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 treatment was once geared up with the goal of bringing jointly many of the investigators who've demonstrated, over the past few years, the hypo thesis that non-stop infusion chemotherapy may perhaps modulate the cytotoxic impression of radiation remedy to the purpose of getting a strongly additive, if now not synergistic task on sure malignant tumors. This quantity represents the particular court cases of this convention offered in a manner that gives the reader a overview of the on-going re seek within the box. we have now under pressure a few topics from easy biologic learn and impact of mobile kinetics to the sensible equipment of drug supply structures and early scientific reviews. the reason 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 facts of many who haven't but thoroughly matured have additionally been integrated. The reader may still examine those facts with a few reser vations. eventually, those effects has to be proven through better potential randomized reviews with right controls earlier than changing into authorized because the remedy of selection in in the neighborhood complex tumors.
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Extra resources for Clinical Applications of Continuous Infusion Chemotherapy and Concomitant Radiation Therapy
20. T. Effect of excess folates and deoxyinosine on the activity and site of action of 5-fluorouracil. Cancer Res. 41:3288-3295, 1981. 21. T. Relationship of cellular folate cofactor pools to activity of 5-fluorouracil. Mol. Pharmacol. 23:190-197, 1983. 22. M. A method for continuous drug infusion in unrestrained rats: its application in evaluating the toxicity of 5-fluorouracil/thymidine combination. J. Lab. Clin. Med. 93:1047-1053, 1979. 23. J. Clinical pharmacological studies of concurrent infusion of 5-fluorouracil and thymidine in treatment of colorectal carcinomas.
The only reasonable explanation is that there is a lower peak drug level, and there is time for the peak to be eliminated before the next dose. The best ,;ray to limit peak drug levels is to give a continuous infusion because the peak is inversely proportional to the time over which drug is given. We started a study, therefore, using adriamycin as a continuous infusion at a fixed dose of 60 mg/m 2 as a single agent in patients with CMF-resistant breast cancer. 16 All patients were required to have central venous catheters.
Infusion No. M. Toxicity (1) G. I. Toxicity ( 2) Ref. 30 149 pts. V. Push 20-25mg/kg 2hr Inf. 63% 39% 50% 33% Ref. 31 70 pts. V. Push 30mg/kg 52 days Inf. 72% 12% 8% 65% Ref. 32 18 pts. V. Push 27-30mg/kg 4 days Inf. 43% 33% 0% 50% (1) WBC <4000 mmc except Ref. 32 (WBC <3000 mmc) (2) Mucositis, moderate to severe With respect to FUra, there are several substances which can theoretically modulate its activity. metabolic modulations. (I) Chart 2 illustrates three examples of Thymidine (dThd) when administered con- currently with FUra, results in reduction of inhibition of DNA synthesis, due to bypass of FdUMP-inhibited dTMP synthesis.