A Phase I Study of Irinotecan, Capecitabine (Xeloda), and Oxaliplatin in Patients With Advanced Colorectal Cancer

Maroun, J.; Marginean, Horia; Jonker, Derek J.; Cripps, C.; Goel, Rakesh; Asmis, Timothy R.; Goodwin, Rachel; Chiritescu, G.

doi:10.1016/j.clcc.2017.12.003

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…38 For the 3-week mode of the XELOXIRI regimen, the recommended RP2D for the Canadian phase I Maroun study was oxaliplatin 100 mg/m2, d1, capecitabine 1900 mg/m2/d in 2 divided doses, d2-15, and irinotecan 160 mg/m2, d1. 39 Considering the essential characteristics and safe tolerability of the Asian population and the fact that most patients were not tested for the UGA1T1 gene, capecitabine, oxaliplatin, and irinotecan were moderately reduced in this study. 15 patients achieved TRG 0-1, 22 patients achieved TRG 2-3, and 28 pathological Of the TRG scores not provided in the report, 8 cases ypT2N0, 2 cases ypT1N0,1 case pCR， which may be due to the effect of triple chemotherapy.…”

Section: Discussionmentioning

confidence: 96%

Capecitabine, Oxaliplatin, and Irinotecan (XELOXIRI) as Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Xiao

Zhang

2023

JSRMBS

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Purpose: This study describes the efficacy and safety of irinotecan and oxaliplatin in combination with capecitabine (XELOXIRI) as a neoadjuvant chemotherapy (NAC) regimen for patients with locally advanced rectal cancer (LARC). Methods: From January 2019 through December 2022, 68 LARC patients treated with XELOXIRI were enrolled in the study. XELOXIRI is administered in a three-week cycle consisting of oxaliplatin 70-110 mg/m2 IV for >120 min on day 1; irinotecan 120-160 mg/m2 IV for 90 min on day 1; and capecitabine 700-1100 mg/m2 orally twice daily for 14 days followed by 7 days off. Sixteen cases were treated with combined radiotherapy, including 8 with long-course radiotherapy and 8 with short-course radiotherapy. The efficacy was evaluated based on pelvic MRI (including TNM stage, CRM, and EMVI status), tumor downstaging rate (to ypT0-2N0M0), pCR rate, R0 resection rate, DFS, and OS, and the safety was assessed according to the incidence of adverse events. Results: Sixty-six people had surgery; the R0 resection rate was 100%, and the rate of anal preservation was 97%. The tumor downstaging rate (to ypT0-2N0M0) in the entire group was 53.0%, and the pCR rate was 12.1%. In the XELOXIRI alone group (N = 47), the tumor downstaging rate was 55.3%, and the pCR rate was 12.8%. In the group receiving radiotherapy (N = 16), the tumor downstaging rate was 56.3%, and the pCR rate was 12.5%. In the whole group, the 3-year DFS was 89.0%, and the 3-year survival rate was 98.5%. The 3-year DFS of the XELOXIRI and XELOXIRI + RT groups was 89.9% and 87.2%, respectively. The most frequent grade 3–4 preoperative toxic reactions were neutropenia (8.8%), diarrhea (4.4%), and anemia (2.9%). All adverse events were tolerable. Conclusions: Neoadjuvant chemotherapy with XELOXIRI appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate as NAC for LARC, tumor downstaging, R0 resection, sphincter preservation, local recurrence rate, 3-year DFS, OS, and safety were all satisfactory.

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Section: Discussionmentioning

confidence: 96%

Capecitabine, Oxaliplatin, and Irinotecan (XELOXIRI) as Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Xiao

Zhang

2023

JSRMBS

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“…At the same time, the pH is used as a trigger mechanism, verified by the coiling of alginate chains and their collapse under acidic conditions, creating a physical barrier in the GI tract. As proof of concept, the pH-responsive microcapsules were used to deliver tetracycline hydrochloride (TCH), used as a model therapeutic for intestinal infections, which can be translated to other drugs (e.g., capecitabine and tegafur–uracil). , …”

Section: Introductionmentioning

confidence: 99%

“…As proof of concept, the pH-responsive microcapsules were used to deliver tetracycline hydrochloride (TCH), used as a model therapeutic for intestinal infections, which can be translated to other drugs (e.g., capecitabine and tegafur−uracil). 21,22 2. EXPERIMENTAL SECTION 2.1.…”

Section: Introductionmentioning

confidence: 99%

In Situ Biofabrication of Microbial Cellulose Capsules Carrying Cubosomes: Toward Colon Targeted Multidrug Delivery

Ferreira,

Ezazi,

Otoni

et al. 2024

ACS Appl. Polym. Mater.

