Causes for increased myelosuppression with increasing age in patients with oesophageal cancer treated by chemoradiotherapy
The aim of this study was to identify why increasing myelosuppression accompanies increasing age in patients treated for oesophageal cancer by chemoradiation. Weekly neutrophil and platelet counts were obtained throughout treatment in 86 patients undergoing chemoradiation without surgery for oesopha...
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Published in | European journal of cancer (1990) Vol. 35; no. 6; pp. 921 - 927 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Oxford
Elsevier Ltd
01.06.1999
Elsevier |
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Abstract | The aim of this study was to identify why increasing myelosuppression accompanies increasing age in patients treated for oesophageal cancer by chemoradiation. Weekly neutrophil and platelet counts were obtained throughout treatment in 86 patients undergoing chemoradiation without surgery for oesophageal cancer. One or two cycles of cisplatin 80
mg/m
2/day followed by 5-fluorouracil 800
mg/m
2/day for 4–5 days were administered during the first and fourth or fifth week of radiotherapy using 2
Gy daily fractions. 44 of the patients underwent 5-fluorouracil pharmacokinetic studies. Multiple regression procedures were used to determine the strength of factors that contribute to initial and nadir neutrophil and platelet counts. The kinetics of myeloid response were evaluated from the rates of disappearance and re-appearance of neutrophils and platelets during treatment. Age, fluorouracil dose (or AUC), baseline body weight and neutrophil (or platelet) count were found to be powerfully and independently predictive of both first neutrophil and platelet nadir count. Baseline neutrophil and platelet counts were also found to correlate negatively with advancing age independently of other factors. The rate of descent of both indices, however, was independent of age, baseline count and fluorouracil dose suggesting that variations in the size of the myeloproliferative compartment prior to treatment were responsible for interpatient variations. In addition, the rate of recovery of both indices was not influenced by age amongst patients in whom data was assessable suggesting that proliferation of surviving marrow elements is not compromised by age. These data are compatible with the hypothesis that a progressive depletion of the myeloid stem cell compartment accompanies advancing age, and that this is responsible for increasing myelotoxicity. |
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AbstractList | The aim of this study was to identify why increasing myelosuppression accompanies increasing age in patients treated for oesophageal cancer by chemoradiation. Weekly neutrophil and platelet counts were obtained throughout treatment in 86 patients undergoing chemoradiation without surgery for oesophageal cancer. One or two cycles of cisplatin 80
mg/m
2/day followed by 5-fluorouracil 800
mg/m
2/day for 4–5 days were administered during the first and fourth or fifth week of radiotherapy using 2
Gy daily fractions. 44 of the patients underwent 5-fluorouracil pharmacokinetic studies. Multiple regression procedures were used to determine the strength of factors that contribute to initial and nadir neutrophil and platelet counts. The kinetics of myeloid response were evaluated from the rates of disappearance and re-appearance of neutrophils and platelets during treatment. Age, fluorouracil dose (or AUC), baseline body weight and neutrophil (or platelet) count were found to be powerfully and independently predictive of both first neutrophil and platelet nadir count. Baseline neutrophil and platelet counts were also found to correlate negatively with advancing age independently of other factors. The rate of descent of both indices, however, was independent of age, baseline count and fluorouracil dose suggesting that variations in the size of the myeloproliferative compartment prior to treatment were responsible for interpatient variations. In addition, the rate of recovery of both indices was not influenced by age amongst patients in whom data was assessable suggesting that proliferation of surviving marrow elements is not compromised by age. These data are compatible with the hypothesis that a progressive depletion of the myeloid stem cell compartment accompanies advancing age, and that this is responsible for increasing myelotoxicity. The aim of this study was to identify why increasing myelosuppression accompanies increasing age in patients treated for oesophageal cancer by chemoradiation. Weekly neutrophil and platelet counts were obtained throughout treatment in 86 patients undergoing chemoradiation without surgery for oesophageal cancer. One or two cycles of cisplatin 80 mg/m2/day followed by 5-fluorouracil 800 mg/m2/day for 4-5 days were administered during the first and fourth or fifth week of radiotherapy using 2 Gy daily fractions. 