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article_id
string | article_words
sequence | article_bboxes
sequence | article_norm_bboxes
sequence | abstract
string | article_pdf_url
string |
---|---|---|---|---|---|
PMC3770628 | [
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"Dovepress",
"open",
"access",
"to",
"scientific",
"and",
"medical",
"research",
"O",
"ri",
"g",
"i",
"n",
"al",
"R",
"esearch",
"Open",
"Access",
"Full",
"Text",
"Article",
"Intravenous",
"iron",
"monotherapy",
"for",
"the",
"treatment",
"of",
"non-iron-deficiency",
"anemia",
"in",
"cancer",
"patients",
"undergoing",
"chemotherapy:",
"a",
"pilot",
"study",
"This",
"article",
"was",
"published",
"in",
"the",
"following",
"Dove",
"Press",
"journal:",
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"29",
"August",
"2013",
"Number",
"of",
"times",
"this",
"article",
"has",
"been",
"viewed",
"Hikmat",
"Abdel-Razeq",
"1",
"Salah",
"Abbasi",
"1",
"Iyad",
"Saadi",
"1",
"Rana",
"Jaber",
"2",
"Hazem",
"Abdelelah",
"1",
"Department",
"of",
"Internal",
"Medicine,",
"Department",
"of",
"Pharmacy,",
"King",
"Hussein",
"Cancer",
"Center,",
"Amman,",
"Jordan",
"1",
"2",
"of",
"patients",
"and",
"may",
"have",
"a",
"negative",
"effect",
"on",
"overall",
"survival.",
"Aims:",
"To",
"assess",
"the",
"efficacy",
"and",
"feasibility",
"of",
"intravenous",
"iron",
"therapy",
"in",
"patients",
"with",
"cancer",
"who",
"have",
"non-iron-deficiency",
"anemia",
"and",
"who",
"are",
"undergoing",
"treatment",
"with",
"chemotherapy",
"without",
"the",
"use",
"of",
"erythropoiesis-stimulating",
"agents.",
"Methods:",
"Adult",
"patients",
"with",
"solid",
"cancers",
"and",
"non-iron-deficiency",
"anemia",
"were",
"included.",
"Ferric",
"sucrose",
"at",
"a",
"dose",
"of",
"200",
"mg",
"was",
"given",
"in",
"short",
"intravenous",
"infusions",
"weekly",
"for",
"a",
"total",
"of",
"12",
"weeks.",
"Hemoglobin",
"level",
"was",
"measured",
"at",
"baseline,",
"every",
"3",
"weeks,",
"and",
"2",
"weeks",
"after",
"the",
"last",
"iron",
"infusion",
"(week",
"14).",
"Adverse",
"events",
"related",
"to",
"intravenous",
"iron",
"were",
"prospectively",
"reported.",
"Results:",
"Of",
"25",
"patients",
"included,",
"19",
"(76.0%)",
"completed",
"at",
"least",
"three",
"iron",
"infusions",
"and",
"14",
"(56.0%)",
"finished",
"the",
"planned",
"12",
"weeks",
"of",
"therapy.",
"The",
"mean",
"hemoglobin",
"level",
"of",
"the",
"25",
"patients",
"at",
"baseline",
"was",
"9.6",
"g/dL",
"(median,",
"9.9",
"g/dL;",
"range,",
"6.9",
"g/dL10.9",
"g/dL).",
"The",
"mean",
"change",
"in",
"hemoglobin",
"level",
"for",
"the",
"15",
"patients",
"who",
"completed",
"at",
"least",
"9",
"treatments",
"was",
"1.7",
"g/dL",
"(median,",
"1.1",
"g/dL;",
"range,",
"−1.9",
"g/dL",
"to",
"3.2",
"g/dL);",
"it",
"reached",
"2.1",
"g/dL",
"(median,",
"1.3",
"g/dL;",
"range,",
"−0.2",
"g/dL",
"to",
"4.6",
"g/dL;",
"P",
"=",
"0.0007)",
"for",
"the",
"14",
"patients",
"who",
"completed",
"all",
"12",
"weekly",
"treatments.",
"Five",
"(20.0%)",
"patients",
"were",
"transfused",
"and",
"considered",
"as",
"treatment",
"failures.",
"No",
"treatment-related",
"adverse",
"events",
"were",
"reported.",
"Conclusion:",
"Intravenous",
"iron",
"treatment",
"alone",
"is",
"safe",
"and",
"may",
"reduce",
"blood",
"transfusion",
"require-",
"ments",
"and",
"improve",
"hemoglobin",
"level",
"in",
"patients",
"with",
"cancer",
"who",
"are",
"undergoing",
"anticancer",
"therapy.",
"Further",
"randomized",
"studies",
"are",
"needed",
"to",
"confirm",
"these",
"findings.",
"Keywords:",
"anemia,",
"cancer,",
"chemotherapy,",
"intravenous",
"iron,",
"transfusion",
"Introduction",
"Correspondence:",
"Hikmat",
"Abdel-Razeq",
"Department",
"of",
"Internal",
"Medicine,",
"Section",
"of",
"Hematology",
"and",
"Medical",
"Oncology,",
"King",
"Hussein",
"Cancer",
"Center,",
"Amman",
"11194,",
"Jordan",
"Tel",
"+962",
"6",
"530",
"0460",
"Email",
"habdelrazeq@khcc.jo",
"submit",
"your",
"manuscript",
"|",
"www.dovepress.com",
"Dovepress",
"http://dx.doi.org/10.2147/DDDT.S45674",
"Anemia",
"is",
"a",
"common",
"complication",
"of",
"cancer",
"and",
"its",
"treatment.",
"It",
"occurs",
"in",
"more",
"than",
"50%",
"of",
"patients",
"and",
"may",
"reach",
"90%",
"in",
"certain",
"types",
"of",
"cancers,",
"especially",
"in",
"patients",
"undergoing",
"chemotherapy",
"and/or",
"radiation",
"therapy.",
"1",
"Anemia",
"is",
"defined",
"as",
"an",
"inadequate",
"circulating",
"level",
"of",
"hemoglobin",
