Phase II study of docetaxel and capecitabine in patients with metastatic or recurrent gastric cancer

OBJECTIVES: A phase II study was conducted to evaluate the response rate and safety of a combination regimen of docetaxel plus capecitabine in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic or recurrent measurable gastric cancer received i.v. docetaxel 75 mg/m2 on day 1 and oral capecitabine 1,000 mg/m2 twice daily from day 1 to 14 every 3-week cycle. RESULTS: Thirty-two patients were enrolled in the current study. Of these, 30 patients were assessable for efficacy and 31 assessable for toxicity. One complete response and 13 partial responses were confirmed, giving an overall response rate of 43.8% (95% CI; 25.6-61.9%). The median time to progression and median overall survival for all patients was 5.07 months and 8.4 months, respectively. Grade 3/4 neutropenia occurred in 3 patients (9.7%) and febrile neutropenia was observed in 2 patients (6.3%). Grade 1/2 nausea was observed in 45.2% of patients. Grade 2-3 hand-foot syndrome occurred in 4 patients (12.9%). CONCLUSIONS: The combination of docetaxel and capectabine was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important first-line treatment option for advanced gastric cancer.     

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.     

A phase II study of oxaliplatin with low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients with advanced gastric cancer

To determine the activity and toxicities of a low dose leucovorin (ldLV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin administered fortnightly (modified FOLFOX-4), as a first-line therapy for patients with advanced gastric cancer. Patients were treated with cycles of oxaliplatin 85 mg/m² on day 1 plus LV 20 mg/m², followed by 5-FU a 400 mg/m² bolus and a 22 hour continuous infusion of 600 mg/m² 5-FU on days 1 - 2 every two week intervals. Forty-five patients were enrolled in this study. Forty-two patients were assessable for response. One of the 42 patients demonstrated complete response, and 20 partial responses, and overall response rate of 50%. The median time to progression and overall survival time were 7.7 months (95% CI: 3.6 - 11.9 months) and 11.2 months (95% CI: 9.1 - 13.3 months), respectively. Major hematologic toxicities included grade 1 - 2 anemia (39.7%), neutropenia (30.4%) and grade 3 - 4 neutropenia (10.9%). Twelve cycles were associated with neutropenic fever. The most common non-hematological toxicities were grade 2 nausea/vomiting (20%). There was no treatment related death. The modified FOLFOX-4 regimen was found to be a safe and effective first line therapy in advanced gastric cancer.     

Multicenter phase II trial of S-1, paclitaxel and cisplatin triplet combination chemotherapy in patients with advanced gastric cancer

Objective

The present study was conducted to evaluate the efficacy and safety of a combination regimen of S-1, paclitaxel plus cisplatin in patients with advanced gastric cancer.

Methods

Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 80?mg/m² plus cisplatin 30?mg/m² on days 1, 8 and S-1 35?mg/m² orally twice daily on days 1?C14 based on a 3-week cycle.

Results

Forty-four patients were enrolled in the current study, among whom 38 were assessable for efficacy and all assessable for toxicity. Two complete response and 24 partial responses were confirmed, giving an overall response rate of 59.1%. At a median follow-up of 11.4?months, the median time to progression and median overall survival was 9.4 (95% CI 6.8?C12.1) months and 11.2 (95% CI 7.6?C14.8) months, respectively. Grade 3/4 neutropenia occurred in 45 events (20.9%) and febrile neutropenia was observed in five events (2.3%). The common non-hematologic toxicity was nausea (grade 1/2, 27.2%) and diarrhea (grade 1/2, 9.0%).

Conclusion

The combination of S-1, paclitaxel and cisplatin was found to be well tolerated and effective in patients with advanced gastric cancer.     

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.     

A phase I/II trial of docetaxel and oxaliplatin in patients with advanced gastric cancer

Purpose  We designed this phase I/II study of docetaxel–oxaliplatin combination chemotherapy to determine the dose-limiting toxicity (DLT), maximum tolerated dose and efficacy as a first-line treatment in patients with advanced gastric cancer. Methods  Patients with histologically proven, chemo-naive gastric adenocarcinoma were eligible. For the phase I part, three dose levels of oxaliplatin and docetaxel every 3 weeks were tested in a cohort of three patients for each level (respectively, 100 and 60 mg/m², 100 and 75 mg/m², 130 and 75 mg/m²). Patients were treated up to a maximum of nine cycles of oxaliplatin and docetaxel unless there was documented disease progression, an unacceptable adverse event, or withdrawal of consent. Results  No DLT was observed at any of the three levels tested in the phase I portion. Therefore, oxaliplatin 130 mg/m² and docetaxel 75 mg/m² were recommended for the phase II study. All 47 patients were evaluable for toxicity and treatment response. The overall response rate was 55.3% (95% CI, 40.6–70.1%) and median duration of response was 4.2 months (range 0.9–9.5 months). After a median follow-up duration of 13.3 months, median overall survival was 12.7 months (95% CI: 10.4–14.9). The median time to progression was 5.0 months (95% CI, 3.4–6.5 months). The main toxicities (grade 3 or 4) were febrile neutropenia (14.9%), neutropenia (23.4%), diarrhea (10.6%) and neurotoxicity (8.5%). Conclusion  The combination of docetaxel and oxaliplatin was feasible with favorable toxicity profile and showed a promising anti-tumor activity in unresectable, metastatic gastric cancer patients.     

