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[PMID]: 29331379
[Au] Autor:Shinagawa-Kobayashi Y; Kamimura K; Goto R; Ogawa K; Inoue R; Yokoo T; Sakai N; Nagoya T; Sakamaki A; Abe S; Sugitani S; Yanagi M; Fujisawa K; Nozawa Y; Koyama N; Nishina H; Furutani-Seiki M; Sakaida I; Terai S
[Ad] Address:Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
[Ti] Title:Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.
[So] Source:Biochem Biophys Res Commun;496(2):556-561, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. METHODS: The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. RESULTS: Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. CONCLUSION: We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow.
[Mh] MeSH terms primary: Antineoplastic Agents/adverse effects
Blood Flow Velocity/drug effects
Blood Vessels/drug effects
Blood Vessels/pathology
Histidine/pharmacology
Niacinamide/analogs & derivatives
Phenylurea Compounds/adverse effects
[Mh] MeSH terms secundary: Animals
Carcinoma, Hepatocellular/drug therapy
Humans
Liver Neoplasms/drug therapy
Niacinamide/adverse effects
Oryzias
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Antineoplastic Agents); 0 (Phenylurea Compounds); 25X51I8RD4 (Niacinamide); 4QD397987E (Histidine); 9ZOQ3TZI87 (sorafenib)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180115
[St] Status:MEDLINE

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[PMID]: 29447329
[Au] Autor:Martin M; Campone M; Bondarenko I; Sakaeva D; Krishnamurthy S; Roman L; Lebedeva L; Vedovato JC; Aapro M
[Ad] Address:Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
[Ti] Title:Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane.
[So] Source:Ann Oncol;, 2018 Feb 10.
[Is] ISSN:1569-8041
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Background: Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting, and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods: Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine (825 mg/m2 twice daily [bid], days 1-14) every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 bid, days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS. Results: Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone (hazard ratio 0.84, 95% confidence interval [CI] 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively). Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio 0.98, 95% CI 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%). Conclusions: Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic breast cancer. ClinicalTrials.gov: NCT01095003.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Cl] Clinical Trial:ClinicalTrial
[St] Status:Publisher
[do] DOI:10.1093/annonc/mdy063

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[PMID]: 29491111
[Au] Autor:Suenaga M; Akiyoshi T; Shinozaki E; Fujimoto Y; Matsusaka S; Konishi T; Nagayama S; Fukunaga Y; Kawakami K; Yokokawa T; Sugisaki T; Ueno M; Yamaguchi T
[Ad] Address:Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan m.suenaga1972@gmail.com.
[Ti] Title:A Feasibility Study of Capecitabine and Oxaliplatin for Patients with Stage II/III Colon Cancer -ACTOR Study.
[So] Source:Anticancer Res;38(3):1741-1747, 2018 03.
[Is] ISSN:1791-7530
[Cp] Country of publication:Greece
[La] Language:eng
[Ab] Abstract:BACKGROUND/AIM: Past studies have suggested that adjuvant capecitabine and oxaliplatin (CAPOX) provides decreased tumor relapse and longer survival in patients with curatively resected colon cancer. We report the first evidence of the feasibility of adjuvant CAPOX in Japanese patients with early colon cancer. PATIENTS AND METHODS: Eligible patients had histologically-confirmed stage II/III colon cancer and received curative resection. The primary endpoint was completion rate of treatment after 8 cycles of adjuvant CAPOX. RESULTS: Thirty-six patients were enrolled in this study. The completion rate of CAPOX and oxaliplatin were 77.8% and 61.1%, respectively. The incidence of grade ≥3 adverse events was neutropenia (n=6), thrombocytopenia (n=3), nausea (n=5), hand-foot syndrome (n=1) and peripheral sensory neuropathy (n=1). Three-year disease-free survival for stage II patients and stage III patients were 100% and 79.3%, respectively. CONCLUSION: Adjuvant CAPOX can be safely administered to Japanese patients with stage II/III colon cancer.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Process