"(Hb)",
"(Hb",
",12",
"g/dL)",
"and",
"may",
"arise",
"as",
"a",
"result",
"of",
"the",
"underlying",
"disease,",
"bleeding,",
"poor",
"nutrition,",
"chemotherapy,",
"or",
"radiation",
"therapy.",
"Preliminary",
"studies",
"suggest",
"that",
"survival",
"and",
"loco-regional",
"control",
"after",
"radiation",
"therapy,",
"especially",
"in",
"head",
"and",
"neck",
"cancers,",
"may",
"be",
"compromised",
"by",
"anemia.",
"2–4",
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"2013:7",
"939–944",
"939",
"©",
"2013",
"Abdel-Razeq",
"et",
"al,",
"publisher",
"and",
"licensee",
"Dove",
"Medical",
"Press",
"Ltd.",
"This",
"is",
"an",
"Open",
"Access",
"article",
"which",
"permits",
"unrestricted",
"noncommercial",
"use,",
"provided",
"the",
"original",
"work",
"is",
"properly",
"cited.",
"Dovepress",
"Abdel-Razeq",
"et",
"al",
"Anemia",
"often",
"worsens",
"symptoms",
"such",
"as",
"fatigue,",
"weakness,",
"and",
"dyspnea,",
"and",
"thus",
"may",
"have",
"a",
"negative",
"effect",
"on",
"quality",
"of",
"life",
"(QOL)",
"and",
"performance",
"status",
"in",
"patients",
"with",
"cancer.",
"Thus,",
"to",
"improve",
"physical",
"functioning,",
"QOL,",
"and",
"prognosis",
"in",
"patients",
"with",
"cancer,",
"it",
"would",
"be",
"reasonable",
"to",
"take",
"a",
"proactive",
"approach",
"in",
"identifying",
"populations",
"who",
"need",
"treatment",
"for",
"cancer-associated",
"anemia",
"(CAA)",
"and",
"provide",
"timely",
"management.",
"Blood",
"transfusion",
"is",
"an",
"effective",
"way",
"to",
"replace",
"depleted",
"Hb",
"within",
"a",
"short",
"period,",
"but",
"the",
"effect",
"is,",
"unfortunately,",
"temporary",
"and",
"can",
"cause",
"serious",
"adverse",
"risks",
"and",
"increased",
"mortality.",
"In",
"randomized",
"clinical",
"trials",
"in",
"patients",
"with",
"CAA,",
"erythropoiesis-stimulating",
"agents",
"(ESAs)",
"produced",
"significant",
"increases",
"in",
"Hb",
"level,",
"decreased",
"transfusion",
"requirements,",
"and",
"improved",
"QOL.",
"5–7",
"However,",
"30%–50%",
"of",
"patients",
"do",
"not",
"respond",
"to",
"such",
"agents.",
"In",
"addition,",
"the",
"use",
"of",
"ESAs",
"often",
"causes",
"concern",
"about",
"severe",
"adverse",
"reactions.",
"6,8",
"In",
"several",
"studies,",
"ESAs",
"were",
"found",
"to",
"shorten",
"overall",
"survival",
"time,",
"or",
"time",
"to",
"tumor",
"progression",
"in",
"patients",
"whose",
"Hb",
"level",
"reached",
"more",
"than",
"12",
"g/dL.",
"These",
"studies",
"included",
"patients",
"with",
"different",
"primary",
"cancers,",
"such",
"as",
"breast,",
"lung,",
"head",
"and",
"neck,",
"cervix,",
"and",
"lymphomas.",
"9–11",
"The",
"lack",
"of",
"response",
"to",
"erythropoietin",
"stimulation",
"in",
"patients",
"with",
"cancer",
"is",
"partly",
"attributed",
"to",
"the",
"functional",
"iron",
"defi-",
"ciency",
"state,",
"in",
"which",
"the",
"high",
"rate",
"of",
"erythropoiesis",
"exceeds",
"the",
"delivery",
"of",
"usable",
"iron,",
"despite",
"adequate",
"iron",
"stores.",
"12",
"Absolute",
"iron",
"deficiency,",
"in",
"contrast,",
"occurs",
"when",
"iron",
"delivery",
"is",
"impaired",
"because",
"iron",
"stores",
"are",
"depleted",
"(serum",
"ferritin,",
",100",
"ng/mL;",
"transferring",
"saturation,",
",20%).",
"13",
"Hepcidin,",
"a",
"peptide",
"hormone",
"produced",
"by",
"the",
"liver,",
"is",
"up-",
"regulated",
"in",
"chronic",
"inflammatory",
"states",
"including",
"cancer.",
"Hepcidin",
"inhibits",
"iron",
"transport",
"across",
"cell",
"membranes,",
"thus",
"decreasing",
"the",
"accessibility",
"of",
"stored",
"iron",
"and",
"gastro-",
"intestinal",
"absorption",
"of",
"dietary",
"iron,",
"leading",
"to",
"an",
"increased",
"frequency",
"of",
"iron-restricted",
"erythropoiesis.",
"14–16",
"Many",
"randomized",
"trials",
"examined",
"the",
"role",
"of",
"intravenous",
"(IV)",
"iron",
"in",
"addition",
"to",
"ESAs",
"in",
"the",
"treatment",
"of",
"anemia",
"in",
"patients",
"with",
"cancer.",
"Many",
"of",
"these",
"studies",
"showed",
"improve-",
"ment",
"in",
"ESA",
"response,",
"time",
"to",
"maximal",
"response,",
"reduction",
"in",
"ESA",
"dose,",
"and",
"improvement",
"in",
"QOL",
"parameters",
"(when",
"measured)",
"in",
"favor",
"of",
"the",
"combination",
"over",
"ESAs",
"alone.",
"The",
"observed",
"benefit",
"was",
"independent",
"of",
"baseline",
"iron",
"parameters.",
"17–21",
"One",
"study",
"found",
"a",
"36%",
"reduction",
"in",
"the",
"number",
"of",
"patients",
"transfused.",
"21",
"This",
