Dose-dense Chemotherapy in Metastatic Gastric Cancer with a Modified Docetaxel-Cisplatin-5-Fluorouracil Regimen

Abstract

Aims and background

Previous studies have reported that in early breast cancer, lymphomas and advanced bladder cancer, dose-dense chemotherapy may be more effective than conventional treatments. In metastatic gastric cancer, chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TCF) q3w is very active, and, even though there is no international consensus on the subject, it is the regimen of choice of many European centers as first-line chemotherapy in this subset of patients. 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-fluorouracil infusion with l-folinic acid/5-fluorouracil according to the “De Gramont regimen”.

Methods and study design

Patients with histologically confirmed measurable metastatic gastric cancer, ECOG performance status ≤1, and not previously treated for advanced disease received docetaxel, 85 mg/m² (75 mg/m² after the first 6 patients, 70 mg/m² after the 19^th patient) on day 1, cisplatin, 75 mg/m² on day 1 (60 mg/m² after the 19th patient), l-folinic acid, 100 mg/m² on days 1 and 2, followed by 5-fluorouracil, 400 mg/m² bolus on days 1 and 2 and then 600 mg/m² as a 22-h continuous infusion on days 1 and 2, every 14 days, plus pegfilgrastim, 6 mg on day 3. Patients aged ≥65 years received the same schedule with a dose reduction of 30%.

Results

Thirty-two consecutive patients were enrolled (63% male, 37% female); median age, 64 years (range, 40–81). A median of 4 cycles (range, 1–7) per patient was administered. Eleven of 32 patients (34%) required a dose reduction, mostly for hematological grade III-IV toxicity and severe asthenia. Twelve patients (38%) completed the first 4 cycles of therapy within 7 weeks, thereby finishing without delay the initially planned dose-density schedule. Twenty-eight patients were evaluated for response (1 early suspension after the first cycle because of toxicity, 3 deaths before response evaluation due to progression of disease). There were 3 complete responses (9%), 15 partial responses (47%), 7 stable disease (22%) and 3 progression of disease (9%), for an overall response rate, by intention to treat, of 56% (95% CI, 39–73). The most frequent grade 3–4 toxicities were: neutropenia (53%), thrombocytopenia (34%), anemia (16%) febrile neutropenia (22%), asthenia (38%) and diarrhea (19%). Median time to progression was 9.1 months (95% CI, 6.0–12.2); median overall survival was 10.1 months (95% CI, 8.8–12.2).

Conclusions

A dose-dense TCF regimen in metastatic gastric cancer is feasible, with activity comparable to previous results achieved with epirubicin-based chemotherapy and TCF q3wk in terms of overall survival and time to progression, and deserves to be further tested in randomized phase III studies.