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[PMID]: 29491097
[Au] Autor:Nervo A; Gallo M; Samà MT; Felicetti F; Alfano M; Migliore E; Marchisio F; Berardelli R; Arvat E; Piovesan A
[Ad] Address:Oncological Endocrinology Unit, Department of Medical Sciences, Città della Salute e della Scienza Hospital, Turin, Italy alice.nervo@gmail.com.
[Ti] Title:Lenvatinib in Advanced Radioiodine-refractory Thyroid Cancer: A Snapshot of Real-life Clinical Practice.
[So] Source:Anticancer Res;38(3):1643-1649, 2018 03.
[Is] ISSN:1791-7530
[Cp] Country of publication:Greece
[La] Language:eng
[Ab] Abstract:BACKGROUND: We retrospectively analyzed the efficacy and safety of lenvatinib in 12 patients with advanced radioiodine-refractory thyroid cancer in the setting of daily clinical practice. PATIENTS AND METHODS: The starting daily dose of lenvatinib was 24 mg, tapered in the case of adverse events. Disease status was periodically evaluated by a single radiologist and safety assessment was regularly performed. RESULTS: After a median follow-up of 13.3 months, 6- and 12-month progression-free survival rates were 63.6% and 54.6%, respectively. Overall survival at 6 and 12 months was 83.3% and 75.0%. Partial response was observed in five patients, while two showed stable disease as their best response. Conversely, progressive disease at first radiological assessment was detected in four patients. All patients experienced at least one adverse event, including systemic and gastrointestinal toxicity, high blood pressure and hand-foot syndrome. In order to manage toxicity, transient drug interruption and dose reduction were required in 10 and 9 cases, respectively. CONCLUSION: Our data confirm lenvatinib efficacy in patients with advanced thyroid cancer, despite an important toxic profile.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Process

  5 / 1585 MEDLINE  
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[PMID]: 29390380
[Au] Autor:Zhao C; Zhang Q; Qiao W
[Ad] Address:Department of Radiation Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
[Ti] Title:Significant efficacy and well safety of apatinib combined with radiotherapy in NSCLC: Case report.
[So] Source:Medicine (Baltimore);96(50):e9276, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:RATIONALE: The outcomes of locally advanced non-small cell lung cancer (NSCLC) remain poor, in particular, the frail elderly patients cannot tolerate chemotherapy. The new efficient, safe, and more specific treatments are needed. Radiation combined with targeted therapy is the focus of research in recent years. Apatinib is highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, studies have revealed that apatinib inhibit the growth of solid tumors including NSCLC. However, there is no report to evaluate its efficacy and safety in combined with radiotherapy for the advanced NSCLC. Our original research about to explore the use of apatinib combined with radiotherapy in treatment of NSCLC and its side effects are as follows. PATIENT CONCERNS: Patient 1, man, 78-year old, admitted to hospital, due to "thoracalgia and dyspnea for 1 month." Chest and abdomen computed tomography (CT) scan showed that there was a huge mass at the left upper lobe and multiple lymph nodes metastasis in mediastinum and left hilus pulmonis, the diagnosis was left lung squamous cell carcinoma, however, the mass was huge and age of patient was elder, post chemotherapy the mass were bigger and more severe. Patient 2, man, 61-year old, the diagnosis was squamous carcinoma on left upper lobe with right mediastinum lymph notes metastases recrudescence post chemoradiotherapy. DIAGNOSES: Case 1 was diagnosed left lung huge squamous cell carcinoma and case 2 was left lung squamous carcinoma, the primary lesion and right mediastinum lymph notes metastases recrudescence after radiochemotherapy. INTERVENTIONS: Both patients who received local radiation therapy and concurrent apatinib. Apatinib 250 mg once daily in combination with thoracic radiotherapy (2 Gy/d, 5 fractions/wk) followed by Apatinib Maintenance Therapy. OUTCOMES: Favorable oncologic outcomes were achieved in the 2 cases after the treatment. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of was controllable and tolerable, no dyspnea, no hemoptysis, no thoracalgia. LESSONS: Apatinib combined with thoracic radiotherapy, may be an option for recurring or advanced NSCLC. But that still warrants further investigation in the prospective study.
[Mh] MeSH terms primary: Antineoplastic Agents/therapeutic use
Carcinoma, Non-Small-Cell Lung/drug therapy
Carcinoma, Non-Small-Cell Lung/radiotherapy
Lung Neoplasms/drug therapy
Lung Neoplasms/radiotherapy
Pyridines/therapeutic use
[Mh] MeSH terms secundary: Aged
Combined Modality Therapy
Humans
Male
Middle Aged
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (Antineoplastic Agents); 0 (Pyridines); 5S371K6132 (apatinib)
[Em] Entry month:1802
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009276