"pilot",
"study",
"assessed",
"the",
"efficacy",
"and",
"feasibility",
"of",
"IV",
"iron",
"monotherapy",
"in",
"patients",
"with",
"cancer",
"who",
"have",
"anemia",
"and",
"who",
"are",
"undergoing",
"treatment",
"with",
"chemotherapy",
"and/or",
"radiation",
"therapy",
"without",
"the",
"use",
"of",
"ESAs.",
"940",
"submit",
"your",
"manuscript",
"|",
"www.dovepress.com",
"Dovepress",
"Patients",
"and",
"methods",
"Study",
"design",
"Patients",
"received",
"the",
"study",
"treatment",
"for",
"12",
"weeks",
"followed",
"by",
"a",
"4-week",
"follow-up",
"period.",
"Eligible",
"patients",
"were",
"at",
"least",
"18",
"years",
"old,",
"about",
"to",
"start",
"a",
"cycle",
"of",
"chemotherapy",
"and/or",
"radiation",
"therapy",
"within",
"1",
"week",
"of",
"inclusion,",
"and",
"had",
"a",
"nonmyeloid",
"malignancy,",
"Hb",
"levels",
"of",
"11.0",
"g/dL",
"or",
"less,",
"a",
"life",
"expectancy",
"of",
"more",
"than",
"24",
"weeks,",
"and",
"an",
"Eastern",
"Cooperative",
"Oncology",
"Group",
"performance",
"status",
"of",
"0–2.",
"Patients",
"were",
"also",
"required",
"to",
"have",
"a",
"serum",
"ferritin",
"level",
"of",
"100",
"ng/mL",
"or",
"higher",
"or",
"transferrin",
"saturation",
"(TSAT)",
"levels",
"of",
"15%",
"or",
"higher",
"and",
"to",
"have",
"received",
"no",
"ESAs",
"or",
"IV",
"iron",
"therapy",
"within",
"30",
"days",
"and",
"no",
"oral",
"iron",
"therapy",
"(27",
"mg/day",
"or",
"more)",
"within",
"7",
"days",
"before",
"enrollment.",
"Patients",
"were",
"excluded",
"for",
"leukoerythroblastic",
"features",
"on",
"blood",
"film,",
"hemolysis,",
"gastrointestinal",
"bleeding,",
"folate",
"or",
"vitamin",
"B12",
"deficiency,",
"elevated",
"serum",
"ferritin",
"($900",
"ng/mL)",
"or",
"transferrin",
"saturation",
"(TSAT)",
"($35%)",
"levels,",
"pregnancy",
"or",
"lactation,",
"liver",
"dysfunction",
"(grade",
"2",
"or",
"higher",
"based",
"on",
"National",
"Cancer",
"Institute",
"Common",
"Toxicity",
"Criteria),",
"renal",
"dysfunction",
"(serum",
"creatinine",
"levels",
"$2.0",
"mg/dL),",
"active",
"infection",
"requiring",
"systemic",
"antibiotics,",
"personal",
"or",
"fam-",
"ily",
"history",
"of",
"hemochromatosis,",
"comorbidities",
"precluding",
"study",
"participation,",
"hypersensitivity",
"to",
"IV",
"iron,",
"red",
"blood",
"cell",
"transfusion",
"within",
"the",
"last",
"2",
"weeks,",
"or",
"any",
"investiga-",
"tional",
"agent",
"within",
"30",
"days",
"before",
"enrollment.",
"Patients",
"were",
"not",
"allowed",
"to",
"take",
"any",
"vitamin,",
"mineral,",
"or",
"herbal",
"supplements",
"containing",
"27",
"mg",
"or",
"more",
"of",
"iron",
"per",
"day",
"or",
"100",
"mg",
"vitamin",
"C",
"per",
"day",
"during",
"the",
"study",
"or",
"follow-up",
"period.",
"Blood",
"transfusions",
"were",
"permitted",
"at",
"the",
"primary",
"physician's",
"discretion",
"if",
"Hb",
"levels",
"decreased",
"to",
"8",
"g/dL",
"or",
"less,",
"and",
"such",
"patients",
"were",
"considered",
"treatment",
"failures.",
"Changes",
"to",
"the",
"chemotherapy",
"plan",
"were",
"permitted.",
"Written",
"informed",
"consent",
"was",
"provided",
"by",
"all",
"patients",
"before",
"study",
"participation,",
"and",
"the",
"protocol",
"and",
"supporting",
"docu-",
"ments",
"were",
"approved",
"by",
"the",
"institutional",
"review",
"board",
"of",
"King",
"Hussein",
"Cancer",
"Center.",
"The",
"study",
"was",
"conducted",
"in",
"accordance",
"with",
"the",
"Declaration",
"of",
"Helsinki",
"and",
"Good",
"Clinical",
"Practice",
"as",
"contained",
"in",
"the",
"US",
"Code",
"of",
"Federal",
"Regulations",
"that",
"governs",
"the",
"protection",
"of",
"human",
"subjects",
"and",
"the",
"obligations",
"of",
"clinical",
"investigators.",
"Treatment",
"Patients",
"received",
"200",
"mg",
"ferric",
"hydroxide",
"sucrose",
"diluted",
"in",
"100",
"mL",
"normal",
"saline",
"and",
"infused",
"over",
"the",
"course",
"of",
"1",
"hour",
"weekly",
"for",
"a",
"total",
"of",
"12",
"weeks.",
"The",
"first",
"dose",
"was",
"given",
"during",
"the",
"first",
"clinic",
"visit",
"(±4",
"days",
"from",
"the",
"initiation",
"of",
"chemotherapy",
"or",
"radiation",
"therapy).",
"TSAT",
"was",
"monitored,",
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"2013:7",
"Dovepress",
"as",
"protocol",
"mandated",
"withholding",
"iron",
"therapy",
"when",
"TSAT",
"levels",
"were",
"higher",
"than",
"50%.",
"Assessment",
"At",
"the",
"first",
"clinic",
"visit",
"(week",
"1;",
"baseline),",
"a",
"blood",
"sample",