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The colon is a main absorption site (nutrients and drugs) and a target for oral therapeutic delivery. However, the latter is challenged by the fact that most drugs degrade during transit in the gastrointestinal tract (GIT). Herein, we rationally designed a universal controlled-release system based on cubosomes contained in microbial nanocellulose capsules that enabled oral administration and pH-triggered delivery of bioactives. We show that the bicontinuous cubosome structure allows the simultaneous incorporation of drugs with differing polarity or surface energy. Furthermore, the multidrug cubosomes combined with the cellulose carrier by in situ biofabrication was demonstrated as a route toward multicomponent 3D capsules with added protection in the GIT. The obtained capsules were subsequently coated with sodium alginate to enable responsiveness, achieving dual cargo-controlled release and site-specific administration. In sum, we successfully engineered pH-responsive, nontoxic microcapsules as a versatile platform for colon-targeted multidrug delivery.

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“…Although oral administration is accompanied with the highest patient compliance among the different routes of administration, only few chemotherapeutic drugs have been approved and used in the clinical practice, such as capecitabine (an orally administered prodrug of 5-FU, Xeloda) and tegafur-uracil. [2][3][4] This could be justified by the following limitations: i) poor stability of the drugs in the gastric conditions, ii) low bioavailability due to the first pass effect, and iii) the mucus barrier that prevents penetration and subsequent absorption of drugs. These factors have led to reductions in the therapeutic effects against colorectal cancer from oral formulation.…”

Section: Introductionmentioning

confidence: 99%

Microfluidized Dextran Microgels Loaded with Cisplatin/SPION Lipid Nanotherapeutics for Local Colon Cancer Treatment via Oral Administration

Liu

et al. 2022

Adv Healthcare Materials

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Multifunctional sequential targeted delivery system is developed as an efficient therapeutic strategy against malignant tumors with selective accumulation and minimal systemic drug absorption. The therapeutic system is comprised of microfluidized dextran microgels encapsulating cisplatin/superparamagnetic iron oxide nanoparticles (SPIONs)-loaded trilaurin-based lipid nanoparticles (LNPs). The microgel system is imparted hierarchically dual targeting via dextran and folic acid (FA) residues, leading to increases both in retention of the microgels in colon and in cellular uptake of the therapeutic LNPs by colon cancer cells while being used for oral therapeutic delivery. Encapsulation of the therapeutic LNPs into dextran microgels attained by microfluidized crosslinking reaction reduces gastrointestinal adhesion and prevents the FA-modified LNPs from cellular transport by proton-coupled FA transporters in small intestine during their oral delivery to colon. Upon enzymatic degradation of the dextran microgels by dextranase present exclusively in colon, LNPs thus released become more recognizable and readily internalized by FA receptor-overexpressing colon cancer cells. The combined chemo/magnetothermal therapeutic effect of dual targeted lipid nanoparticle-loaded microgels from entrapped lipidized cisplatin and alternating magnetic field-treated SPIONs significantly inhibits tumor growth and suppresses metastatic peritoneal carcinomatosis in orthotopic colon cancer-bearing mice.

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A Phase I Study of Irinotecan, Capecitabine (Xeloda), and Oxaliplatin in Patients With Advanced Colorectal Cancer

Abstract: The IXO regimen has a manageable toxicity profile with promising antitumor activity as first-line treatment of advanced and metastatic CRC.

Cited by 8 publications

References 29 publications

Capecitabine, Oxaliplatin, and Irinotecan (XELOXIRI) as Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Capecitabine, Oxaliplatin, and Irinotecan (XELOXIRI) as Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

In Situ Biofabrication of Microbial Cellulose Capsules Carrying Cubosomes: Toward Colon Targeted Multidrug Delivery

Microfluidized Dextran Microgels Loaded with Cisplatin/SPION Lipid Nanotherapeutics for Local Colon Cancer Treatment via Oral Administration

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