title: Causes for increased myelosuppression with increasing age in patients with oesophageal cancer treated by chemoradiotherapy.
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/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.
authors.affiliation: Newcastle Mater Misericordiae Hospital, Hunter Region Mail Centre, Waratah NSW, Australia. mdjwd@cc.newcastle.edu.au
authors.forename: J W
authors.initials: JW
authors.lastname: Denham
authors.forename: S P
authors.initials: SP
authors.lastname: Ackland
authors.forename: B
authors.initials: B
authors.lastname: Burmeister
authors.forename: E
authors.initials: E
authors.lastname: Walpole
authors.forename: D S
authors.initials: DS
authors.lastname: Lamb
authors.forename: P
authors.initials: P
authors.lastname: Dady
authors.forename: N A
authors.initials: NA
authors.lastname: Spry
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000209:etiology*; D010976:Platelet Count; D013921:Thrombocytopenia / Q000139:chemically induced / Q000209:etiology*
chemical_list: D002945:Cisplatin; D005472:Fluorouracil