"was",
"obtained",
"for",
"laboratory",
"assessments",
"before",
"the",
"study",
"treat-",
"ment",
"was",
"started.",
"Patients",
"attended",
"weekly",
"clinic",
"visits",
"for",
"treatment",
"and",
"assessment;",
"and",
"returned",
"for",
"follow-up",
"visits",
"at",
"week",
"14",
"which",
"included",
"a",
"complete",
"physical",
"examination.",
"Complete",
"blood",
"count",
"and",
"TSAT",
"were",
"done",
"every",
"3",
"weeks,",
"and",
"again",
"2",
"weeks",
"after",
"last",
"treatment",
"(week",
"14).",
"Complete",
"laboratory",
"assessment",
"(Hb,",
"serum",
"ferritin,",
"reticulocyte",
"count,",
"transferrin,",
"TSAT,",
"serum",
"iron,",
"total",
"iron",
"binding",
"capacity,",
"red",
"cell",
"indices,",
"white",
"blood",
"cell",
"count",
"with",
"differential,",
"platelet",
"count,",
"and",
"serum",
"chemistries)",
"were",
"done",
"at",
"week",
"1",
"and",
"at",
"week",
"14",
"(end",
"of",
"study).",
"Adverse",
"events",
"were",
"assessed",
"at",
"each",
"clinic",
"visit",
"until",
"study",
"completion",
"or",
"withdrawal,",
"and",
"during",
"the",
"30",
"days",
"after",
"the",
"last",
"study",
"treatment.",
"Statistical",
"analysis",
"Hb",
"test",
"results",
"were",
"presented",
"as",
"mean,",
"median,",
"and",
"range",
"through",
"all",
"12",
"weeks.",
"The",
"same",
"was",
"done",
"to",
"show",
"the",
"changes",
"of",
"Hb",
"level",
"every",
"3",
"weeks.",
"Comparison",
"between",
"means",
"of",
"Hb",
"level",
"were",
"made",
"between",
"the",
"baseline",
"Hb",
"and",
"Hb",
"levels",
"in",
"the",
"following",
"weeks,",
"using",
"t-test.",
"A",
"significance",
"criterion",
"of",
"P",
",",
"0.05",
"was",
"used",
"in",
"the",
"analysis.",
"All",
"analyses",
"were",
"performed",
"using",
"SAS",
"version",
"9.1",
"(SAS",
"Institute",
"Inc,",
"Cary,",
"NC,",
"USA).",
"Intravenous",
"iron",
"therapy",
"for",
"cancer-associated",
"anemia",
"Table",
"1",
"Characteristics",
"of",
"the",
"25",
"patients",
"with",
"cancer",
"who",
"received",
"intravenous",
"iron",
"therapy",
"for",
"non-iron-deficiency",
"anemia",
"Patient",
"Sex",
"Age,",
"years",
"Type",
"of",
"cancer",
"Treatment",
"1",
"2",
"3",
"4",
"5",
"Male",
"Female",
"Female",
"Female",
"Female",
"65",
"48",
"50",
"41",
"72",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"6",
"7",
"8",
"9",
"10",
"Female",
"Male",
"Male",
"Female",
"Female",
"57",
"71",
"62",
"67",
"70",
"11",
"12",
"13",
"14",
"Female",
"Male",
"Male",
"Female",
"50",
"56",
"77",
"27",
"15",
"16",
"17",
"18",
"Female",
"Female",
"Female",
"Male",
"33",
"61",
"44",
"54",
"Hodgkin's",
"lymphoma",
"Neuroblastoma",
"Breast",
"cancer",
"High",
"grade",
"sarcoma",
"Non-small",
"cell",
"lung",
"cancer",
"Breast",
"cancer",
"Prostate",
"cancer",
"Leg",
"leiomyosarcoma",
"Breast",
"cancer",
"Endometrial",
"adenocarcinoma",
"Uterine",
"sarcoma",
"Bladder",
"cancer",
"Colon",
"cancer",
"Neuroendocrine",
"tumor",
"Osteosarcoma",
"Breast",
"cancer",
"Ewing",
"sarcoma",
"Renal",
"cell",
"carcinoma",
"19",
"Female",
"66",
"20",
"21",
"22",
"Female",
"Female",
"Male",
"55",
"53",
"66",
"23",
"24",
"Female",
"Male",
"69",
"51",
"25",
"Female",
"31",
"Uterine",
"leiomyosarcoma",
"Breast",
"cancer",
"Gastric",
"cancer",
"Rectal",
"cancer",
"Breast",
"cancer",
"Desmoplastic",
"round",
"cell",
"Breast",
"cancer",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Sunitinib",
"and",
"radiotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"and",
"radiotherapy",
"Chemotherapy",
"Chemotherapy",
"Chemotherapy",
"Results",
"Twenty-five",
"patients",
"(17",
"women",
"and",
"8",
"men)",
"were",
"eligible,",
"consented,",
"and",
"included",
"in",
"the",
"study;",
"their",
"mean",
"age",
"(standard",
"deviation,",
"[SD])",
"was",
"56",
"years",
"(13.0",
"years).",
"All",
"patients",
"were",
"receiving",
"active",
"chemotherapy,",
"and",
"two",
"were",
"also",
"receiving",
"active",
"radiotherapy.",
"Chemotherapy",
"varied",
"according",
"to",
"the",
"primary",
"cancer",
"and",
"included",
"anthracycline,",
"platinum,",
"tax-",
"anes,",
"cyclophosphamide,",
"high-dose",
"ifosfamide,",
"vincristine,",
"vinblastine,",
"bleomycin,",
"and",
"others.",
"Many",
"of",
"the",
"included",
"patients",
"had",
"their",
"chemotherapy",
"treatment",
"as",
"second-",
"or",
"third-line",
"therapy.",
"Patients'",
"characteristics,",
"including",
"age,",
"primary",
"tumor,",
"and",
"active",
"anticancer",
"treatment",
"are",
"sum-",
"marized",
"in",
"Table",
"1.",
"One",
"patient",
"died",
"during",
"the",
"study",
"from",
"his",
"tumor",
"(after",
"week",
"2),",
"and",
"five",
"patients",
"withdrew",
"from",
"the",
"study",
"because",
"of",
"inconvenience",
"(three",
"after",
"week",
"3,",
"and",
"two",
"after",
"week",
"4).",
"Nineteen",
"(76.0%)",
"patients",
"completed",
"a",
"minimum",
"of",
"three",
"treat-",
"ments,",
"15",
"(60.0%)",
"completed",
"nine",
"treatments,",
"and",
"14",
"(56.0%)",
"completed",
"all",
"twelve",
"planned",
"weekly",
"treatments.",
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"2013:7",
"As",
"seen",
"in",
"Table",
"2,",
"the",
"mean",
"Hb",
"level",
"of",
"the",
"25",
"patients",
"at",
"baseline",
"was",
"9.6",
"g/dL",
"(median,",
"9.9",
"g/dL;",
"range,",
"6.9",
"g/dL–10.9",
"g/dL).",
"For",
"the",
"15",
"patients",
"who",
"completed",
"at",
"least",
"nine",
"treatments,",
"the",
"mean",
"change",
"in",
"their",
"Hb",
"level",
"was",
"1.7",
"g/dL",
"(median,",
"1.1",
"g/dL;",
"range,",
"−1.9",
"g/dL",
"to",
"3.2",
"g/dL).",
"For",
"the",
"14",
"patients",
"who",
"completed",
"the",
"whole",
"treatment",
"period",
"(12",
"weeks),",
"the",
"mean",
"Hb",
"level",
"change",
"was",
"2.1",
"g/dL",
"Table",
"2",
"Means",
"and",
"medians",
"of",
"hemoglobin",
"levels",
"(g/dL)",
"of",
"the",
"25",
"patients",
"with",
"cancer",
"Baseline",
"(week",
"1)",
"Week",
"3",
"Week",
"6",
"Week",
"9",
"Week",
"12",
"Patients,",
"n",
"Mean",
"g/dL",
"(SD)",
"Median",
"g/dL",
"(minimum,",
"maximum)",
"25",
"19",
"15",
"15",
"14",
"9.6",
"(1.06)",
"10.5",
"(1.28)",
"10.5",
"(1.12)",
"11.3",
"(1.37)",
"11.7",
"(1.22)",
"9.9",
"(6.90,10.9)",
"10.7",
"(6.80,12.1)",
"10.5",
"(9.10,12.0)",
"11.55",
"(8.90,13.2)",
"11.35",
"(9.80,13.7)",
"Abbreviations:",
"n,",
"number;",
"SD,",
"standard",
"deviation.",
"submit",
"your",
"manuscript",
"|",
"www.dovepress.com",
"Dovepress",
"941",
"Dovepress",
"Abdel-Razeq",
"et",
"al",
"(median,",
"1.3",
"g/dL;",
"range,",
"−0.2",
"g/dL",
"to",
"4.6",
"g/dL;",
"P",
"=",
"0.0007).",
"Eight",
"(42.1%)",
"of",
"the",
"19",
"patients",
"who",
"completed",
"at",
"least",
"three",
"iron",
"infusions",
"had",
"a",
"more",
"than",
"1",
"g/dL",
"increase",
"in",
"their",
"Hb",
"level.",
"Hemoglobin",
"level",
"changes",
"for",
"the",
"14",
"patients",
"who",
"completed",
"twelve",
"iron",
"infusions",
"are",
"shown",
"in",
"Figure",
"1.",
"No",
"IV",
"iron-related",
"adverse",
"events",
"were",
"reported",
"among",
"patients",
"during",
"the",
"study",
"or",
"the",
"follow-up",
"period.",
"TSAT",
"was",
"monitored",
"during",
"the",
"study",
"period,",
"and",
"no",
"patients",
"had",
"TSAT",
"levels",
"increase",
"to",
"more",
"than",
"50%.",
"The",
"highest",
"ferritin",
"level",
"among",
"patients",
"who",
"completed",
"at",
"least",
"nine",
"IV",
"iron",
"treatments",
"was",
"1,170",
"ng/mL;",
"the",
"mean",
"level",
"at",
"the",
"end",
"of",
"study",
"period",
"for",
"the",
"whole",
"group",
"was",
"379",
"ng/mL.",
"Five",
"(20.0%)",
"patients",
"received",
"blood",
"transfusions",
"and",
"were",
"considered",
"treatment",
"failures",
"(three",
"after",
"week",
"3,",
"transfused",
"at",
"Hb",
"levels",
"of",
"6.9",
"g/dL,",
"7.8",
"g/dL,",
"and",
"5.4",
"g/dL;",
"one",
"after",
"week",
"4,",
"transfused",
"at",
"an",
"Hb",
"level",
"of",
"8.2",
"g/dL;",
"and",
"one",
"after",
"week",
"9,",
"transfused",
"at",
"an",
"Hb",
"level",
"of",
"7.2",
"g/dL).",
"The",
"decision",
"for",
"transfusion",
"was",
"made",
"by",
"the",
"primary",
"treating",
"physician.",
"Discussion",
"Anemia",
"is",
"extremely",
"common",
"in",
"patients",
"with",
"cancer.",
"Low",
"Hb",
"levels",
"are",
"associated",
"with",
"diminished",
"QOL",
"and",
"possibly",
"decreased",
"overall",
"survival.",
"2",
"Successful",
"treatment",
"of",
"anemia",
"has",
"undeniable",
"benefits",
"for",
"patients,",
"often",
"yielding",
"dramatic",
"symptomatic",
"improvement.",
"Although",
"the",
"role",
"of",
"ESAs",
"is",
"well-established",
"in",
"treating",
"CAA,",
"big",
"concerns",
"were",
"recently",
"raised",
"about",
"the",
"negative",
"effect",
"of",
"ESAs",
"on",
"survival",
"in",
"some",
"patients",
"with",
"cancer.",
"9–11",
"Concerns",
"about",
"the",
"risk",
"for",
"throm-",
"boembolism",
"in",
"patients",
"with",
"cancer",
"with",
"higher",
"Hb",
"levels",
"who",
"are",
"receiving",
"ESA",
"were",
"also",
"addressed",
"in",
"many",
"trials.",
"22,23",
"In",
"addition,",
"the",
"possible",
"immunosuppressive",
"effects",
"of",
"blood",
"product",
"transfusions",
"that",
