Raltitrexed arterial infusion chemotherapy analysis

Chinese-German J Clin OncolOctober 2013, Vol. 12, No.10, P498- -P501|DOI 10.1007/s10330-013-1222-yRaltitrexed arterial infusion chemotherapy analysisJun Liang, Yuanlong Chen, Huijuan Pan, Ying Qian, Dan Xu, Min LiDepartment of Oncology, The People's Hospital of Wuxi Huishan Region, Wuxi 214187, ChinaReceived: 11 July 2013 1 Revised: 13 July 2013 1 Accepted: 25 September 2013⑥Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2013Abstract Objective: The aim of this study was to analysis raltitrexed by the safety and eficacy of intra-arterial infusionchemotherapy. Methods: Forty-seven cases in dfferent parts of cancer patients, interventional methods, based on digitalsubtraction angiography (DSA) prompt, raltitrexed-based chemotherapy, the tumor nourish artery infusion chemotherapy.Patients with postoperative chemotherapy side efects and complicaions, and eficacy assessments. Results: Forty-sevenpatients, 2 patients had I-I1 degree of bone marrow suppression, the rate was 4.26%, 34 cases of | to II degree gastroin-testinal reactions, 1 case of grade II gastrontestinal reations, the incidence of 2.13%, and 1 case mild diarhea. | degreesor more chemotherapy-related adverse reactions did not occur in this group of patients. AlI patients received at least 2 timesarterial infusion chemotherapy, complete remission (CR) 3 cases, partial remission (PR) 11 cases, stable disease (SD) 17cases, disease progression (PD) 6 cases, total effective rate of treatment 87.23%. Conclusion: Raltitrexed for intra-arterialchemotherapy is safe and efctive. However, due to the small number of this group of patients, time is short, its safety, ef-ficacy and long-term eficacy needs further observation and validation.Key words ralitrexed; transcatheter arterial chemo-infusion; security: validityRaltitrexed to thymine synthetase inhibitor, is quinaz- Treatmentoline folate analogs, are cytotoxic drugs, primarily for theSeldinger technique, took the right or left femoral ar-treatment of colorectal cancer. According to foreign liter- tery at the groin puncture site, local skin disinfection, lo-ature, raltitrexed has also been used in clinical treatmentcal anesthesia into the femoral artery puncture 5F catheterof gastric cancer, pancreatic cancer, esophageal cancer，sheath, used 4F or 5F catheter, the catheter was insertedhead and neck cancer and malignant pleural mesothe- into the tumor selectively nourish blood vessels, lunglioma, etc "。Raltitrexed arterial infusion chemotherapy chose bronchial artery (Fig. 1 and 2), esophageal cancerand abroad rarely reported, in July 2012 we have 2013 esophageal branches selected bronchial artery, esophagusin June in 47 patients with malignant tumors, the use of artery and left gastric artery, left gastric artery and gastricraltitrexed arterial infusion chemotherapy, the patient selected gastroduodenal artery, superior mesenteric ar-tolerated, and achieved satisfactory results.tery and rectal selected iliac artery, left hepatic carcinomachoice artery, internal thoracic artery and breast selectedMaterials and methodslateral thoracic artery. After successful intubation non-ionic contrast agent (Ioversol) 8-15 mL, with 3-6 mL/sStudyspeed injection line target arterial digital subtraction an-Forty-seven patients in 32 males and 15 females, aged giography (DSA). The tumor vascular supply and dyeing,47 to 81 years, mean age 58 years. Lung cancer 18 cases,and to observe whether the dangerous branch vessels,esophageal cancer 10 cases, gastric cancer 3 cases, rec- arteriovenous fistula, bleeding. For dangerous branchtal cancer 3 cases, liver cancer 11 cases, breast cancer 2 (intercostal arteries, spinal artery) and arterial tortuositycases. All patients were pathologically confirmed as ma- wallk the line of cases, the use of ultra 3F microcatheterlignant. TNM stage III - IV period. KPS scores 60 to 90 inserted into the target vessel selection, tried to avoid themin. Preoperative WBC > 4.5 x 10%/L, hemoglobin> 100 risk of arterial branches and normal tsse, reducing theg/L, platelets> 97 x 10%/L, albumin > 32 g/L, liver and incidence of complications and normal tssuse damage. Af-kidney function, electrolytes, coagulation, electrocardio- ter the tumor target vessel, slowly injected through thegram was normal.catheter diluted anticancer drugs (Table 1).Breast perfusion| 中国煤化工1 arm tour-Correspondence to: Liang Jun. Email: doctorliangjun@163.comniquet release everYHCNMH(ease the lo-cal concentration dGherfusion inChinese- German J Clin Oncol, October 2013, Vol. 12, No.10499Table 1 Regimen and doseCategoryPrograms and doseLung cancer, colorectal cancerRalitrexed 3 mg + nedaplatin 60 -80 mg + mitomycin 10 mgEsophageal cancer, gastric cancer, liver cancerRalitrexed 3 mg + nedaplatin 50- 80 mg + epirubicin 50 mgBreast CancerRaltitrexed 3 mg + cyclophosphamide 600 mg + epirubicin 50 mgFig. 1 Right bronchial arteriography showed: right hilar tumor staining Fig. 2 Left bronchial arteriography showed: left lung tumor staininglesionswith foreign stovepatients with hepatocellular carcinoma using epirubicin Effectiveness20 mg + 10 mL suspension lipiodol embolization. Afterthe puncture site to be elastic bandage bandaged puncture arterial infusion chemotherapy, followed up its efficacy,side limb braking 8 h, observed whether the puncturecomplete remission (CR) 3 cases, partial remission (PR)site bleeding, hematoma, and dorsalis pedis artery pulse,21 cases, stable disease (SD) 17 cases, disease progressionpostoperative fluid volume maintained at 1500-2000 mL, (PD) 6 cases, the total effective rate of treatment 87 .23%.such as conventional antiemetic prophylaxis side effects .Three cases of PD patients as esophageal cancer, liverof chemotherapy drugs. 3, 7 days, respectively, after the cancer, colorectal cancer and 1 case were lung metasta-first review of blood 1, 7 days review kidney function 1.sis or lung metastases increased, increases. Another four28 to 42 days after the first repeat the treatment.patients because of financial difficulties after two timesto give up treatment after intra-arterial infusion chemo-Resultstherapy.SecurityDiscussionAfter review of 47 patients and follow-up in twocases arise II III myelosuppression, the rate was 4.26%,Raltitrexed is highly selective antimetabolite drugs, aexpressed as leukopenia to 1.3- -2.3 x 109/L, platelets de- new generation of water-soluble inhibitor of thymidylatecreased to 39- 52 x 109/L, using recombinant human gran-synthase, as quinazoline folate analogue, active uptake byulocyte colony stimulating factor and recombinant hu- cells in the body soon after folic acid polyethylene gluta-man interleukin-11, the review back to normal. 34 cases myl acid synthase is metabolized to a series of poly -glu-occurred I-II degrees gastrointestinal reactions, nausea tamic acid compounds, these metabolites than raltitrexedand vomiting, temporary, after 2 to 3 days to relieve it- have a stronger role in resisting thymidylate synthase,self. 1 patient had grade II gastrointestinal reactions, the thereby inhibiting DNA synthesis, retention and can playrate was 2.13%, the enhanced antiemetic, added electro- a cell in the cell for a long time cytotoxicity 231. Currently,lytes, fluids and other symptomatic treatment four days patients carried out raltitrexed treatment of a variety ofgradually ease. One case of mild diarrhea, eliminate in- solid tumors, such as advanced colorectal cancer, malig-testinal infection, after adjusting the diet after diarrhea nant pleural mesot| 中国煤化工r，head andstops. Other I degrees of chemotherapy related adverse neck cancer, partic二ment of ad-reactions in this group of patients did not appear.vanced colorectalYHCNM H Gal mesothe-500www springerlink.com/content/1613 9089lioma tumors, a significant effect, better tolerated [4.case of mild diarrhea. Other I degrees of chemotherapy-Arterial infusion chemotherapy surgery is the use of related adverse reactions in this group of patients did notintervention methods, the catheter through the blood appear. Indicating that patients tolerated the treatmentvessels reach the tumor feeding artery, injecting drug well. After followed up, CR1 patients, PR11 cases, SD17treatment methods. The advantages are: (1) improve local cases, PD3 cases, the treatment, the total effective ratetumor drug concentration (dose intravenous drug use is was 87 .26%, indicating efficacy in this group of patientsthe same multiple of) directly kill tumor cells; (2) through is satisfied.the blood circulation through the body organs, played the Arterial infusion chemotherapy on local tumor con-role of intravenous chemotherapy; (3) reduce the maxi- trol rate is better, but the body is inferior to intravenousmum concentration and the concentration of blood-areachemotherapy. "Down period" was the main purpose ofunder