Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer
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Gemma Bruera1,2, Silvia Massacese3, Antonio Galvano4, Antonella Dal Mas5, Stefano Guadagni6,2, Giuseppe Calvisi5, Eugenio Ciacco3, Antonio Russo4, Enrico Ricevuto1,2, on behalf of Oncology Network ASL1 Abruzzo, Italy
1Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy
2Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
3Pharmacy Unit, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L’Aquila, Italy
4Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
5Pathology, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, L'Aquila, Italy
6Universitary General Surgery, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy
Antonio Russo, email: email@example.com
Keywords: docetaxel, 5-fluorouracil, and oxaliplatin; FD/FOx intensive regimen; dose-finding study; first-line triplet chemotherapy; metastatic gastric cancer
Received: January 24, 2018 Accepted: March 07, 2018 Published: April 17, 2018
Introduction: Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity.
Methods: Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m2/d 1-2, 8-9, 15-16, 22-23, with 100 mg/m2/d increase for dose level; DTX 50 mg/m2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned.
Results: Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m2/d and 80 mg/m2, respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively.
Conclusions: First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.
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