"may",
"have",
"relevance",
"to",
"neoplasia",
"progression",
"were",
"addressed",
"before.",
"24,",
"25",
"In",
"our",
"pilot",
"study,",
"we",
"tested",
"the",
"feasibility",
"of",
"using",
"iron",
"supplementation",
"alone",
"to",
"treat",
"anemia",
"in",
"patients",
"with",
"cancer",
"who",
"are",
"undergoing",
"chemotherapy",
"without",
"the",
"use",
"of",
"ESAs",
"or",
"blood",
"transfusion,",
"which",
"could",
"be",
"a",
"valid",
"alternative,",
"especially",
"for",
"patients",
"with",
"curable",
"cancers.",
"Oral",
"iron",
"is",
"easier",
"to",
"administer",
"and",
"relatively",
"inexpen-",
"sive,",
"but",
"low",
"patient",
"adherence,",
"poor",
"enteral",
"absorption,",
"and",
"poor",
"tolerance",
"because",
"of",
"a",
"wide",
"range",
"of",
"troublesome",
"gas-",
"trointestinal",
"adverse",
"effects",
"limit",
"its",
"overall",
"effectiveness.",
"26",
"Anemia",
"of",
"chronic",
"disease",
"may",
"occur",
"in",
"patients",
"with",
"cancer",
"and",
"is",
"associated",
"with",
"an",
"increase",
"in",
"hepcidin",
"lev-",
"els,",
"which",
"decreases",
"oral",
"iron",
"absorption",
"and",
"bone",
"marrow",
"iron",
"use,",
"negating",
"any",
"possible",
"effect",
"of",
"regular",
"doses",
"of",
"oral",
"iron.",
"15",
"IV",
"iron",
"therapy",
"significantly",
"improves",
"response",
"to",
"epo-",
"etin",
"alfa",
"when",
"compared",
"with",
"oral",
"iron",
"or",
"no",
"iron",
"in",
"anemic",
"patients",
"with",
"cancer",
"who",
"are",
"receiving",
"chemotherapy.",
"17–21",
"Oral",
"iron",
"supplements",
"with",
"ESAs",
"showed",
"no",
"significant",
"benefit",
"over",
"ESAs",
"alone",
"in",
"treating",
"CAA.",
"21",
"Sodium",
"ferric",
"gluconate",
"and",
"iron",
"sucrose",
"appear",
"to",
"have",
"more",
"favorable",
"safety",
"profiles",
"over",
"iron",
"dextran.",
"A",
"large",
"prospective",
"safety",
"comparison",
"trial",
"failed",
"to",
"show",
"serious",
"anaphylactoid",
"reactions,",
"27",
"which",
"is",
"confirmed",
"in",
"our",
"study,",
"in",
"which",
"no",
"patients",
"developed",
"reactions",
"and",
"no",
"patients",
"withdrew",
"from",
"the",
"study",
"because",
"of",
"adverse",
"effects.",
"Given",
"that",
"the",
"mean",
"Hb",
"increase",
"using",
"ESAs",
"with",
"IV",
"iron",
"in",
"one",
"large",
"controlled",
"trial",
"was",
"2.4",
"g/dL,",
"21",
"the",
"results",
"obtained",
"in",
"our",
"study",
"are",
"clinically",
"significant.",
"These",
"findings",
"should",
"be",
"further",
"confirmed",
"and",
"better",
"assessed",
"in",
"larger",
"studies,",
"in",
"which",
"questions",
"such",
"as",
"the",
"optimal",
"timing",
"of",
"IV",
"iron",
"therapy",
"with",
"respect",
"to",
"chemo-",
"therapy",
"and",
"the",
"optimal",
"total",
"dose",
"of",
"IV",
"iron",
"should",
"be",
"determined.",
"16",
"14",
"12",
"Hb",
"level",
"10",
"8",
"6",
"4",
"2",
"0",
"Baseline",
"Week",
"3",
"Week",
"6",
"Week",
"9",
"Week",
"12",
"Figure",
"1",
"Hemoglobin",
"(Hb)",
"level",
"changes",
"for",
"the",
"14",
"patients",
"who",
"completed",
"12",
"iron",
"infusions",
"(dotted",
"lines)",
"and",
"their",
"mean",
"hemoglobin",
"level",
"change",
"(solid",
"line).",
"942",
"submit",
"your",
"manuscript",
"|",
"www.dovepress.com",
"Dovepress",
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"2013:7",
"Dovepress",
"The",
"use",
"of",
"IV",
"iron",
"monotherapy",
"was",
"recently",
"reviewed",
"by",
"a",
"group",
"in",
"Germany",
"that",
"studied",
"the",
"use",
"of",
"ferric",
"car-",
"boxymaltose",
"to",
"replace",
"ESA",
"and",
"blood",
"transfusions",
"as",
"a",
"treatment",
"for",
"CAA.",
"Iron-deficient",
"patients",
"treated",
"with",
"ferric",
"carboxymaltose",
"alone",
"(n",
"=",
"233)",
"had",
"a",
"median",
"of",
"1.4",
"g/dL",
"increase",
"in",
"hemoglobin",
"levels",
"compared",
"with",
"those",
"receiving",
"additional",
"treatment",
"with",
"ESAs",
"(n",
"=",
"46;",
"median,",
"1.6",
"g/dL).",
"Our",
"study,",
"however,",
"is",
"peculiar",
"in",
"using",
"iron",
"therapy",
"in",
"a",
"non-iron-deficiency",
"state.",
"28",
"Iron",
"overload",
"after",
"IV",
"iron",
"therapy,",
"with",
"potential",
"con-",
"cerns",
"about",
"the",
"risk",
"of",
"developing",
"secondary",
"cancers",
"and",
"infection,",
"might",
"be",
"raised.",
"The",
"highest",
"serum",
"ferritin",
"level",
"in",
"the",
"present",
"study",
"in",
"patients",
"who",
"completed",
"at",
"least",
"9",
"weeks",
"of",
"IV",
"iron",
"therapy",
"was",
"1,170",
"ng/mL.",
"Most",
"of",
"the",
"literature",
"addressing",
