title: Efficacy and tolerability of chemotherapy with modified dose-dense TCF regimen (TCF-dd) in locally advanced or metastatic gastric cancer: final results of a phase II trial.
abstract: BACKGROUND
  We previously studied a dose-dense TCF (TCF-dd) regimen demonstrating its feasibility and an activity comparable to epirubicin-based chemotherapy and TCF q3w in terms of overall survival and time to progression (TTP). We report here the final results of a phase II study of chemotherapy with a modified TCF-dd regimen in locally advanced or metastatic gastric cancer (MGC).
  
  
  METHODS
  Patients with histologically confirmed measurable MGC, not previously treated for advanced disease, received docetaxel 70 mg/m(2) day 1, cisplatin 60 mg/m(2) day 1, l-folinic acid 100 mg/m(2) days 1 and 2, followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus days 1 and 2, and then 600 mg/m(2) as a 22-h continuous infusion 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
  Study duration: December 2007-November 2010. Forty-six consecutive patients were enrolled (78 % male, 22 % female; median age, 66 years, range, 38-76 years; ECOG PS: 0, 48 %, 1, 46 %). Primary endpoint was overall response rate (ORR). A median of four cycles (range, one to six) was administered. Forty-three patients were evaluated for response (93.5 %) and all for toxicity: 3 complete response (CR), 25 partial response (PR), 10 stable disease (SD), and 5 progressive disease (PD) were observed, for an ORR by intention to treat (ITT) of 61 % (95 % CI 47-75). Median overall survival (OS) was 17.63 months (95 % CI, 13.67-20.67); median progression-free survival was 8.9 months (95 % CI, 6.5-13.4). Twenty-one patients (46.0 %) were treated at full doses without any delay, thus respecting the dose-dense criterion. Most frequent grade 3-4 toxicities were neutropenia (20 %), leukopenia (4 %), thrombocytopenia (2 %), anemia (2 %), febrile neutropenia (6 %), asthenia (22 %), diarrhea (4 %), nausea/vomiting (11 %), and hypokalemia (6 %). Overall, TCF-dd was shown to be safe.
  
  
  CONCLUSIONS
  The TCF-dd regimen in locally advanced or MGC is confirmed to be feasible and very active and needs to be further tested in randomized studies.
authors.affiliation: Medical Oncology Division, Azienda Istituti Ospitalieri di Cremona, Viale Concordia 1, 26100, Cremona, Italy, g.tomasello@ospedale.cremona.it.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
authors.forename: Wanda
authors.initials: W
authors.lastname: Liguigli
authors.forename: Rossana
authors.initials: R
authors.lastname: Poli
authors.forename: Silvia
authors.initials: S
authors.lastname: Lazzarelli
authors.forename: Matteo
authors.initials: M
authors.lastname: Brighenti
authors.forename: Federica
authors.initials: F
authors.lastname: Negri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Curti
authors.forename: Mario
authors.initials: M
authors.lastname: Martinotti
authors.forename: Lucio
authors.initials: L
authors.lastname: Olivetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Rovatti
authors.forename: Gianvito
authors.initials: G
authors.lastname: Donati
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Passalacqua
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim; D002945:Cisplatin; D005472:Fluorouracil