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

Background: Previous studies reported that in lymphomas, early breast and bladder cancer, dose-dense CT is more effective than conventional treatment. We reported for the first time, in 2006 ASCO meeting, the feasibility of an intensified dose-dense TCF regimen (q2w) in MGC. This is the subsequent phase II study. Methods: patients (pts) with histologically confirmed measurable MGC, ECOG PS 0–3, received up to 6 cycles of Docetaxel 85 mg/m2 (75 mg/m2 after first 12 pts, 70 mg/m2 after the 28th patient) day 1, Cisplatin 75 mg/m2 day 1 (60 mg/m2 after the 28th patient) l-Folinic Acid 100 mg/m2 day 1 and 2, followed by 5-Fluorouracil 400 mg/m2 bolus day 1 and 2, and then 600 mg/m2 as a 22 hour continuous infusion day 1 and 2, every 14 days, plus Pegfilgrastim 6 mg on day 3. Pts with a PS > 1 and/or age > 65 years and/or pre-treated for the metastatic disease, received the same schedule with a dose reduction by 30%. Results: 31 consecutive pts were enrolled (81% male, 19% female; median age: 60, range 40–79; median ECOG PS: 1, range 0–3; 3 pts pre-treated). Primary end points were response rate and safety. A median of 4 cycles (range 1–6) per pts were administered. 15 pts (48%) required a dose reduction, mostly because of hematologic toxicity and severe asthenia. 10 pts (32%) were treated with full dose without any delay on at least the first 4 cycles. 25 pts were evaluated for response (3 too early, 1 early suspension because of severe allergic reaction to Docetaxel; 2 early deaths: 1 bowel perforation and 1 sepsis) and 30 for toxicity. 2 CR (multiple liver metastases), 12 PR, 4 SD and 7 PD were observed, for an ORR (RECIST criteria and intention-to-treat principle) of 50% (95% CI 30–65). At a median follow-up of 10 months (range 1–24), overall median survival was 6 months (range 1–20). Frequent grade 3 to 4 toxicities were: neutropenia (65%), thrombocytopenia (31%), anemia (14%) febrile neutropenia (31%), asthenia (62%), diarrhoea (21%) and stomatitis (14%). Conclusions: TCF-DD regimen in MGC is feasible and very active. The recommended dose (with reduction by 30% as above) for further randomised studies comparing TCF-DD with standard TCF is Cisplatin 60 mg/m2 and Docetaxel 70 mg/m2