多西他赛联合奥沙利铂治疗晚期胃癌的临床观察

目的：观察多西他赛、奥沙利铂联合方案治疗晚期胃癌的疗效和安全性。方法：经病理证实的晚期胃癌患者26例,采用多西他赛联合奥沙利铂,治疗2-4个周期。按照RECIST标准和WHO毒性反应分级标准,分别评价疗效和毒性。结果：26例晚期胃癌患者中,获得CR 0例,PR 8例,SD 12例,PD 6例,总有效率30.8%,疾病控制率76.9%;中位TTP 6.3个月,中位总生存10.7个月,毒性反应主要为血液学毒性、消化道反应和神经毒性等。结论：多西他赛、奥沙利铂联合方案治疗晚期胃癌的客观疗效高,安全性好。     

Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer

5-Fluorouracil-based combination chemotherapy is commonly used in patients with advanced gastric cancer, but results with such therapy are fairly modest. Evaluation of newer agents is therefore required in this disease. Paclitaxel has shown promising activity as a single agent in gastric cancer. In vitro, paclitaxel exhibits sequence-dependent synergy with platinum compounds against gastric cancer. This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with advanced gastric cancer. Twenty-seven patients with measurable or evaluable advanced gastric cancer were enrolled on the study from April 1996 to July 2000. Patients were treated with paclitaxel 200 mg/m intravenously during 3 hours followed by carboplatin at projected area under the curve 5 mg x h x ml (as per the Calvert formula). Twenty-six patients were assessable for toxicity, and 25 patients were assessable for objective response. Nine of the 27 enrolled patients had a major response for an objective response rate of 33% (95% CI 0.17-0.54) by intention-to-treat analysis. The median response duration was 4.9 months (95% CI 2.8-7.3), and median survival was 7.5 months. The 1-year survival rate was 23%. One hundred seventeen courses were administered with a median of four courses per patient administered. The major toxicity was neutropenia, with grade III to IV neutropenia observed in 9 patients (33%) and neutropenic fever in only 1 patient. Grade III peripheral neuropathy developed in two patients, and grade III myalgia and grade III fatigue developed in one patient each. There were no treatment-related deaths. The combination of carboplatin and paclitaxel is a highly tolerable, regimen with activity comparable to that of other regimens in advanced gastric cancer. This regimen needs to be further evaluated in combination with other agents and as a component of multimodality therapy in gastric cancer.     

Phase I/II study of docetaxel and S-1 in patients with advanced gastric cancer

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.     

卡培他滨联合奥沙利铂治疗进展期胃癌68例

目的：观察卡培他滨联合奥沙利铂治疗进展期胃癌的疗效及安全性。方法：经病理证实的进展期胃癌患者,应用卡培他滨2000mg／m^2,分早晚2次口服,d1-d14,服用2周后休息1周;奥沙利铂130mg／m^2,静脉滴注,持续4h以上,d1,21天为1个周期。结果：全组68例患者,获CR2例,PR34例,总有效率为52．9％,中位疾病进展时间（TTP）为7．3个月。中位生存期（OS）11．9个月。1年生存率为42．9％。毒副反应以Ⅰ～Ⅱ度为主,出现Ⅲ度白细胞减少3例、血小板减少5例、恶心呕吐1例以及腹泻4例,无Ⅳ度毒副反应。结论：卡培他滨联合奥沙利铂治疗进展期胃癌有效率较高,毒副反应较低,患者耐受性好。     

A phase II study of docetaxel and oxaliplatin combination in recurrent gastric cancer patients after fluoropyrimidine and/or cisplatin adjuvant treatment: a Korean Cancer Study Group Protocol ST06-02

Background

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.

Methods

Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35?mg/m²) intravenously on day 1 and 8 plus oxaliplatin (100?mg/m²) intravenously on day 1 every 3?weeks until disease progression or unacceptable toxicity.

