IP cisplatin, early start of chemotherapy associated with improved efficacy of iceMFP chemotherapy
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 cisplatin.
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, South Korea.
“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 and adjuvant 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 medical oncology
Jefferson's Kimmel Cancer Center, Philadelphia
Disclosure: Dr. Littman reports no relevant financial disclosures.
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