Split-dose Docetaxel, Cisplatin and Leucovorin/fluorouracil
Split-dose Docetaxel, Cisplatin and Leucovorin/fluorouracil
Background: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but high rates of hematologic toxicity in advanced gastric cancer. To reduce toxicity while maintaining the efficacy of DCF, we investigated split doses of docetaxel (T), cisplatin (P), leucovorin (L) and fluorouracil (F).
Patients and methods: Chemotherapy-naive patients with advanced gastric-/esophageal adenocarcinomas received T 50 mg/m and P 50 mg/m on days 1, 15 and 29 and L 500 mg/m plus F 2000 mg/m weekly, every 8 weeks. Because significant dose reductions to <80% became necessary in 80% of patients, the regimen was amended after the first 15 patients to T 40 mg/m, P 40 mg/m, L 200 mg/m and F 2000 mg/m. The primary endpoint was response rate.
Results: Sixty patients were enrolled: 24 had locally advanced (LA) tumors and 36 had metastatic disease. Grade 3/4 toxicities included neutropenia (22%), febrile neutropenia (5%), diarrhea (20%) and lethargy (18%). The overall response rate was 47%. Twenty-three LA patients underwent secondary surgical resection (96%); complete resection was achieved in 87%. Overall, median time to progression and overall survival were 9.4 and 17.9 months, respectively (8.1 and 15.1 months, respectively, for patients with metastatic disease).
Conclusion: T-PLF regimen is highly active and has a favorable toxicity profile.
Advanced gastric and gastroesophageal cancer remains one of the leading causes of death by neoplasia worldwide. While current fluorouracil- and cisplatin-based combination chemotherapy regimens confer a survival benefit when compared to best supportive care, outcomes remain suboptimal.
In phase II studies, docetaxel has shown activity against gastric and gastroesophageal cancer as both monotherapy and as part of combination chemotherapy. In patients with untreated gastric cancer, the triple combination docetaxel-cisplatin-fluorouracil (DCF) is superior in terms of response rate to docetaxel-cisplatin (DC), epirubicin-cisplatin-fluorouracil and cisplatin-fluorouracil (CF). Results of the V325 trial demonstrate that the addition of docetaxel to CF results not only in a higher response rate, but also a prolonged time to progression (TTP) and overall survival (OS), improved quality of life and greater clinical benefit. However, the high incidence of grade 3-4 neutropenia (82%) and febrile neutropenia (29%) observed in this study remains a concern.
To improve tolerability while maintaining the efficacy of the DCF regimen, the optimal dosing and scheduling of docetaxel-based chemotherapy needs to be refined. Phase I and II studies have demonstrated that the tolerability profile of docetaxel can be improved markedly when it is administered on a weekly schedule. With weekly administration, complicated neutropenia as a result of myelosuppression is rarely reported. A split-dose regimen, with biweekly scheduling of docetaxel and cisplatin, may be a more tolerable regimen.
We performed a phase II trial to investigate the efficacy and safety of the split-dose docetaxel, cisplatin, leucovorin and fluorouracil regimen (T-PLF) in untreated patients with locally advanced (LA) or metastatic gastric cancer or adenocarcinoma of the esophagogastric junction.
Background: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but high rates of hematologic toxicity in advanced gastric cancer. To reduce toxicity while maintaining the efficacy of DCF, we investigated split doses of docetaxel (T), cisplatin (P), leucovorin (L) and fluorouracil (F).
Patients and methods: Chemotherapy-naive patients with advanced gastric-/esophageal adenocarcinomas received T 50 mg/m and P 50 mg/m on days 1, 15 and 29 and L 500 mg/m plus F 2000 mg/m weekly, every 8 weeks. Because significant dose reductions to <80% became necessary in 80% of patients, the regimen was amended after the first 15 patients to T 40 mg/m, P 40 mg/m, L 200 mg/m and F 2000 mg/m. The primary endpoint was response rate.
Results: Sixty patients were enrolled: 24 had locally advanced (LA) tumors and 36 had metastatic disease. Grade 3/4 toxicities included neutropenia (22%), febrile neutropenia (5%), diarrhea (20%) and lethargy (18%). The overall response rate was 47%. Twenty-three LA patients underwent secondary surgical resection (96%); complete resection was achieved in 87%. Overall, median time to progression and overall survival were 9.4 and 17.9 months, respectively (8.1 and 15.1 months, respectively, for patients with metastatic disease).
Conclusion: T-PLF regimen is highly active and has a favorable toxicity profile.
Advanced gastric and gastroesophageal cancer remains one of the leading causes of death by neoplasia worldwide. While current fluorouracil- and cisplatin-based combination chemotherapy regimens confer a survival benefit when compared to best supportive care, outcomes remain suboptimal.
In phase II studies, docetaxel has shown activity against gastric and gastroesophageal cancer as both monotherapy and as part of combination chemotherapy. In patients with untreated gastric cancer, the triple combination docetaxel-cisplatin-fluorouracil (DCF) is superior in terms of response rate to docetaxel-cisplatin (DC), epirubicin-cisplatin-fluorouracil and cisplatin-fluorouracil (CF). Results of the V325 trial demonstrate that the addition of docetaxel to CF results not only in a higher response rate, but also a prolonged time to progression (TTP) and overall survival (OS), improved quality of life and greater clinical benefit. However, the high incidence of grade 3-4 neutropenia (82%) and febrile neutropenia (29%) observed in this study remains a concern.
To improve tolerability while maintaining the efficacy of the DCF regimen, the optimal dosing and scheduling of docetaxel-based chemotherapy needs to be refined. Phase I and II studies have demonstrated that the tolerability profile of docetaxel can be improved markedly when it is administered on a weekly schedule. With weekly administration, complicated neutropenia as a result of myelosuppression is rarely reported. A split-dose regimen, with biweekly scheduling of docetaxel and cisplatin, may be a more tolerable regimen.
We performed a phase II trial to investigate the efficacy and safety of the split-dose docetaxel, cisplatin, leucovorin and fluorouracil regimen (T-PLF) in untreated patients with locally advanced (LA) or metastatic gastric cancer or adenocarcinoma of the esophagogastric junction.
