Phase 2 Study of Capecitabine and Irinotecan Combination Chemotherapy (Modified XELIRI Regimen) in Patients With Advanced Gastric Cancer
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Guangzhou, People's Republic of China. American journal of clinical oncology
(Impact Factor: 3.06).
12/2011; 34(6):555-60. DOI: 10.1097/COC.0b013e3181f47ac1
The prognosis of patients with advanced gastric cancer (AGC) remains poor, and no single chemotherapy regimen is recognized as a global standard. A phase 2 trial was conducted to determine the efficacy and tolerability of the modified combination regimen of capecitabine and irinotecan (mXELIRI) in patients with AGC.
Patients with earlier untreated AGC received intravenous irinotecan (125 mg/m) over 90 minutes on days 1 and 8, and oral capecitabine (850 mg/m) twice daily on days 2 to 15, every 3 weeks. Treatment was continued for at most 8 cycles or until disease progression or intolerable toxicity.
Thirty-two patients were enrolled. In total, 141 cycles of mXELIRI were administered. The overall response rate was 43.7%, with 1 complete response and 13 partial responses. At a median follow-up of 16.2 months, median time to progression and overall survival were 5.6 months (95% confidence interval, 4.27-6.93 mo) and 11.0 months (95% confidence interval, 8.71-13.29 mo), respectively. The most common hematological adverse event was neutropenia (n=18, 56.3%); grade 3 neutropenia was observed in 5 patients, with neutropenic fever in only 2 patients. The most common grade 3/4 nonhematological toxicities were anorexia (n=3, 9.4%), nausea (n=3, 9.4%), vomiting (n=2, 6.3%), and diarrhea (n=2, 6.3%). There was no treatment-related death.
mXELIRI is a safe and effective first-line treatment for unresectable and metastatic gastric cancer with a manageable tolerability profile. It can be used as one of the first-line treatment options for patients with AGC.
Available from: PubMed Central
- "As recommended by the guidelines of the National Comprehensive Cancer Network, patients were allocated to FU-based treatment. FOLFIRI, irinotecan (Camptosar; Pfizer) 180 mg/m2 intravenous (IV) infusion over 30–90 minutes, day 1; leucovorin 400 mg/m2 IV infusion to match the duration of irinotecan infusion, day 1; 5-FU 400 mg/m2 IV bolus, day 1; then 1200 mg/m2/day × 2 days (total 2400 mg/m2 over 46–48 hours) continuous infusion; repeat every 14 days or mCapeIRI35 regimen (irinotecan 125 mg/m2, days 1 and 8; capecitabine (Xeloda; Roche)825–1000 mg/m2, twice daily on days 1–14; repeat every 21 days) or FOLFOX (oxaliplatin 80 mg/m2 IV infusion over 2 hours, day 1; leucovorin 400 mg/m2 IV over 2 hours, day 1; 5-FU 400 mg/m2 IV bolus, day 1; then 1200 mg/m2/day × 2 days continuous infusion; repeat every 14 days) or CapeOX (Oxaliplatin 130 mg/m2 day 1, Capecitabine 825–1000 mg/m2, twice daily on days 1–14; repeat every 21 days) or single-agent chemotherapy of capecitabine (1250 mg/m2 twice daily on days 1–14; repeat every 21 days). All patients accepted 5-hydroxytryptamine receptor antagonist (5 mg once a day) 30–60 minutes before irinotecan or oxaliplatin. "
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ABSTRACT: The predictive value of thymidine phosphorylase gene variants (TP, also called platelet-derived endothelial cell growth factor) and thrombocytosis were controversial and worthy of further study in gastrointestinal cancer (GIC) patients. We screened all of the common missense single nucleotide polymorphisms (MAF ≥ 0.1) in fluoropyrimidines (FU) pathway genes (including TP, TS, ENOSF1 and DPD). Three of them were selected and genotyped using Sequenom MassARRAY in 141 GIC patients. TP expression was assessed by immunohistochemistry. Our aim was to evaluate the prognostic significance of studied genes and platelet counts in GIC patients. Multivariate analyses indicated in rs11479-T allele carriers, platelet counts negatively correlated to overall survival. In addition, T allele of TP: rs11479 was associated with higher TP expression in cancer tissues. We suggest TP: rs11479 variant combined with platelet counts may be useful prognostic makers in GIC patients receiving first-line FU chemotherapy and thrombopoietin factor should be used with caution in the rs11479 T allele bearing patients.
Available from: Miao-Zhen Qiu
- "The dose intensity of S-1 in our included studies ranged from 168 to 560 mg/m2/week, between that of FLAGS trial (262.5mg/m2/week) and SPIRITS trial (doublet arm, 336 to 504 mg/m2/week) in most cases, conforming to that the ORR here is between that of FLAGS trial and SPIRITS trial (doublet arm). Similarly, the pooled ORR (39.1%) and ORR of capecitabine-based therapy (13.3% to 55.0%) were consistent with those in the one-arm phase 1/2 clinical trials of capecitabine-based chemotherapy (23.5% to 62.2%) [44-47], the capecitabine-based arm of RCT including ML17032 trial and REAL-2 trial (35% to 48%) [12,13], and the capecitabine-based arm of the meta-analysis comparing capecitabine and 5-FU (45.6%) [14,15]. The regimen of the REAL-2 trial was capecitabine (7000mg/m2/week) plus platinum (cisplatin 20 mg/m2/week or oxaliplatin 43.3 mg/m2/week) plus epirubicin. "
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ABSTRACT: Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC.
PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model.
Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% conﬁdence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There're no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed.
S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared with capecitabine-based therapy. We recommended S-1 and capecitabine can be used interchangeably for AGC, at least in Asia.
Available from: Conghua Xie
- "The patients who accepted FOLFIRI received, as recommended by the guidelines of the National Comprehensive Cancer Network, irinotecan (Camptosar; Pfizer, Sydney, Australia) 180 mg/m2 intravenous (IV) infusion over 30–90 minutes, day 1; leucovorin 400 mg/m2 IV infusion to match the duration of irinotecan infusion, day 1; 5-FU 400 mg/m2 IV bolus, day 1; then 1200 mg/m2/day × 2 days (total 2400 mg/m2 over 46–48 hours) continuous infusion; this was repeated every 14 days. Patients who declined continuous infusion were later changed to an mCapeIRI regimen (irinotecan 125 mg/m2, days 1 and 8; capecitabine 825–1000 mg/m2, twice daily on days 1–14; repeat every 21 days). We modified the standard irinotecan plus capecitabine (CapeIRI or XELIRI) regimen because of our experience in toxicity control. "
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ABSTRACT: Rapid response to chemotherapy in metastatic colorectal cancer (mCRC) patients (response within 12 weeks of chemotherapy) may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs) in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens.
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