44 of the patients underwent 5-fluorouracil pharmacokinetic studies. Multiple regression procedures were used to determine the strength of factors that contribute to initial and nadir neutrophil and platelet counts. The kinetics of myeloid response were evaluated from the rates of disappearance and re-appearance of neutrophils and platelets during treatment. Age, fluorouracil dose (or AUC), baseline body weight and neutrophil (or platelet) count were found to be powerfully and independently predictive of both first neutrophil and platelet nadir count. Baseline neutrophil and platelet counts were also found to correlate negatively with advancing age independently of other factors. The rate of descent of both indices, however, was independent of age, baseline count and fluorouracil dose suggesting that variations in the size of the myeloproliferative compartment prior to treatment were responsible for interpatient variations. In addition, the rate of recovery of both indices was not influenced by age amongst patients in whom data was assessable suggesting that proliferation of surviving marrow elements is not compromised by age. These data are compatible with the hypothesis that a progressive depletion of the myeloid stem cell compartment accompanies advancing age, and that this is responsible for increasing myelotoxicity. |
Author | Ackland, S.P Walpole, E Spry, N.A Denham, J.W Lamb, D.S Burmeister, B Dady, P |
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Cites_doi | 10.1016/0360-3016(94)00449-U 10.1016/0921-8734(91)90032-7 10.1084/jem.178.3.787 10.1016/0047-6374(86)90116-8 10.1073/pnas.92.1.258 10.1073/pnas.91.21.9857 10.1111/j.1440-1673.1996.tb00440.x 10.1016/0167-8140(96)01762-8 10.1093/ajcp/43.4.326 10.1182/blood.V82.9.2601.2601 10.1128/IAI.63.1.104-109.1995 10.1006/abio.1996.9943 |
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Keywords | myelotoxicity age effects chemoradiation oesophageal cancer Antineoplastic agent Human Squamous cell carcinoma Toxicity Esophageal disease Hemopathy Malignant tumor Radiotherapy Esophagus Chemotherapy Bone marrow Digestive diseases Myelosuppression Combined treatment Age |
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USA doi: 10.1073/pnas.91.21.9857 contributor: fullname: Vaziri – volume: 55 start-page: 876 year: 1994 ident: 10.1016/S0959-8049(99)00065-9_BIB18 article-title: Genetic determination of telomere size in humans: a twin study of three age groups publication-title: Am. J. Hum. Genet. contributor: fullname: Slagboom – volume: 20 start-page: 376 year: 1994 ident: 10.1016/S0959-8049(99)00065-9_BIB17 article-title: Age-related decline in proliferative potential of purified stem cell candidates publication-title: Blood Cells contributor: fullname: Lansdorp – volume: 40 start-page: 424 year: 1996 ident: 10.1016/S0959-8049(99)00065-9_BIB3 article-title: Concurrent chemo-radiation for oesophageal cancer—factors influencing myelotoxicity publication-title: Australas. Radiol. doi: 10.1111/j.1440-1673.1996.tb00440.x contributor: fullname: MacKean – volume: 40 start-page: 31 year: 1996 ident: 10.1016/S0959-8049(99)00065-9_BIB2 article-title: Factors influencing outcome following radio-chemotherapy for oesophageal cancer publication-title: Radiother. Oncol. doi: 10.1016/0167-8140(96)01762-8 contributor: fullname: Denham – volume: 10 start-page: S30 issue: Suppl. 1 year: 1996 ident: 10.1016/S0959-8049(99)00065-9_BIB6 article-title: The hematopoietic stem cell in elderly patients with leukemia publication-title: Leukemia contributor: fullname: Keating – volume: 52 start-page: 661 year: 1993 ident: 10.1016/S0959-8049(99)00065-9_BIB13 article-title: Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes publication-title: Am. J. Hum. Genet. contributor: fullname: Vaziri – volume: 43 start-page: 326 year: 1965 ident: 10.1016/S0959-8049(99)00065-9_BIB5 article-title: Normal variations with aging of the amount of hemopoietic tissue in bone marrow from the anterior iliac crest publication-title: Am. J. Clin. Path. doi: 10.1093/ajcp/43.4.326 contributor: fullname: Hartsock – volume: 82 start-page: 2601 year: 1993 ident: 10.1016/S0959-8049(99)00065-9_BIB9 article-title: Hematopoiesis in the aged: A model of hematopoietic dysregulation? publication-title: Blood doi: 10.1182/blood.V82.9.2601.2601 contributor: fullname: Rothstein – volume: 63 start-page: 104 year: 1995 ident: 10.1016/S0959-8049(99)00065-9_BIB10 article-title: Cytokines and progenitor cells of granulocytopoisesis in peripheral blood of patients with bacterial infections publication-title: Infect. Immun. doi: 10.1128/IAI.63.1.104-109.1995 contributor: fullname: Selig – volume: 246 start-page: 79 year: 1997 ident: 10.1016/S0959-8049(99)00065-9_BIB4 article-title: Simultaneous determination of dihydrofluorouracil and 5-Fluorouracil in plasma by high-performance liquid chromatography publication-title: Anal. Biochem. doi: 10.1006/abio.1996.9943 contributor: fullname: Ackland |
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SubjectTerms | Adult age effects Age Factors Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - adverse effects Biological and medical sciences chemoradiation Cisplatin - administration & dosage Combined Modality Therapy Drug toxicity and drugs side effects treatment Esophageal Neoplasms - drug therapy Esophageal Neoplasms - radiotherapy Female Fluorouracil - administration & dosage Humans Lymphocyte Count Male Medical sciences Middle Aged myelotoxicity Neutropenia - chemically induced Neutropenia - etiology oesophageal cancer Pharmacology. Drug treatments Platelet Count Thrombocytopenia - chemically induced Thrombocytopenia - etiology Toxicity: blood |
Title | Causes for increased myelosuppression with increasing age in patients with oesophageal cancer treated by chemoradiotherapy |
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