"cancer",
"and",
"infections",
"in",
"iron-overloaded",
"patients",
"comes",
"from",
"patients",
"with",
"hemochromatosis",
"or",
"patients",
"who",
"are",
"undergoing",
"hemodialysis.",
"Published",
"reviews",
"report",
"an",
"increase",
"in",
"hepatocellular",
"only",
"in",
"patients",
"with",
"hemochromatosis",
"after",
"they",
"develop",
"cirrhosis.",
"29",
"Similarly",
"data",
"supporting",
"the",
"association",
"between",
"IV",
"iron",
"therapy",
"and",
"higher",
"infection",
"rate",
"are",
"weak",
"and",
"not",
"well-supported.",
"30",
"In",
"fact,",
"anemia",
"itself",
"is",
"a",
"risk",
"factor",
"for",
"infections",
"in",
"patients",
"receiving",
"hemodialysis.",
"31",
"A",
"multivariate",
"analysis",
"of",
"associa-",
"tions",
"between",
"iron",
"and",
"mortality",
"in",
"more",
"than",
"58,000",
"patients",
"receiving",
"hemodialysis",
"reported",
"no",
"increased",
"death",
"rate",
"from",
"serum",
"ferritin",
"levels",
"as",
"high",
"as",
"1,200",
"ng/mL.",
"30",
"The",
"increasing",
"cost",
"of",
"therapy",
"in",
"patients",
"with",
"cancer",
"is",
"of",
"grave",
"concern,",
"which",
"could",
"be",
"an",
"additional",
"benefit",
"of",
"IV",
"iron",
"over",
"the",
"use",
"of",
"ESAs",
"in",
"such",
"patients.",
"To",
"further",
"address",
"many",
"of",
"the",
"questions",
"raised,",
"our",
"team",
"is",
"planning",
"a",
"bigger",
"trial",
"for",
"IV",
"iron",
"in",
"patients",
"with",
"cancer",
"who",
"have",
"anemia",
"to",
"confirm",
"the",
"results",
"discussed",
"in",
"this",
"pilot",
"trial.",
"In",
"addition,",
"we",
"will",
"be",
"looking",
"into",
"predictors",
"of",
"response",
"to",
"IV",
"iron,",
"such",
"as",
"serum",
"hepcidin",
"level.",
"Conclusion",
"IV",
"iron",
"therapy",
"alone",
"is",
"safe",
"and",
"may",
"be",
"effective",
"in",
"improv-",
"ing",
"Hb",
"levels",
"in",
"patients",
"with",
"cancer",
"who",
"are",
"undergoing",
"active",
"anticancer",
"therapy.",
"Further",
"randomized",
"trials",
"are",
"needed",
"to",
"address",
"many",
"of",
"the",
"questions",
"raised",
"in",
"our",
"pilot",
"study.",
"Disclosure",
"The",
"authors",
"report",
"no",
"conflicts",
"of",
"interest",
"in",
"this",
"work.",
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"Drug",
"Design,",
"Development",
"and",
"Therapy",
"Publish",
"your",
"work",
"in",
"this",
"journal",
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"is",
"an",
"international,",
"peer-",
"reviewed",
"open-access",
"journal",
"that",
"spans",
"the",
"spectrum",
"of",
"drug",
"design",
"and",
"development",
"through",
"to",
"clinical",
"applications.",
"Clinical",
"outcomes,",
"patient",
"safety,",
"and",
"programs",
"for",
"the",
"development",
"and",
"effective,",
"safe,",
"and",
"sustained",
"use",
"of",
"medicines",
"are",
"a",
"feature",
"of",
"the",
"journal,",
"which",
"has",
"also",
"been",
"accepted",
"for",
"indexing",
"on",
"PubMed",
"Central.",
"The",
"manu-",
"script",
"management",
"system",
"is",
"completely",
"online",
"and",
"includes",
"a",
"very",
"quick",
"and",
"fair",
"peer-review",
"system,",
"which",
"is",
"all",
"easy",
"to",
"use.",
"Visit",
"http://www.dovepress.com/testimonials.php",
"to",
"read",
"real",
"quotes",
"from",
"published",
"authors.",
"Submit",
"your",
"manuscript",
"here:",
"http://www.dovepress.com/drug-design-development-and-therapy-journal",
"944",
"submit",
"your",
"manuscript",
"|",
"www.dovepress.com",
"Dovepress",
"Drug",
"Design,",
"Development",
"and",
"Therapy",
"2013:7"
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] | Background Anemia in patients with cancer who are undergoing active therapy is commonly encountered and may worsen quality of life in these patients. The effect of blood transfusion is often temporary and may be associated with serious adverse events. Erythropoiesis-stimulating agents are not effective in 30 | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/95/97/PMC3770628.tar.gz |
PMC4307954 | ["Epilepsy","&","Behavior","Case","Reports","2","(2014)","124–126","Contents","lists","available",(...TRUNCATED) | [[219,38,243,44],[245,38,249,44],[251,38,276,44],[278,38,290,44],[292,38,314,44],[315,38,319,44],[32(...TRUNCATED) | [[368,47,408,55],[411,47,418,55],[421,47,463,55],[467,47,487,55],[490,47,527,55],[529,47,536,55],[53(...TRUNCATED) | "We present an unusual case of recurrent cough syncope in a 43-year-old woman, which was initially t(...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/cf/main.PMC4307954.pdf |