the curve, reduce systemic adverse reactions. Most neoadjuvant chemotherapy in one, but the clinical ob-anti- cancer drugs within a certain range of its killing ef- servation that after chemotherapy, even down period forfect was concentration- dependent, the local concentra- the early, the prognosis is also a far cry from the real earlytion of doubling the number of cells increased killing cancer, how to improve the efficacy of chemotherapy inabout 10 times (51. Arterial infusion chemotherapy has ob- clinical research is always a major target [8]. Ishihara etvious advantages in this regard. At present, the technol- a19), the EAP program improvement, through differentogy has been widely used in various parts of the body the routes of administration arteriovenous full pharmacolog-treatment of tumors [6ical effects of various drugs, the treatment of advancedKhouri et al7] reported there are only 17 cases of liver gastric cancer with satisfactory results.metastases in patients with refractory colorectal cancer,Although intra-arterial chemotherapy relative to in-for at least two cycles of systemic chemotherapy (includ- travenous chemotherapy side effects and patient toler-ing oxaliplatin, irinotecan, fluorouracil, etc.) after a failed ance are better, but in patients with advanced cancer, nu-joint line raltitrexed oxaliplatin hepatic arterial infusion trition support therapy can not only improve the qualitychemotherapy, the results show progress before the me- of life in patients with advanced cancer, but you can cre-dian survival time was 10.5 months, the median survival ate an effective anti-tumor therapy opportunity, but alsotime after progression was 27.5 months. Toxicities includ- the comprehensive treatment of cancer is one importanting III -IV degrees leukopenia (17%) and thrombocytope- means (101.nia (17%), II degree of abdominal pain (47%). Therefore，The main purpose of this study was to find more ef-the first- line treatment failure, patients with isolated liver fective for arterial infusion chemotherapy drugs, ralti-metastases of colorectal cancer, raltitrexed and oxalipla- trexed as a specific inhibitor of thymidylate synthase, intin is feasible. This report shows raltitrexed hepaticpreclinical and clinical studies demonstrated significantrial infusion chemotherapy is safe, effective treatment of anti- tumor activity 11, preliminary analysis raltitrexedcolorectal liver metastases sure. But for other malignan- for arterial infusion chemotherapy is safe and effective.cies arterial infusion chemotherapy rarely reported.However, due to small number of cases in this group,Raltitrexed is a direct and specific thymidylate syn- time is short, its safety and efficacy of a large sample ofthase (TS) inhibitor, TS is thymidine triphosphate (TTP) cases also need to be explored further, long term effectsa key enzyme in the synthesis process, and TTP is nuclear need further observation verified. In addition, dependingDNA synthesis must nucleotide, inhibiting TS can cause on the pharmacological effects of chemotherapy drugs, .DNA breaks and apoptosis. Raltitrexed ingested by cells exploring a more rational and effective chemotherapywere reduced folate carrier leaves acyl polyglutamate regimens and routes of administration will be the direc-synthetase into polyglutamate forms of storage cells, play tion of our efforts. With the further advance of clinicala stronger TS inhibition. Raltitrexed polyglutamate TSin- trials, there will be more new programs for clinical, sohibition by enhancing the ability to extend the suppres- cancer patients to relieve pain and prolong life, improvesion time and improve its anti-tumor activity. Raltitrexed quality of life for maximum clinical benefit.administered intravenously after dilution takes only 15min. According raltitrexed pharmacological effects and Referencesusage characteristics, we believe that raltitrexed arterialinfusion treatment of various solid tumors is feasible.1. Planting A, De Jong M, Jansen P, et al. Phase | study of concomitantForty-seven patients received at least two times by in-chemoradiation with Rltitrexed in locally advanced head and necktra-arterial infusion chemotherapy, two cases arise II- IIIcancer. Eur J Cancer, 2005, 41: 93-97.myelosupression, the rate was 4.26%, 34 cases occurred 2. Jarmula A. Atilte inibitorts of tyidyate synthase as anicancerdrugs. 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