan-Meier method. A total of 32 patients have been included in the study. A total of 236 courses were delivered. A total response rate of 87.5% (95% confidence interval [CI] of 77-98) was obtained. There were 11 complete responses and 17 partial responses. Toxicity was mild, with a low incidence of undesirable effects (7 cycles, 2.9% were delayed from 3 to 6 days because of neutropenia). After a median follow-up time of 490 days (range, 131-966 days), the median time to progression was 490 days (95% CI 314-575), and the median survival was 604 days (95% CI 513-785). This epirubicin plus docetaxel regimen is an efficient treatment for patients with advanced breast cancer. The lenograstim support allows the administration of such a chemotherapy regimen with a modest incidence of side effects. A larger number of patients need to be evaluated.     

Docetaxel, capecitabine and carboplatin in metastatic esophagogastric cancer: a phase II study

PURPOSE: A Phase I investigation of docetaxel, carboplatin, and capecitabine at our institution demonstrated the safety and tolerability of this regimen in patients with metastatic esophagogastric cancer. The objectives of this Phase II study were to determine the response rate, toxicity, and survival for patients with metastatic esophagogastric cancer treated with this regimen. MATERIALS AND METHODS: Chemotherapy na?ve patients with metastatic esophageal or gastric cancer received a regimen comprised of docetaxel 40 mg/m(2), days 1 and 8, carboplatin AUC = 2, Days 1 and 8, and capecitabine 2000 mg/m(2), Days 1-10 in 21-Day cycles. Patients were treated until disease progression or unacceptable toxicity. RESULTS: Twenty-five patients were treated with a median of 4 cycles of chemotherapy. Twelve of 25 patients (48 percent) had a Grade 3/4 toxicity. There were no Grade 4 nonhematologic toxicities, and 1 patient (4 percent) had neutropenic fever. There were 3 complete responses, and 9 partial responses, for an overall response rate of 48 percent. The median survival was 8 months (95% confidence interval, 5.5-13 months), and the 1-year survival was 36 percent. CONCLUSIONS: Weekly docetaxel and carboplatin with capecitabine was an easily administered outpatient regimen. The response rate and 1-year survival were similar to more complex regimens. Future trials may investigate the substitution of carboplatin with more active agents.     

Dose escalation study of carboplatin–pemetrexed followed by maintenance pemetrexed for elderly patients with advanced nonsquamous nonsmall-cell lung cancer

BackgroundThis study was designed to determine the recommended dose of carboplatin–pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC).Patients and methodsPatients received escalated doses of carboplatin and pemetrexed every 3 weeks for four cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed.ResultsThe combination of carboplatin at an area under the concentration–time curve (AUC) of 5, and 500 mg/m² pemetrexed, was determined to be the recommended dose for elderly patients with advanced nonsquamous NSCLC. Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance therapy without unexpected or cumulative toxic effects. The study had an overall response rate of 47.1%. The median progression-free survival time was 142 days (95% confidence interval [CI] 68–216 days) and the median overall survival time was 461 days (95% CI 168–754 days).ConclusionsThis combination was a tolerable and effective regimen, and recommended dose (RD) was carboplatin [area under the curve (AUC) of 5]/pemetrexed (500 mg/m²) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced nonsquamous NSCLC.     

Docetaxel plus gemcitabine or docetaxel plus cisplatin in advanced pancreatic carcinoma: randomized phase II study 40984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group.

PURPOSE: To define the efficacy and toxicity of docetaxel plus gemcitabine or docetaxel plus cisplatin for advanced pancreatic carcinoma. PATIENTS AND METHODS: Chemotherapy-naive patients with measurable disease and WHO performance status less than 2 were randomly assigned to receive 21-day cycles of gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8 (arm A) or docetaxel 75 mg/m2 on day 1 plus cisplatin 75 mg/m2 on day 1 (arm B). Primary end points were tumor response and rate of febrile neutropenia grade. RESULTS: Of 96 randomly assigned patients (49 patients in arm A and 47 patients in arm B), 70 patients were analyzed for response (36 in arm A and 34 in arm B) and 89 patients were analyzed for safety (45 in arm A and 44 in arm B). Confirmed responses were observed in 19.4% (95% CI, 8.2% to 36.0%) of patients in arm A and 23.5% (95% CI, 10.7% to 41.2%) in arm B. In arm A, the median progression-free survival (PFS) was 3.9 months (95% CI, 3.0 to 4.7 months), median survival was 7.4 months (95% CI, 5.6 to 11.0 months), and 1-year survival was 30%. In arm B, the median PFS was 2.8 months (95% CI, 2.6 to 4.6 months), median survival was 7.1 months (95% CI, 4.8 to 8.7 months), and 1-year survival was 16%. Febrile neutropenia occurred in 9% and 16% of patients in arms A and B, respectively. CONCLUSION: Both regimens are well tolerated and show activity in advanced pancreatic carcinoma. The safety profile and survival analyses favor docetaxel plus gemcitabine for further evaluation.     

