Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group.
OBJECTIVE
For patients with advanced gastric or gastroesophageal cancer (AGGEC) providing clinical benefit with improved palliation is highly desirable. However, a prospective evaluation of clinical benefit in AGGEC patients has never before been reported in a phase III setting.


METHODS
In a multinational trial (V325), 445 patients were randomly assigned and treated with either docetaxel plus cisplatin and fluorouracil (DCF) or cisplatin and fluorouracil (CF). Clinical benefit was prospectively evaluated in this trial as a secondary end point. The primary measure for clinical benefit analysis was time to definitive worsening by one or more categories of Karnofsky performance status (KPS). Secondary clinical benefit end points included time to 5% definitive weight loss, time to definitive worsening of appetite by one grade, pain-free survival (defined as time to first appearance of pain), and time to first cancer pain-related opioid intake. Clinical benefit assessments were recorded at each clinic visit.


RESULTS
Clinical benefit assessments were performed in more than 75% of patients throughout V325. DCF significantly prolonged time to definitive worsening of KPS compared with CF (median, 6.1 v 4.8 months; hazard ratio, 1.38; 95% CI, 1.08 to 1.76; log-rank P = .009). Although time to definitive weight loss and time to definitive worsening of appetite favored DCF, the results were not statistically significant. Pain-free survival and time to first cancer pain-related opioid intake were comparable.


CONCLUSIONS
To our knowledge, V325 is the first phase III trial to report clinical benefit in AGGEC patients. Clinical benefit was assessed beyond protocol-specific chemotherapy. The addition of D to CF not only significantly improved clinical benefit but also improved quality of life, time to progression, and overall survival compared with CF.
Ajani
Jaffer A
JA
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. jajani@mdanderson.org
Moiseyenko
Vladimir M
VM
Tjulandin
Sergei
S
Majlis
Alejandro
A
Constenla
Manuel
M
Boni
Corrado
C
Rodrigues
Adriano
A
Fodor
Miguel
M
Chao
Yee
Y
Voznyi
Edouard
E
Marabotti
Cindy
C
Van Cutsem
Eric
E
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011788:Quality of Life; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil