Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: results of a phase II trial

Purpose To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Patients and methods Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m² and cisplatin initially 75 mg/m² on day 1 [later modified due to toxicity: 70 and 60 mg/m² respectively], l-folinic acid 100 mg/m² on days 1 and 2, 5-fluorouracil 400 mg/m² bolus and then 600 mg/m² as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m², irinotecan 140 mg/m², l-folinic acid 200 mg/m², 5-fluorouracil bolus 400 mg/m² on day 1 followed by 2,400 mg/m² as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Results Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. Conclusions A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.