By Jacob J. Lokich M.D. (auth.)

Chemotherapy for-cancer is in a country of evolution. simply because a few cancers can now be cured with chemotherapy as a novel modality, this treatment can not be considered as easily a palliative contribution. Chemotherapy has assumed an incredible position as an adjuvant to different modalities, together with either surgical procedure and radiation treatment. For a few tumors, the first software of chemotherapy in a mixed modality method of healing remedy has ended in the applying of much less radical surgical procedure whereas reaching sizeable of quite infrequent tumors corresponding to therapy premiums. still, with the exception early life tumors, hematologic malignancies, and testicular melanoma, the effec­ tiveness of chemotherapy in so much tumors is seriously restricted. on the mobile point, better realizing of the explicit mechanism of tumor phone killing and of the phenomenon of drug resistance are elusive, severe elements within the development of effectiveness in melanoma chemotherapy. Prolonging the publicity time of the tumor mobilephone to medicines is an idea that used to be addressed within the early levels of the improvement of chemotherapy. How­ ever, technological boundaries inhibited the wider program of chemother­ apy by way of infusion until eventually fresh years. additionally, the benefit of intermittent ther­ apy on an outpatient foundation, with the primary idea of drug impact in accordance with a dose reaction in addition to the confirmed effectiveness of this time table in a few tumors, has slowed the method of subjecting infusion chemotherapy to the trials of medical trials.

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30 IN VIVO DATA Momparier and Gonzalez 31 treated L121O-bearing mice with 1- to 8-hour infusions of 5-aza-2'-deoxycytidine. " However, equitoxic bolus or short infusion treatments were not tested. They noted that the plasma elimination half-life of 5-aza-2'-deoxycytidine in mice (measured by bioassay) was only 40 minutes, giving additional support to the use of continuous infusion for this drug. 6-mercaptopurine and 6-thioguanine These two drugs are older agents, usually administered in single!

Despite their similar structures, these drugs have very different pharmacokinetic and clinical properties. VCR is predominantly neurotoxic, whereas VLB is myelosuppressive, with occasional neurotoxicity. In general, vindesine's properties are intermediate between the other 2 drugs. 57 In addition, the cellular retention of these drugs is different, with VLB being rapidly released from cells and VCR released relatively slowly. 59 As would be expected from the known phase specificity of these drugs, there are multiple in vitro studies demonstrating exposure time-dependent cytotoxicity.

Similar results were obtained by Drewinko et aV placing ara-C into the group of "ineffectual" agents following a I-hour exposure. 23 Greenburg et aP obtained similar results using granulocyte progenitor cells. There is a consistently increased pharmacologic effect with prolonged exposure in vitro, and both the cytotoxicity and host toxicity would be predicted to be increased by continuous infusion. However, no conclusion can be drawn regarding changes in the therapeutic index based on in vitro studies alone.

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Cancer Chemotherapy by Infusion by Jacob J. Lokich M.D. (auth.)
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