Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer.

OBJECTIVE: The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC. PATIENTS AND METHODS: Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m(2) on day 1, every 2weeks plus capecitabine 1000mg/m(2) (or capecitabine 750mg/m(2) if creatinine clearance was 30-50mL/min) twice daily on days 1-7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles. RESULTS: Thirty-five patients were enrolled. Median age was 78years (range, 70-83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5-11.7) and 15.5 (95% CI: 9.6-21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1-2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death. CONCLUSION: Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC.

Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.

BACKGROUND: Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS: After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS: Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS: Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

Biweekly administration of docetaxel and vinorelbine as second-line chemotherapy for patients with stage IIIB and IV non-small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP 013-02).

The current report aims to evaluate the efficacy and safety profile of a biweekly administration of docetaxel and vinorelbine to patients with advanced non-small cell lung cancer, who had previously been treated for this disease. In a prospective, multicenter, open-label, phase II trial, patients received 40 mg/m of docetaxel and 20 mg/m of vinorelbine on days 1 and 15, every 28 days. Treatment continued for up to a maximum of six cycles, unless disease progression or unacceptable toxicity occurred, or consent was withdrawn. Fifty patients were enrolled in the study and they received 174 cycles of chemotherapy, with a median of three cycles per patient. All patients were evaluated for efficacy and toxicity in an intention-to-treat analysis. The overall response rate was 10% [95% confidence interval (CI): 1-19], including one complete response (2%) and four partial responses (8%). Previous chemotherapy of 80% of the responders included paclitaxel. Median time to disease progression was 2.7 months (95% CI: 2.2-4.3) and median overall survival was 6.5 months (95% CI: 2.5-9.2). The survival rates at 1 and 2 years were 18% (95% CI: 7-29) and 4% (95% CI: 0-10), respectively. The most frequent severe toxicities were neutropenia (20% of patients) and leukopenia (8% of patients). Other toxicities appeared in 4% or fewer of the patients. Biweekly administration of docetaxel and vinorelbine is feasible as a second-line treatment for non-small cell lung cancer patients, but its level of activity and toxicity does not suggest any advantage compared with the results obtained with single-agent docetaxel in the same setting.

Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial.

BACKGROUND: We aimed to compare the additional benefit of gemcitabine when combined with vinorelbine above that of standard vinorelbine treatment in patients with metastatic breast cancer. METHODS: In this phase III, multicentre, open-label, randomised study, 252 women with locally recurrent and metastatic breast cancer who had been pretreated with anthracyclines and taxanes were randomly assigned single-agent vinorelbine (30 mg/m(2), days 1 and 8) or gemcitabine plus vinorelbine (1200/30 mg/m(2), days 1 and 8). Both study treatments were administered intravenously every 21 days until disease progression, unacceptable toxic effects, or stoppage at the request of investigator or patient. The primary endpoint was median progression-free survival. Secondary objectives included assessments of response rate, disease duration, overall survival, and characterisation of the toxicity profiles of both regimens. This study is registered with ClinicalTrials.gov, number NCT00128310. FINDINGS: Between 2001 and 2005, 252 women were recruited and randomised for treatment. One of these patients was ineligible. Prognostic factors were well balanced between treatment groups (median number of metastatic sites in combination group 2 (range 0-5) and in vinorelbine group 2 (range 1-6); visceral disease in 76% and 75% of patients, respectively). Median progression-free survival was 6.0 months (95% CI 4.8-7.1) for patients given gemcitabine plus vinorelbine and 4.0 months (2.9-5.1) for those assigned vinorelbine; there was 1.9 months of difference (hazard ratio 0.66 [0.50-0.88]; p=0.0028). Overall survival was 15.9 months (12.6-19.1) for the gemcitabine plus vinorelbine group and 16.4 months (11.6-21.0) for the vinorelbine group; there was 0.5 months of difference (hazard ratio 1.04 [0.78-1.39]; p=0.8046). Objective response rates were 36% for patients assigned gemcitabine plus vinorelbine (n=45) and 26% for those assigned vinorelbine (n=33) (p=0.093). Grade 3 or 4 neutropenia was reported in 75 (61% [52-70]) of the participants assigned gemcitabine plus vinorelbine, compared with 55 (44% [35-53]) of those assigned vinorelbine alone (p=0.0074). Febrile neutropenia occurred in 13 (11%) of those assigned gemcitabine plus vinorelbine, and in seven (6%) of those assigned vinorelbine alone (p=0.15). Incidences of grade 3 or 4 non-haematological toxic effects were similar between the two treatment groups. INTERPRETATION: Patients with metastatic breast cancer assigned gemcitabine and vinorelbine had better progression-free survival compared with those assigned vinorelbine alone. However, this finding did not translate into a difference in overall survival. Although toxicity was manageable, patients in the combined group had more haematological toxic effects. These factors should be taken into account when deciding which chemotherapy patients should receive.

Gemcitabine plus docetaxel as first-line chemotherapy in patients with advanced non-small cell lung cancer: a lung cancer Galician group phase II study.

