2012 Gastrointestinal Cancers Symposium
SAN FRANCISCO — Phase 3 results from the AMC 0101 study showed
patients treated with iceMFP chemotherapy for serosa-positive advanced gastric
cancer had superior outcomes when assigned to intraperitoneal cisplatin and/or
early start of chemotherapy.
Patients were assigned to Mf (20 mg/m2 of mitomycin-C and
daily oral 460-600 mg/m2 doxifluridine) or iceMFP (mitomycin-C and
doxifluridine plus cisplatin). Patients received 100 mg intraperitoneal
cisplatin for two hours during surgery, and 15 mg/m2 IV mitomycin-C
one day after surgery. Doxifluridine was administered 4 weeks after surgery for
a total of 12 months, along with six shots of monthly 60 mg/m2
As of April 2011, a median follow-up of 6.6 years, patients assigned to
iceMFP demonstrated superior 5-year recurrence-free survival (HR=0.73; 95% C.I.
0.57-0.93) and 5-year OS (HR=0.77; 95% C.I. 0.60-0.98) compared with patients
assigned to Mf chemotherapy.
That represented a 9% improvement in OS compared with 3-year results,
said Yoon-Koo Kang, MD, PhD, with the Asan Medical Center in Seoul,
“Considering that there was no benefit of adding cisplatin or
prolonging oral doxifluridine to Mf chemotherapy in AMC 0201, early start of
chemotherapy and/or intraperitoneal cisplatin seem to be responsible for the
improved efficacy of iceMFP chemotherapy in this study,” he said.
A total of 521 patients were eligible for intent-to-treat analysis
— 258 in the Mf group and 263 in the iceMFP group. One-third of patients
had stage II disease after surgery, 31.9% had stage IIIA; 17.5% had stage IIIB
disease; and 17.3% of patients had stage IV disease.
Researchers launched the phase-3 PRODIGY study last year based on
results from AMC 0101 and AMC 0201, Kang said. That trial will compare results
from patients assigned to neoadjuvant docetaxel and oxaliplatin, plus surgery
S-1 vs. surgery plus adjuvant S-1. The primary endpoint is
3-year PFS. – by Jason Harris
Disclosure: Dr. Kang reported no relevant financial disclosures.
This study showed that the addition of IP cisplatin chemotherapy and
early administration of chemotherapy may be helpful as adjuvant chemotherapy in
resected gastric cancer, since this regimen showed a 9% improvement in OS.
Since intravenous chemotherapy did not give a similar result, one would need to
conclude that the benefit can be attributed to giving the drug
intraperitoneally. However, an earlier JCOG trial (92002) did not show such
benefit with IP chemotherapy, so additional trials are needed. Furthermore, it
may be useful to determine if the two populations are actually different by
molecular analysis, thus explaining the discordant results.
Susan J. Littman, MD
Assistant professor of
Jefferson's Kimmel Cancer Center, Philadelphia
Disclosure: Dr. Littman reports no relevant financial