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[PMID]: 29486916
[Au] Autor:Loree JM; Sha A; Soleimani M; Kennecke HF; Ho MY; Cheung WY; Mulder KE; Abadi S; Spratlin JL; Gill S
[Ad] Address:Division of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada.
[Ti] Title:Survival Impact of CAPOX Versus FOLFOX in the Adjuvant Treatment of Stage III Colon Cancer.
[So] Source:Clin Colorectal Cancer;, 2018 Feb 07.
[Is] ISSN:1938-0674
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Capecitabine and oxaliplatin (CAPOX) and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) are both used in the adjuvant treatment of colon cancer, and while their efficacy is assumed to be similar, they have not been directly compared. We reviewed the toxicity profiles, relative dose intensity (RDI), and survival associated with these regimens across a multi-institutional cohort. PATIENTS AND METHODS: We identified 394 consecutively treated patients with stage III colon cancer who received an oxaliplatin-containing regimen. RDI was defined as the total dose received divided by the intended total dose if all cycles were received. RESULTS: FOLFOX was associated with increased mucositis (6.2% vs. 0.7%, P = .0069) and neutropenia (25.9% vs. 8.6%, P < .0001), while CAPOX was associated with increased dose-limiting toxicities (DLTs) (90.7% vs. 80.2%, P = .0055), diarrhea (31.8% vs. 9.0%, P < .0001), and hand-foot syndrome (19.9% vs. 2.1%, P < .0001). Higher median RDI of fluoropyrimidine (93.7% vs. 80.0%, P < .0001) and oxaliplatin (87.2% vs. 76.3%, P < .0001) was noted for patients receiving FOLFOX. Reducing the duration from 6 to 3 months would have prevented 28.7% of FOLFOX and 20.5% of CAPOX patients from ever experiencing a DLT (P = .0008). Overall survival did not differ by regimen (hazard ratio = 0.73; 95% confidence interval 0.45-1.22; P = .24). However, CAPOX was associated with improved disease-free survival (3-year disease-free survival 83.8% vs. 73.4%, P = .022), which remained significant in high-risk (T4 or N2) (P = .039) but not low-risk patients (P = .19). CONCLUSION: CAPOX may be associated with improved disease-free survival despite greater toxicities and lower RDI. Reducing adjuvant chemotherapy duration to 3 months would prevent 26% of patients from ever experiencing a DLT.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180228
[Lr] Last revision date:180228
[St] Status:Publisher

  7 / 1585 MEDLINE  
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[PMID]: 29387963
[Au] Autor:Winther SB; Bjerregaard JK; Schonnemann KR; Ejlsmark MW; Krogh M; Jensen HA; Pfeiffer P
[Ad] Address:Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark. stine.winther@rsyd.dk.
[Ti] Title:S-1 (Teysuno) and gemcitabine in Caucasian patients with unresectable pancreatic adenocarcinoma.
[So] Source:Cancer Chemother Pharmacol;81(3):573-578, 2018 Mar.
[Is] ISSN:1432-0843
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:PURPOSE: Gemcitabine has been standard of care in advanced pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS-1); however, no data are published in Caucasian patients. We report the first study with a combination of GemS-1 in an unselected cohort of Caucasian PC patients. METHODS: In this observational cohort study, we analyzed efficacy and toxicity prospectively. RESULTS: From July 2012 to July 2014, 64 patients received at least one cycle of GemS-1. 16 patients started therapy with gemcitabine and capecitabine (GemCap) but switched to GemS-1 after median 3 cycles of GemCap due to toxicity (hand-foot syndrome). 48 patients received GemS-1 as initial therapy. For the complete cohort, median age was 68 years (range 44-80); 22 patients (34%) had locally advanced PC; 42 patients (66%) had metastatic disease. Five patients had received prior adjuvant therapy with gemcitabine and 9 pts had received prior first-line therapy. The most common adverse event was fatigue (86%), however, only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 8.1 (95% CI 6.9-9.0) months and median OS was 11.7 (95% CI 10.7-13.1) months in the whole GemS-1 population. In the 48 patients starting with GemS-1, median PFS was 7.7 (95% CI 6.7-8.9) months and median OS was 11.5 (95% CI 9.7-12.3) months. CONCLUSIONS: The combination of gemcitabine and S-1 is safe and associated with promising efficacy in a Caucasian population; however, this needs to be confirmed in prospective clinical trials.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180225
[Lr] Last revision date:180225
[St] Status:In-Data-Review
[do] DOI:10.1007/s00280-018-3528-5

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[PMID]: 29381963
[Au] Autor:Liang L; Wang L; Zhu P; Xia Y; Qiao Y; Hui K; Hu C; Ren Y; Jiang X
[Ad] Address:Department of Radiation Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University.
[Ti] Title:Apatinib concurrent gemcitabine for controlling malignant ascites in advanced pancreatic cancer patient: A case report.
[So] Source:Medicine (Baltimore);96(47):e8725, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:RATIONALE: Malignant ascites (MA) is one of the poor prognostic factors for advanced pancreatic cancer and can bring about serious symptoms. The improvement of quality of life for patients is priority. However, there is no standard method for the treatment for pancreatic cancer-mediated MA. Apatinib is a novel and highly selective tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. There are no reports of concurrent apatinib with gemcitabine in patients with pancreatic cancer-mediated MA. PATIENT CONCERNS: Herein, we presented a 64-year-old man patient who visited hospital due to abdominal pain for 1 month. DIAGNOSES: He was initially diagnosed with pancreatic cancer and his first symptom was MA. INTERVENTIONS: After failing in tube drainage and gemcitabine therapy, the patient received gemcitabine combined apatinib orally and after administrated 1 month, the MA was evaluated as nearly clear response according to the RECIST 1.1 standard, and without further need of paracentesis. The CEA and CA199 reached the lowest level after administrating for 2.5 months during the treatment process. OUTCOMES: 10.5 months following apatinib administration, the patient achieved a progression-free survival for more than 11 months. Hypertension (grade IV), hand-foot syndrome (grade I) and proteinuria (grade II) were observed. LESSONS: It indicated that apatinib concurrent gemcitabine may be a superior choice for pancreatic cancer-mediated MA. Further clinical trials required to confirm its efficacy and safety.
[Mh] MeSH terms primary: Antineoplastic Agents/therapeutic use
Ascites/drug therapy
Ascites/etiology
Deoxycytidine/analogs & derivatives
Pancreatic Neoplasms/complications
Pyridines/therapeutic use
[Mh] MeSH terms secundary: Antineoplastic Agents/administration & dosage
Deoxycytidine/administration & dosage
Deoxycytidine/therapeutic use
Drug Therapy, Combination
Humans
Male
Middle Aged
Protein-Tyrosine Kinases/antagonists & inhibitors
Pyridines/administration & dosage
Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (Antineoplastic Agents); 0 (Pyridines); 0W860991D6 (Deoxycytidine); 5S371K6132 (apatinib); B76N6SBZ8R (gemcitabine); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
[Em] Entry month:1802
[Cu] Class update date: 180220
[Lr] Last revision date:180220
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008725

  9 / 1585 MEDLINE  
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[PMID]: 29458237
[Au] Autor:Park IH; Im SA; Jung KH; Sohn JH; Park YH; Lee KS; Sim SH; Park KH; Kim JH; Nam BH; Kim HJ; Kim TY; Lee KH; Kim SB; Ahn JH; Lee S; Ro J
[Ad] Address:Division of Internal Medicine, Center for Breast Cancer, National Cancer Center, Goyang, Korea.
[Ti] Title:Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01).
[So] Source:Cancer Res Treat;, 2018 Feb 14.
[Is] ISSN:2005-9256
[Cp] Country of publication:Korea (South)
[La] Language:eng
[Ab] Abstract:Purpose: We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC). Materials and Methods: A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS. Results: There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea. Conclusion: Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180220
[Lr] Last revision date:180220
[St] Status:Publisher
[do] DOI:10.4143/crt.2017.562

  10 / 1585 MEDLINE  
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[PMID]: 29451302
[Au] Autor:Ter Veer E; Creemers A; de Waal L; van Oijen MGH; van Laarhoven HWM
[Ad] Address:Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
[Ti] Title:Comparing cytotoxic backbones for first-line trastuzumab-containing regimens in HER2-positive advanced esophagogastric cancer: A meta-analysis.
[So] Source:Int J Cancer;, 2018 Feb 16.
[Is] ISSN:1097-0215
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:According to the ToGA study, trastuzumab plus cisplatin and capecitabine/5-fluorouracil (5-FU) is standard first-line treatment for HER2-positive advanced esophagogastric cancer. We examined the relative efficacy and safety of alternative trastuzumab-based cytotoxic backbone regimens compared to the standard ToGA regimen using meta-analysis. We searched Medline, EMBASE, CENTRAL and ASCO and ESMO up to March 2017 for studies investigating alternative first-line trastuzumab-based regimens for HER2-positive esophagogastric cancer, defined as high protein expression IHC3+ or IHC2+ and gene amplification by in-situ-hybridisation. We compared primary outcome overall survival (OS) of alternative trastuzumab-based regimens to the ToGA regimen. Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated by extraction of the published Kaplan-Meier curves. Incidence counts and toxicity sample-sizes were extracted for adverse events and compared using single-arm proportion meta-analysis in R. Fifteen studies (N=557 patients) were included. OS was significantly longer with regimen trastuzumab plus doublet oxaliplatin and capecitabine/5-FU (median OS=20.7 months) versus ToGA (16.0 months, HR=0.75, 95%CI=0.59-0.99) and was less toxic. Trastuzumab plus doublet cisplatin and S-1 showed no OS difference versus ToGA, but showed a different toxicity profile, including less hand-foot syndrome. Trastuzumab plus cisplatin or capecitabine as singlet backbone showed significantly worse survival and more toxicity versus ToGA regimen. Trastuzumab with triplet cytotoxic backbones or with bevacizumab and doublet cytotoxic backbone showed no survival benefit and more toxicity. In conclusion, trastuzumab plus doublet cytotoxic backbone containing oxaliplatin is preferable over the ToGA regimen with cisplatin. S-1 can substitute capecitabine or 5-FU when specific toxicities are encountered. This article is protected by copyright. All rights reserved.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180216
[Lr] Last revision date:180216
[St] Status:Publisher
[do] DOI:10.1002/ijc.31325


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