BACKGROUND: Numerous phase II and III clinical trials have demonstrated a higher activity of combined gemcitabine plus docetaxel schedules against non-small cell lung cancer (NSCLC) than that of both agents in monotherapy. METHODS: This phase II study evaluated a 3-week based schedule of docetaxel 85 mg/m(2) (1-h i.v. infusion, d8) combined with gemcitabine 1,000 mg/m(2) (30-min i.v. infusion; d1,8) as first-line chemotherapy for patients with advanced NSCLC. RESULTS: Forty-one patients with non-resectable, stage IIIB/IV, and bidimensionally measurable disease were enrolled. A total of 182 chemotherapy cycles (median 6, range 1-6) was administered to 40 patients during the study; one patient did not receive chemotherapy due to a protocol deviation. Two patients were not evaluable for treatment efficacy. The overall response rate found was 44% (95% CI, 29-59%): three patients (7%) had a complete response and 15 patients (37%) had a partial response (median duration of response = 4.0 months). With a median follow-up of 8.7 months, the median time to disease progression was 4.4 months and the median overall survival was 7.3 months. The combined gemcitabine plus docetaxel chemotherapy was well tolerated except for pulmonary toxicity. The main grade 3-4 hematological toxicity was neutropenia (28% of patients, 9% of cycles). Two cases of febrile neutropenia were reported. The main grade 3-4 non-hematological toxicity was pulmonary toxicity (23% of patients, 6% of cycles). CONCLUSION: Gemcitabine 1,000 mg/m(2) on days 1 and 8 in combination with docetaxel 85 mg/m(2) on day 8 given in 3-week cycles is an active and well-tolerated first-line chemotherapeutic regimen for advanced NSCLC.

Biweekly docetaxel as second-line chemotherapy of patients with advanced non-small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP 006-00).

This phase II trial assessed the antitumoral activity and toxicity of docetaxel 50 mg/m (1-h i.v. infusion) administered every 2 weeks as second-line treatment in 45 patients with advanced non-small cell lung cancer (NSCLC). A total of 251 infusions (median 4 per patient) were administered. The actual and relative median dose intensity values were 24.2 mg/m/week and 0.97, respectively. Thirty-seven patients were evaluable for tumor response. The overall response rate was 20% [95% confidence interval (CI) 8-32%] and included one complete response (2%) and eight partial responses (18%). Stable disease was found in seven patients (16%). With a median follow-up of 4 months, the median time to disease progression was 2.8 months (95% CI 1.9-3.7), the median overall survival was 4.0 months (95% CI 3.4-4.6) and the 1-year survival rate was 23% (95% CI 9-37). The every-2-weeks docetaxel schedule was well tolerated. Grade 3/4 non-hematological toxicities showed rates of 5% or less of patients and 2% or less of cycles. The main grade 3/4 hematological toxicity was neutropenia (16% of patients and 8% of cycles). No febrile neutropenia was found. Nevertheless, one toxic death was reported. We conclude that the biweekly docetaxel schedule showed an antitumoral activity similar to that found with the every-3-weeks or weekly docetaxel schedule in a second-line setting for advanced NSCLC. This antitumoral effect was associated with a marked reduction in hematological toxicity, therefore suggesting that this new docetaxel schedule might be useful in the design of combined second-line schedules for treating NSCLC.

Phase II trial of vinorelbine and estramustine in the treatment of metastatic hormone-resistant prostate cancer.

The purpose of this study was to investigate the efficacy and safety of combination chemotherapy using estramustine and vinorelbine in chemotherapy-naïve patients with hormone-resistant prostate cancer (HRPC). The patients (n = 54) received oral estramustine 840 mg/day on Days 1 to 14 and IV vinorelbine 25 mg/m(2) on Days 1 and 8 of every 3 wk cycle. The median number of cycles per patient was 9 (range, 1 to 27). Fifty-three patients were evaluable for toxicity and survival and 52 for prostate specific antigen (PSA) response. Median age was 68 (range, 46-80). PSA sustained decrease >50% was seen in 52% of patients (95% CI: 38-66%). A complete response was seen in 3 and a partial response in 12 of 25 patients with measurable disease, for an overall objective response of 60% (95% CI: 41-79%). Improvement in performance status was observed in 30 out of 43 evaluable for clinical benefit response. The median duration of response was 7 mo and median time to progression was 6 mo. The median survival time was 15 mo. The most common adverse event was mild gastrointestinal toxicity. In general, toxicity G3-4 was low: granulocytopenia Grade 3-4 (8%), thrombocytopenia Grade 3 (6%), and anemia Grade 3 (13%). Other Grade 3 toxicities included deep vein thrombosis (4%), hepatic (2%), cardiac ischemia (2%), fatigue (6%), and sensory neuropathy (2%). There were 2 treatment-related deaths (4%). We conclude that vinorelbine and estramustine as used in this trial is an efficacious and well-tolerated therapeutic regimen in the management of HRPC.