PMC4789428 | ["Hindawi","Publishing","Corporation","Nursing","Research","and","Practice","Volume","2016,","Articl(...TRUNCATED) | [[51,50,79,58],[80,50,115,58],[116,50,156,58],[51,59,77,67],[78,59,107,67],[108,59,120,67],[122,59,1(...TRUNCATED) | [[85,62,131,72],[133,62,191,72],[193,62,260,72],[85,73,128,83],[130,73,178,83],[180,73,200,83],[203,(...TRUNCATED) | " Objective. The objective of this study was to describe the recent clinical characteristics of labo(...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/ca/f8/PMC4789428.tar.gz |
PMC4217354 | ["Hindawi","Publishing","Corporation","Journal","of","Lipids","Volume","2014,","Article","ID","86431(...TRUNCATED) | [[51,50,79,58],[80,50,115,58],[116,50,156,58],[51,59,74,67],[76,59,82,67],[84,59,104,67],[51,69,76,7(...TRUNCATED) | [[85,63,131,73],[133,63,191,73],[193,63,260,73],[85,74,123,84],[126,74,136,84],[140,74,173,84],[85,8(...TRUNCATED) | "Lipid apheresis is used to treat patients with severe hyperlipidemia by reducing low-density lipopr(...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/50/1e/PMC4217354.tar.gz |
PMC3133512 | ["International","Journal","of","General","Medicine","Dovepress","open","access","to","scientific","(...TRUNCATED) | [[71,42,149,57],[152,42,194,57],[197,42,209,57],[212,42,258,57],[261,42,316,57],[497,42,558,57],[424(...TRUNCATED) | [[116,53,243,71],[248,53,316,71],[321,53,341,71],[346,53,421,71],[426,53,516,71],[812,53,911,71],[69(...TRUNCATED) | "Background: Agenesis of the inferior vena cava (IVC) as a cause of recurrent deep vein thrombosis ((...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/14/de/PMC3133512.tar.gz |
PMC3109876 | ["SAGE-Hindawi","Access","to","Research","International","Journal","of","Alzheimer's","Disease","Vol(...TRUNCATED) | [[51,45,100,53],[102,45,122,53],[124,45,131,53],[132,45,161,53],[51,54,93,62],[95,54,118,62],[120,54(...TRUNCATED) | [[85,56,166,66],[170,56,203,66],[206,56,218,66],[220,56,268,66],[85,68,155,78],[158,68,196,78],[200,(...TRUNCATED) | "We examined the usefulness of brief neuropsychological tests and serum Aβ as a predictive test for(...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/59/8b/PMC3109876.tar.gz |
PMC4033428 | ["Hindawi","Publishing","Corporation","Journal","of","Skin","Cancer","Volume","2014,","Article","ID"(...TRUNCATED) | [[51,50,79,58],[80,50,115,58],[116,50,156,58],[51,59,74,67],[76,59,82,67],[84,59,98,67],[100,59,123,(...TRUNCATED) | [[85,63,131,73],[133,63,191,73],[193,63,260,73],[85,74,123,84],[126,74,136,84],[140,74,163,84],[166,(...TRUNCATED) | "We have previously demonstrated that Rad6 and β-catenin enhance each other's expression through a (...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/29/fa/PMC4033428.tar.gz |
PMC3056325 | ["International","Journal","of","General","Medicine","Dovepress","open","access","to","scientific","(...TRUNCATED) | [[71,42,149,57],[152,42,194,57],[197,42,209,57],[212,42,258,57],[261,42,316,57],[497,42,558,57],[424(...TRUNCATED) | [[116,53,243,71],[248,53,316,71],[321,53,341,71],[346,53,421,71],[426,53,516,71],[812,53,911,71],[69(...TRUNCATED) | "Background A review of the literature and an extensive Medline search revealed that this is the fir(...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/fc/93/PMC3056325.tar.gz |
PMC2778185 | ["Hindawi","Publishing","Corporation","Journal","of","Environmental","and","Public","Health","Volume(...TRUNCATED) | [[51,45,78,52],[80,45,114,52],[116,45,156,52],[51,54,74,62],[76,54,83,62],[85,54,133,62],[134,54,146(...TRUNCATED) | [[85,56,130,65],[133,56,190,65],[193,56,260,65],[85,68,123,78],[126,68,138,78],[141,68,221,78],[223,(...TRUNCATED) | "This was a cross-sectional study that investigated pesticide exposure and its risk factors targetin(...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_package/63/57/PMC2778185.tar.gz |
PMC3794340 | ["European","Journal","of","Histochemistry","2013;","volume","57:e14","Stem","cell","populations","i(...TRUNCATED) | [[344,25,380,35],[383,25,412,35],[414,25,422,35],[425,25,482,35],[485,25,506,35],[509,25,536,35],[53(...TRUNCATED) | [[556,30,614,42],[619,30,666,42],[669,30,682,42],[687,30,779,42],[784,30,818,42],[823,30,867,42],[87(...TRUNCATED) | "Cardiac progenitor cells are multipotent stem cells isolated from both embryonic and adult hearts i(...TRUNCATED) | ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0b/a2/ejh-2013-2-e14.PMC3794340.pdf |
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