Docetaxel plus gemcitabine in combination with capecitabine as treatment for inoperable pancreatic cancer: a phase II study.

PURPOSE: To evaluate the activity and tolerance of gemcitabine in combination with docetaxel and capecitabine in previously untreated patients with advanced pancreatic cancer. PATIENTS AND METHODS: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were treated with gemcitabine (1,500 mg/m(2) on days 1 and 15), docetaxel (50 mg/m(2) on days 1 and 15) and capecitabine (2,250 mg/m(2), orally in two daily divided doses, on days 1-7 and 15-21). All three drugs were administered in 4-week cycles, in an initial prospective plan of six cycles. The primary end-point was response rate. RESULTS: Forty patients were enrolled in the study. At the time of enrollment, 40% of patients had locally advanced and 60% metastatic disease. All patients were evaluable for response and toxicity. On an intent-to-treat analysis, the overall response and disease control rates were 40 and 80%, respectively. The median progression-free survival was 6.0 months, and the median overall survival was 9.0 months. Major grade 3/4 toxicities were neutropenia (17.5%), diarrhea (10%) and hand-foot syndrome (7.5%). There was no treatment-related death. CONCLUSION: The combination of gemcitabine with docetaxel and capecitabine is feasible and exhibits satisfactory degree of activity in patients with advanced pancreatic cancer, deserving further exploration.

Docetaxel plus oxaliplatin in combination with capecitabine as first-line treatment for advanced gastric cancer.

OBJECTIVE: In the present phase II study, we evaluated the efficacy and safety of a docetaxel-oxaliplatin-capecitabine combination as a first-line treatment in patients with advanced gastric cancer. PATIENTS AND METHODS: A total of 27 patients (18 males) with histologically confirmed inoperable gastric adenocarcinoma were recruited. Docetaxel was given (50 mg/m(2) i.v.) on day 1 followed by oxaliplatin (75 mg/m(2) i.v.) also on day 1. Capecitabine (2,750 mg/m(2)) was given orally as two daily divided doses from days 1 to 7. Cycles were repeated every 2 weeks. All patients had measurable disease and 18 of them had a performance status (WHO) of 0. RESULTS: A total of 240 treatment cycles were administered. All patients were evaluable for toxicity. Four patients who discontinued treatment early (having received only 3 chemotherapy cycles) were included as non-responders in an intention-to-treat response analysis. Complete response, partial response, stable disease and progressive disease were observed in 4 (15%), 12 (44%), 3 (11%) and 8 (30%) patients, respectively. The observed response rate was 59%, and the disease control rate (complete response + partial response + stable disease) was 70%. At the time of analysis, 6 patients were still alive and the median survival was 18.0 months. The most common grade III/IV toxicities observed were neutropenia (5%), diarrhea (2%), palmar-plantar erythrodysesthesia (2%) and neurotoxicity (1%). All other toxicities were mostly of grade I/II and easily manageable. CONCLUSION: The combination of docetaxel, oxaliplatin and capecitabine in the described mode of administration represents a relatively active and well-tolerated regimen in patients with advanced gastric cancer and warrants further evaluation.

Biweekly vinorelbine and gemcitabine as second-line and beyond treatment in ovarian cancer.

PURPOSE: To evaluate the activity and tolerance of vinorelbine (VRL) in combination with gemcitabine (GEM) in pre-treated patients with refractory ovarian cancer. PATIENTS AND METHODS: Seventeen patients with ovarian cancer who had disease progression after a carboplatin and taxane front-line regimen were treated with VRL 30 mg/m(2) IV over 10 min followed by GEM 1,200 mg/m(2) IV over 30 min on days 1 and 15 of each 28 days cycle. Chemotherapy was given in a initial prospective plan of six cycles, unless disease progression or unacceptable toxicity was seen, giving more cycles as consolidation therapy in the case of CR, PR or SD. The median age of patients was 67 years old, and the performance status (WHO) was 1 for 13 and 2 for 4 patients. The treatment was second-line for 11 (65%) and >third-line for 6 (35%) patients. RESULTS: One complete and one partial response were observed (ORR:11%). Stable disease was seen in 4 (24%) patients and progressive disease in 11 (65%). The median time to tumor progression was 4 months (range 2-11), and the median survival has not yet been reached. Myelotoxicity was rare. Grade 1 neutropenia was observed just in one patient and grade 2/3 anemia in four patients (24%). Thrombocytopenia was absent. Non-hematologic toxicity was also predictable and easily manageable. CONCLUSION: The vinorelbine plus gemcitabine combination at the present doses and schedule is a safe but ineffective regimen, and therefore, is not recommended as second-line and beyond treatment in patients with refractory ovarian cancer.

Biweekly vinorelbine and gemcitabine as second-line treatment and beyond in non-small cell lung cancer.

BACKGROUND: To evaluate the activity and tolerance of gemcitabine (GEM) in combination with vinorelbine (VRL) in pretreated patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifteen patients with advanced NSCLC who had disease progression after a cisplatin- or taxane-based front-line regimen were enrolled into a 2-stage design trial and were treated with VRL 30 mg/m² i.v. for 10 min followed by GEM 1,200 mg/m² i.v. for 30 min on days 1 and 15 of each 28-day cycle. Chemotherapy was given for 6 cycles unless disease progression or unacceptable toxicity was seen. The patients' median age was 64 years and the performance status (WHO) was 0 (n = 7), 1 (n = 5), and 2 (n = 3). The treatment was second line for 10 (67%) and third line or more for 5 (33%) patients. RESULTS: No complete or partial responses were observed. Stable disease was seen in 4 (27%) patients and progressive disease in 11 (73%). The median time to tumor progression was 3 months (range 1-12) and the median survival was 4 months (range 2-31). Severe myelotoxicity was infrequent. Grade 2 neutropenia was observed in 2 (13%) patients, grade 2 thrombocytopenia in 1 (7%), and grade 2 anemia in 3 (20%). Nonhematologic toxicities were very mild and easily manageable. CONCLUSION: The GEM plus VRL combination at the present doses and schedule is a safe but ineffective regimen; therefore, it is not recommended as second-line treatment in patients with advanced NSCLC.