Phase II multicentre study of docetaxel plus 5-fluorouracil in patients with anthracycline-pretreated metastatic breast cancer

The purpose of the study was to determine the efficacy and safety of docetaxel plus continuous infusion of 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracyclines. A total of 41 patients with histologically proven metastatic breast cancer and performance status 0-2, who had received at least one anthracycline-containing regimen, received docetaxel 85 mg m(-2) followed by continuous infusion of 5-FU 750 mg m(-2) day(-1) for 5 days every 3 weeks for up to eight cycles. All patients received corticosteroid premedication, but there was no prophylactic colony-stimulating factor support. The most frequent metastatic sites were the liver (61%), bone (29%), and lung (29%). All 41 patients were assessable for toxicity and 30 were eligible and assessable for efficacy. The objective response rate was 70.0% (95% CI: 53.6-86.4%) for the per protocol group and 53.7% (95% CI: 38.4-68.9%) for the intent-to-treat (ITT) population. For the ITT population, median duration of response was 8.4 months (95% CI: 6.7-12.2 months), median time to progression was 6.7 months (95% CI 5.5-8.6 months), and median survival was 17 months (95% CI: 12.3-not recorded months). Grade 3/4 neutropenia occurred in 54% of patients, with febrile neutropenia in 24% of patients and 5% of cycles, but infections were rare. Stomatitis was frequent, grade 3 in 24% of patients and grade 4 in one patient (2%), but manageable. Diarrhoea was rare, grade 3 in 7% of patients and 1% of cycles. Other grade 3/4 nonhaematological toxicities were infrequent. In conclusion, this docetaxel/5-FU regimen is highly active and well tolerated in patients with anthracycline-pretreated metastatic breast cancer. The efficacy is particularly promising, as one-third of patients were either second-line and/or anthracycline-resistant/refractory.     

Gemcitabine and carboplatin in patients with locally advanced or metastatic non-small cell lung cancer: a prospective phase II study

PURPOSE: The primary objective of this phase II study was to determine the tumor remission rates in previously untreated patients with advanced or metastatic non-small cell lung cancer (stage IIIB and IV), after treatment with gemcitabine plus carboplatin. Secondary objectives of this study were to determine toxicity, median survival and progression free survival in the same patient population treated with gemcitabine plus carboplatin. PATIENTS AND METHODS: Chemonaive patients with histological or cytological diagnosis of stage IIIB or IV NSCLC and Karnofsky performance status >/=60 received gemcitabine 1000 mg/m(2) over 30 min on days 1 and 8 and carboplatin AUC 5.0 over 30 min on day 1 after the gemcitabine infusion. Treatment cycles were repeated every 21 days for a maximum of six cycles, or until disease progression or unacceptable toxicity occurred. RESULTS: Of the 60 patients qualified for efficacy analysis, five achieved complete remissions, 15 partial remissions and 33 had stable disease, for an overall objective response rate (CR+PR) of 33.3% (95% CI, 21.7-46.7%). Four patients had progressive disease. The predominant toxicity was hematologic, with grade 3/4 leucopoenia being most common (35% patients). The median duration of response was 5 months, median time to progression was 6 months and median survival was 9 months with 80% of patients censored. CONCLUSION: Gemcitabine plus carboplatin is an effective and well tolerated treatment for advanced NSCLC.     

A phase II study of days 1 and 8 combination of docetaxel plus gemcitabine for the second-line treatment of patients with advanced non-small-cell lung cancer and good performance status

