Randomized phase III trial of capecitabine/cisplatin (XP) vs. continuous infusion of 5-FU/cisplatin (FP) as first-line therapy in patients (pts) with advanced gastric cancer (AGC): Efficacy and safety results

Abstract

LBA4018 Background: The oral fluoropyrimidine capecitabine has proven efficacy and safety in colorectal and breast cancer. Phase II data in AGC suggested that XP would show comparable efficacy to a standard FP regimen, with potential safety and convenience advantages. This phase III study evaluated XP vs. FP in first-line AGC. Methods: Pts with previously untreated measurable AGC received either oral capecitabine (1000mg/m2 bid d1–14) + cisplatin (80mg/m2 i.v. d1) q3w (XP arm) or 5-FU (800mg/m2/d continuous infusion, d1–5) + cisplatin (80mg/m2 i.v. d1) q3w (FP arm). XP requires 1 day per 3 weeks in hospital; FP requires 5 days. Pts were treated until disease progression or unacceptable toxicity. Primary endpoint: non-inferiority (NI) in progression-free survival (PFS), defined as upper limit of 95% CI of hazard ratio (HR) <1.4 (first test) and <1.25 (second test). Results: From Apr 03 to Jan 05, 316 pts were enrolled in 46 centers/13 countries. Arms were well balanced: median age (years, range) XP (56, 26–74), FP (56, 22–73); median Karnofsky PS 80 (range 70–100) in both arms; male/female (%): XP (64/36) FP (69/31). Median no. of cycles was 5 (XP and FP). Median follow-up is 22.1 months. Primary endpoint was met: HR 0.81 (95% CI 0.63–1.04). XP was superior to FP in terms of overall response rate (ORR, RECIST). Efficacy is presented in the table. Most common treatment-related grade 3/4 adverse events (XP vs. FP) were: neutropenia (16 vs. 19%), vomiting (7 vs. 9%), stomatitis (2 vs. 7%), diarrhea (5 vs. 5%), and anemia (5 vs. 3%). Other grade 3/4 events occurred in <5% of pts. The rate of all-grade hand-foot syndrome was low (22 vs. 4%). Conclusions: XP showed highly significant non-inferiority for PFS and significant superiority for ORR vs. FP with similar safety. These findings suggest that capecitabine should become the fluoropyrimidine of choice for AGC, given the efficacy, reduced hospitalization time and simplified regimen. No significant financial relationships to disclose. [Table: see text]

Capecitabine to Reduce Nonmelanoma Skin Carcinoma Burden in Solid Organ Transplant Recipients

“…[18][19][20] Capecitabine is as effective as 5-FU and has a better side-effect profile. 21 Recently, in a study of four non-SOTR patients, 950 mg/m 2 of oral capecitabine administered on days 1 to 14 of a 21day cycle along with three times weekly subcutaneous interferon alpha for advanced cutaneous SCC resulted in a complete response in two patients and partial response in the other two after three cycles; side effects were mild, and there was no change in patient status. 22 Given that SOTRs often have comorbidities and use several systemic medications, we were interested in the effect of low-dose cycled capecitabine on incident SCC.…”

Phase II study of S‐1 and irinotecan combination chemotherapy as a first‐line therapy for patients with advanced gastric cancer. Korean Cancer Study Group Protocol ST05‐02

“…Kang et al. reported the results of a phase III study that compared the XP and FP regimens 31 . The XP regimen showed no an inferior progression‐free survival (PFS) (5.6 months vs 5.0 months, respectively) and showed a superior response rate (41 vs 29%, respectively), with similarly favorable safety profiles compared with FP, as well as being more convenient than FP.…”

Clinical development of S-1 plus cisplatin therapy as first-line treatment for advanced gastric cancer

“…In the phase II portion, the effi cacy and safety of the regimen was evaluated in 19 patients, including 6 patients in the RD level in the phase I portion. The median number of cycles administered was four (range, [1][2][3][4][5][6][7][8]. The incidences of grade 3 or more hematological and nonhematological toxicities were 15.8% and 26.3%, respectively, but all were manageable.…”

“…Outcomes are extremely poor among patients with unresectable gastric cancer, with the median survival ranging from 3 to 5 months with the best supportive care [4][5][6].Randomized controlled trials of various treatment regimens have produced disappointing results in patients with advanced gastric cancer (AGC), with survival of only 6 to 11 months. Median survival times (MSTs) have gradually improved, but are still less than 1 year [7][8][9][10][11][12][13]. Standard treatments remain a matter of debate.In this context, we evaluated the effectiveness of S-1 plus cisplatin (CDDP) therapy in a randomized phase III study based on the promising activity of several clinical studies of S-1.…”

“…Randomized controlled trials of various treatment regimens have produced disappointing results in patients with advanced gastric cancer (AGC), with survival of only 6 to 11 months. Median survival times (MSTs) have gradually improved, but are still less than 1 year [7][8][9][10][11][12][13]. Standard treatments remain a matter of debate.…”