Results

A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6?months (range, 1–48?months) were enrolled in this trial; 22 (64.7?%) patients had been exposed to both agents. Their median age was 58?years (range, 50–68?years). The overall response rate was 55.9?% (95?% confidence interval (CI), 38.3–73.5?%), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5?months (range, 9.2–50.7?months), the median progression-free survival for all patients was 5.3?months (95?% CI, 4.4–6.1?months) and the median overall survival was 13.8?months (95?% CI, 11.1–16.4?months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1?%) and diarrhea (17.6?%), respectively. Five patients (14.7?%) experienced febrile neutropenia.

Conclusions

Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.     

A Modified Epirubicin and Oxaliplatin Plus Capecitabine (EOX) Regimen as a Second- Line Therapy in Patients with Advanced Gastric Cancer

Objective: We aimed to evaluate the effectiveness of an mEOX (modified epirubicin, oxaliplatin plus capecitabine) regimen as second line therapy after failure of mDCF (modified docetaxel, cisplatin plus fluorouracil). Methods: Gastic cancer patients for whom first-line therapy was unsuccessful and who subsequently received mEOX (epirubicin 50 mg/ m2 on day 1, oxaliplatin 85 mg/m² day 1 and capecitabine twice-daily dose of 625 mg/ m2, p.o. for 2 weeks) every 3 weeks until disease progression or unacceptable toxicity, were retrospectively analyzed. Results: The study population comprised 129 cases with a median age of 55 years (range= 27-78), the majority being male (76 %). Most (75.2%) had ≥ 2 sites of metastasis. The median number of chemotherapy courses was five (range= 2–9). Forty-nine achieved a partial response and 33 showed stable disease, resulting in a ORR (overall response rate) of 38% and a DCR (disease control rate) of 63.6%. The most frequent features of grade 3-4 hematological and non-hematological toxicity were neutropenia (8.5%) and nausea/vomiting (5.4%). None of the patients suffered death due to toxicity. The median PFS was 4.7 months (95% CI, 4.1–5.3) and the OS was 7.4 months (95% CI, 6.3–8.5). On multivariate analysis, age ≥ 60 years and ECOG performance status (0-1) were independent prognostic factors affecting PFS and OS. Conslusions: In advanced gastric cancer patients, who progress after first line chemotherapy and have an ECOG performance status of 0-1, mEOX is a well tolerated triple regimen associated with a promising OS and PFS.     

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.     

Phase II study of capecitabine and irinotecan combination chemotherapy in patients with advanced gastric cancer

The present study was conducted to evaluate the efficacy and safety of a combination regimen of capecitabine plus irinotecan in patients with advanced gastric cancer. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received oral capecitabine 1000 mg m(-2) twice daily from day 1 to 14 and intravenous irinotecan 100 mg m(-2) on days 1 and 8, based on a 3-week cycle. Forty-one patients were enrolled in the current study, among whom 38 were assessable for efficacy and 40 assessable for toxicity. Three complete responses and 16 partial responses were confirmed, giving an overall response rate of 46.3%. At a median follow-up of 269 days, the median time to progression and overall survival were 5.1 and 8.6 months, respectively. Grade 3/4 neutropenia occurred in four patients and grade 3 febrile neutropenia was observed in two patients. Grade 3 diarrhoea and grade 2 hand-foot syndrome occurred in six patients and eight patients, respectively. The combination of capecitabine and irinotecan was found to be well tolerated and effective in patients with advanced gastric cancer. Accordingly, this regimen can be regarded as one of first-line treatment options for advanced gastric cancer.     

Weekly docetaxel and gemcitabine as first-line treatment for metastatic breast cancer: results of a multicenter phase II study

OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.     

Phase II study of weekly docetaxel in patients with metastatic breast cancer.

BACKGROUND: This study was conducted to investigate the efficacy and toxicity of weekly docetaxel administration in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-seven women were treated with 1 h infusions of docetaxel at 40 mg/m2/week after pre-medication with 8 mg dexamethazone. Each cycle consisted of three consecutive weekly treatments followed by a 1 week rest. All patients were assessed for toxicity; five patients were not assessable for clinical response, time to progression (TTP) and overall survival (OS) because of early treatment failure, but they were included in intention-to-treat analysis. RESULTS: Patients received a median of four cycles (range, 1-9), with a median dose intensity of 28 mg/m2/week (range 22-30) and a median relative dose intensity of 0.95 (range 0.73-1.0). No patients showed complete response, whereas 14 had partial response, which accounted for 38% of objective response rate [95% confidence interval (CI) 22% to 53%]. In addition, three patients (8%, 95% CI 0% to 17%) had stable disease over 6 months. Clinical responses were achieved at a median of three cycles (range 1-4 cycles). The median TTP and OS were 5 and 12 months, respectively. The weekly docetaxel regimen was generally well tolerated. About half of the patients experienced grade > or = 1 neutropenia; only 19% had grade 3/4 neutropenia, including one case of grade 4. No febrile neutropenia was observed and fluid retention syndrome was uncommon. Non-hematologic toxicity, however, such as asthenia/fatigue, nail damage, tearing or hearing disorders, was seen with successive treatment cycles. CONCLUSIONS: Weekly docetaxel at 40 mg/m2/week is an active and feasible regimen for patients with metastatic breast cancer.     