OBJECTIVE: We conducted a phase II trial to evaluate the efficacy and toxicity of a combination consisting of second-line docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy. PATIENTS AND METHODS: Eligibility criteria: histologically confirmed advanced NSCLC with progressive disease to platinum-based chemotherapy, ECOG performance status (PS) 0 or 1, and adequate kidney, liver and bone marrow function. Treatment consisted of docetaxel 36 mg/m(2) i.v. over 60 min followed by gemcitabine 1000 mg/m(2) i.v. over 30 min on days 1 and 8 of each 3-week cycle for a planned six cycles or unacceptable toxicity. RESULTS: Of the 52 patients enrolled, 50 were evaluable for response and toxicity. The mean age was 59 years (range 42-79), 46 male and 4 female. Histology subtypes were: adenocarcinoma 26 patients, bronchioloalveolar 1 patient, large cell carcinoma 5 patients, and squamous cell carcinoma 18 patients. Thirty-eight patients had ECOG PS 1 and 12 patients had PS 0. The median number of cycles administered was four (range 2-6). The overall response rate was 28%. The median follow-up was 9 months (range 5-34 months). The median survival time (MST) was 8.2 months (95% CI, 4-12%), and the 1-year survival was 25%. The median progression-free survival was 4.4 months (95% CI, 2-6%). In the Cox regression model, survival was only significantly affected by the PS. The median survival in patients with PS 0 was 17.8 months (95% CI, 18.8-21.8%) compared with a median survival for patients with PS 1 of 6.1 months (95% CI, 4.1-8.2%) (P=0.0057). Toxicity: three patients had grade 3 anemia, three patients had grade 3 thrombocytopenia, four patients had grade 3 neutropenia and only one patient developed grade 4 febrile neutropenia. Non-hematologic toxicity was also mild; the most frequent was asthenia, with grade 3 in eight patients (16%), and one patient with grade 4. CONCLUSION: This regimen of docetaxel in combination with gemcitabine in advanced second-line NSCLC is an active and safe regimen.     

Gemcitabine and vinorelbine as first-line chemotherapy for advanced non-small cell lung cancer: a phase II trial

The purpose of this phase II study was to investigate the efficacy and safety of gemcitabine plus vinorelbine as first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Eligibility criteria included cytologically or histologically confirmed NSCLC (stage IIIB or IV), no previous chemotherapy, and bidimensionally measurable disease. Patients received 1000 mg/m(2) gemcitabine and 30 mg/m(2) vinorelbine on days 1, 8 and 15 every 4 weeks up to eight courses. From December 1997 to November 1998, 70 patients (59 stage IV and 11 stage IIIB disease), with a median age of 59 years (range 38-74 years) were enrolled. The intent-to-treat response rate was 41% (95% confidence interval (CI) 30-54%) with 1 complete responder (CR) and 28 partial responders (PRs), 15 patients had stable disease (SD) and 26 progressed (PD). Median survival was 8.3 months (95% CI 6.0-9.9 months), median progression-free survival (PFS) was 4.8 months (95% CI 3.9-5.5 months), and 1-year survival rate was 33.5% (95% CI 24.0-46.8%). Patients received a total of 229 cycles. Haematological and non-haematological toxicities were moderate. Transient World Health Organization (WHO)-grade IV leucopenia and thrombocytopenia occurred in 13 (6%) and two (1%) cycles, respectively. The predominant non-haematological toxicity was local reactions of the veins in 19 (27%) patients (WHO-grade II and III). Neurotoxicity was infrequent, non-cumulative, and reversible. The combination of gemcitabine and vinorelbine has demonstrated activity in metastatic NSCLC, with response and survival rates similar to those of cisplatin-based regimens and a more favourable toxicity profile that is well tolerated in an outpatient setting.     

Second-line chemotherapy with Capecitabine (Xeloda) and Docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial

Purpose

To investigate the efficacy and toxicity of the docetaxel and capecitabine combination in patients with previously treated, unresectable adenocarcinoma of the pancreas.

Patients and Methods

Patients with pancreatic adenocarcinoma, pre-treated with gemcitabine-based chemotherapy, were treated with capecitabine (800?mg/m² orally, twice a day for 14?days) and docetaxel (75?mg/m² i.v, on day1), every 3?weeks. The primary end-point was overall response rate (RR).

Results

Thirty-one patients were enrolled in the study; 93.6% of them had a performance status (PS) of 0?C1 and 96.8% had stage IV disease. Patients received a median of 4 cycles/patient, and the main reason for treatment discontinuation was disease progression. Partial response was observed in three (9.7%) patients, stable disease in seven (22.6%) (disease control rate: 32.3%, 95% CI: 15.80?C48.71%) and disease progression in 21 (67.6%). The median progression-free survival (PFS) was 2.4?months (95% CI: 1.6?C3.13) and the median overall survival (OS) was 6.3?months (95% CI: 3.38?C9.23); the estimated 1-year survival rate was 14.7%. Grade III/IV neutropenia occurred in 10 (32.2%) patients and febrile neutropenia in one patient. Other severe non-hematologic toxicities were mild and manageable. After 2 chemotherapy cycles, pain control occurred in 20% of patients and stabilization of body weight in 40%.

Conclusion

The combination of docetaxel/capecitabine may confer good disease control associated with improvement of quality of life as second-line chemotherapy in patients with metastatic pancreatic cancer.