By Branimir Ivan Sikic (auth.), C. Julian Rosenthal M.D., Marvin Rotman M.D. (eds.)
The first convention on concomitant infusion chemotherapy and radia tion remedy was once equipped with the goal of bringing jointly a few of the investigators who've validated, over the past few years, the hypo thesis that non-stop infusion chemotherapy may possibly modulate the cytotoxic impact of radiation treatment to the purpose of getting a strongly additive, if now not synergistic task on yes malignant tumors. This quantity represents the exact complaints of this convention provided in a manner that gives the reader a assessment of the on-going re seek within the box. we have now under pressure a couple of matters from easy biologic study and impact of mobilephone kinetics to the sensible equipment of drug supply structures and early scientific reports. the explanation for this new form of mixed modality remedy has been provided by means of a few of its pioneers. Early medical investigations in addition to the initial information of many who haven't but thoroughly matured have additionally been integrated. The reader may still examine those facts with a few reser vations. finally, those effects has to be proven by means of higher potential randomized reports with right controls sooner than turning into accredited because the therapy of selection in in the neighborhood complex tumors.
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Additional info for Clinical Applications of Continuous Infusion Chemotherapy and Concomitant Radiation Therapy
Gabriel Hortobagyi. 19 There were two sequential studies: the first with standard-infusion adriamycin, and the second with continuous 48-96 hour infusion. The second dose of 5FU was given on day 5, at the end of the 96-hour adriamycin infusion, an insignificant change from the day 8, used in standard FAC. The treatments were otherwise identical, including the intensification therapy, the concomitant hormonal therapy for ER-positive or -unknown patients, etc. With standard FAC we stopped adriamycin at 450 mg/m 2 , going on to CMF.
When analogous experiments were carried out in Balb/c and C57Bl/6J mice, the c onc urre nt admi ni stra ti on of dThd reduced the FUra LD 50 by 40% and 35% respectively (26). v. infusion. The MTD was reduced by the concurrent admi ni stration of dThd by 28-36%. i!! vivo toxicity of FUra. Tab12 2. v infusion of FUra to rats and mice. Animal Strain Fi sher CDF rats Balb/c mice C57Bl/6J mice FUra 50 50 58 MTD (mg/kg/d) FUra + dThd 33 33 42 The results of the antitumor activity of FUra administered alone and in comhination with dThd to mice bearing colon tumors No.
Although generally employed on a standard intermittent bolus schedule, preclinical studies in L1210 leukemia has demonstrated marked schedule dependency for this agent (10), supporting a rationale for continuous infusion. In addition, pharmacokinetic studies have demonstrated a relatively short plasma half-life of approximately one hour (T one-half alpha) and five hours (T one-half beta) (11). Clinical trials employing a variety of schedules with bolus delivery in small cell carcinoma indicate a higher response rate with a consecutive or every other day regimen compared to a weekly regimen (12).