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.     

Biweekly docetaxel and vinorelbine in anthracycline-resistant metastatic breast cancer: a multicenter phase II study

The aim of this study was to determine the efficacy and toxicity of a biweekly combination of docetaxel and vinorelbine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines. Eligible patients (n = 49) with MBC received vinorelbine, 25 mg/m2, followed by docetaxel, 60 mg/m2. Cycles were repeated every 14 days for a total of 8 planned cycles. Response rate was evaluated every 4 cycles. All 49 patients were evaluable for safety and 44 for efficacy. Vinorelbine plus docetaxel resulted in an overall response rate of 45% (CI 95%: 31-60) with 2 (4%) complete responses and 18 (41%) partial responses. Patients with visceral metastasis achieved a lower response rate than those without (33% versus 60%, p = 0.044). Time to progression was 11.0 months (CI 95%: 8.6-13.5), and median overall survival was 12.7 months (CI 95%: 9.0-16.4). The most common grade III to IV hematologic adverse events was neutropenia (65% of patients). Febrile neutropenia was observed in 9 cycles (3%) and in 7 patients (14%). Grade III to IV nonhematologic toxicity was rare. Biweekly combination of docetaxel and vinorelbine is an effective and well-tolerated regimen in anthracycline-resistant MBC.     

Phase II study of docetaxel and irinotecan combination chemotherapy in metastatic gastric carcinoma

The current treatment for metastatic gastric cancer (MGC) consists of cisplatin and/or fluorouracil (5-FU) based combination chemotherapy, but cisplatin-based regimens are associated with considerable toxicity. We evaluated the efficacy and safety of a noncisplatin-, non-5-FU-containing regimen, docetaxel/irinotecan in MGC. Chemo-naive patients with MGC received docetaxel (30 mg m(-2)) and irinotecan (70 mg m(-2)) on days 1 and 8 every 3 weeks. The 48 eligible patients (median age 56 years) received a median of four cycles of docetaxel/irinotecan (range 1-18). Of the 46 patients in whom efficacy could be evaluated, 21 showed a partial response (response rate=45.7%; 95% confidence interval (CI) 31.3-60.1%). At a median follow-up of 15.0 months, the median time to progression was 4.5 months (95% CI 3.8-5.2 months) and overall survival was 8.2 months (95% CI, 5.8-10.6 months). Grade 3/4 neutropenia developed in 57.4% of patients, and febrile neutropenia/neutropenic infection in 19.1%. Nonhaematological toxicities were moderate; grade 3/4 diarrhoea occurred in 19.1% of patients, however, was manageable by a dose reduction. There was one possible treatment-related death. In conclusion, weekly docetaxel/irinotecan is a promising outpatient regimen in MGC, with appropriate dose modification.     

Phase II study of weekly oxaliplatin plus infusional fluorouracil and folinic acid (FUFOX regimen) as first-line treatment in metastatic gastric cancer

Oxaliplatin plus fluorouracil/folinic acid (5-FU/FA) every 2 weeks has shown promising activity in advanced gastric cancer. This study assessed the efficacy and safety of weekly oxaliplatin plus 5-FU/FA (FUFOX regimen) in the metastatic setting. Patients with previously untreated metastatic gastric cancer received oxaliplatin (50 mg m(-2)) plus FA (500 mg m(-2), 2-h infusion) followed by 5-FU (2000 mg m(-2), 24-h infusion) given on days 1, 8, 15 and 22 of a 5-week cycle. The primary end point of this multicentre phase II study was the response rate according to RECIST criteria. A total of 48 patients were enrolled. Median age was 62 years and all patients had metastatic disease, with a median number of three involved organs. The most common treatment-related grade 3/4 adverse events were diarrhoea (17%), deep vein thrombosis (15%), neutropenia (8%), nausea (6%), febrile neutropenia (4%), fatigue (4%), anaemia (4%), tumour bleeding (4%), emesis (2%), cardiac ischaemia (2%) and pneumonia (2%). Grade 1/2 sensory neuropathy occurred in 67% of patients but there were no episodes of grade 3 neuropathy. Intent-to-treat analysis showed a response rate of 54% (95% CI, 39-69%), including two complete responses. At a median follow-up of 18.1 months (range 11.2-26.2 months), median survival is 11.4 months (95% CI, 8.0-14.9 months) and the median time to progression is 6.5 months (95% CI, 3.9-9.2 months). The weekly FUFOX regimen is well tolerated and shows notable activity as first-line treatment in metastatic gastric cancer.