Dose-dense chemotherapy with modified TCF regimen (TCF-DD) in metastatic gastric cancer (MGC): A feasibility study

Background: Previous studies reported that in early breast cancer, lymphomas and bladder, dose-dense chemotherapy is more effective than conventional treatments. In MGC chemotherapy with Docetaxel, Cisplatin and 5-FU (TCF) q3w is very active. Based on these studies, we tested for the first time the feasibility and activity of an intensified dose-dense TCF regimen (q2w) modifying the 5-FU continuous infusion with Folinic Acid/5-FU, according to the “De Gramont regimen.” Methods: patients (pts) with histologically confirmed measurable MGC, ECOG PS 0–3 received up to six cycles of Docetaxel 85 mg/m2 day (d) 1, Cisplatin 75 mg/m2 d 1, L-Folinic Acid 100 mg/m2 d 1 and 2, followed by 5-FU 400 mg/m2 bolus d 1 and 2 and then 600 mg/m2 as a 22-hour continuous infusion d 1 and 2, every 14 days, plus Granulocyte-Colony Stimulating Factor 5 μg/kg/d, from day 4 to 10 of each cycle or pegfilgrastim 6 mg on day 3. Pts with a PS > 1 and/or age > 65 years and/or pre-treated for the advanced disease, received the same schedule with a dose reduction by 30%. Results: 16 consecutive pts were enrolled (81% male, 19% female; median age: 60, range 40–79; median ECOG PS:1, range 0–3). Two pts received previously chemotherapy for the advanced disease. A median of 4 cycles (range 1–6) per patient were administered. Eleven pts were evaluated for response (3 too early, 2 early deaths) and 13 for toxicity; 1 CR (multiple liver metastases), 6 PR, 2 SD and 2 PD were observed, for an overall disease control rate, by intention to treat, of 69% (95% CI 44–95). No treatment delays were observed in 5 pts (PS 0–1, < 65 years old and all but one chemo-naïve); 8 pts did not respect the schedule (4 had PS >1, two of whom were > 65 years old; 4 were > 65 years old with PS 0–1). Grade 3/4 neutropenia (all not febrile), thrombocytopenia, and anemia occurred in 61%, 23% and 0% of pts, respectively. Grade 3/4 nausea/vomiting occurred in 15%. Conclusion: A dose-dense TCF regimen in MGC is feasible and active and deserves to be tested in randomised studies.