Docetaxel, Cisplatin, 5-Fluorouracil compare to Cisplatin and 5-fluorouracil for chemotherapy-naive patients with metastatic or locally recurrent, unresectable gastric carcinoma (MGC): Interim results of a randomized phase III trial (V325)
Reviewer: Tracy d'Entremont, MD
Last Modified: June 2, 2003
Presenter: J. A. Ajani Presenter's Affiliation: MD Anderson Cancer Center; Houston , TX Type of Session: Scientific
Gastric cancer is the 2nd most frequent world wide malignancy and is the 2nd most frequent cause of cancer deaths world wide.
MGC is incurable with a median survival of 6-9 months
Docetaxel, Cisplatin and 5-FU (DCF)is an active regimen against MGC
The first portion of V325 was a randomized phase II trial comparing DCF vs. DC. An Independent Data Monitoring Committee chose the DCF arm as the most active regimen and designated it as the test arm for the second portion of V325
Materials and Methods
For this second portion of V325, 460 patients with MGC or locally unresectable GC were randomized to receive either DCF or Cisplatin, 5-FU (CF) which is the standard reference regimen.
Patients were stratified based on liver metastases, prior surgery, measurability, and >5% wt loss in the prior 3 months.
The primary endpoint was TTP
Secondary endpoints include: OS, RR and safety
In order to have 90% power to detect an increase in TTP from 4 mos to 6 mos, 325 events were needed. This is a planned interim analysis that was conducted after 50% of the events have occurred or 162 events.
Because of the interim analysis, the authors correctly used more stringent p-values.
The chemotherapy regimens were as follows:
DCF: Docetaxel 75 mg/m2 d1, Cisplatin 75 mg/m2 d1, 5-FU 750 mg/m2/d by cont iv infusion, days 1-5 q3weeks
CF: Cisplatin 100mg/m2 d1, 5-FU 1000mg/m2/d cont iv infusion d1-5 q4weeks
Patients in the experimental arm completed more cycles of chemotherapy than those in the control arm (6 vs 4).
Dose intensity for 5-FU and cisplatin was equivalent in both arms
CR was equivalent in both arms (2.7%)
PR was higher in the DCF arm (36% vs. 20.5%)
Therefore overall RR was higher in the DCF arm (38.7% vs. 23%)
TTP was significantly longer in the DCF arm (5.2 mos vs. 3.7mos) p=0.0008
PFS at 6 months was 45.9% for DCF and 26% for CF
Median OS was 10.2 months for DCF and 8.5 for CF with a p=.0064 (n.s.)
Toxicity in the DCF arm was slightly higher with more febrile neutropenia and more neutropenic infections. However, the overall toxic death rate was equivalent in both arms at 6.3% and the 30 day all cause mortality was equivalent in both arms at (2.3-3.1%)
The author's conclude that DCF has an improved TTP and RR when compared with CF. They predict that with full analysis of all patients and events, the OS difference will become statistically significant.
They report that the myelotoxicity is predictable and manageable.
They claim that DCF should now be the "standard" 1st line regimen for locally advanced or metastatic gastric cancer.
This data is clearly intriguing with improved TTP and a trend towards improved OS.
The toxicities however cannot be overlooked. One could argue that the rate of myelosuppression was so significant that growth factor support should have been offered up front, which it was not.
Quality of Life endpoints are reportedly being taken and this information will be very important to evaluate. Afterall, living longer but with significant toxicity and decreased quality of life is rarely a choice most patients would make.
We are cautiously optimistic that this regimen may infact prove to be more useful than CF, however we await the final data before this regimen becomes standard.
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