Chemotherapy selectivity

There is a growing number of published examples of the utility of screening patients for pharmacogenetic markers prior to chemotherapy selection (1). Many published markers of association with chemotherapy outcome or toxicity still require validation in prospective studies. Examples of well-characterized pharmacogenetic markers include thiopurine methyltransferase (TPMT), UGT (uridine diphosphate [UDP]-glucuronosyltransferase) lAl, and epidermal growth factor receptor (EGER). 

From 1904 onwards Ehrlich concerned himself chiefly with chemotherapy, selecting trypanosomiasis in the mouse as his principal model. Conditions for this work were poor in his Institute, and became steadily worse. However, in 1906 his gloom was dispersed by the splendid action of a benefactor, Frau Franziska Speyer who had come to regard Ehrlich s work with the greatest... 

Suzuki, M., Hori, K., Abe, Z., Saito, S., and Sato, H., 1981, A new approach to cancer chemotherapy selective enhancement of tumor blood flow with angiotensin II. 7. Natl. Cancer Inst. 67 663-669. 

Fluorinated Heterocyclic Compounds. HeterocycHc compounds containing the CF group are prepared by methods similar to those used in the fluorination of aHphatic compounds. The direct action of fluorine on uracil yields the cancer chemotherapy agent, 5-fluorouracil [51-21-8] as one special example of a selective fluorination on a commercial scale (25). 

CarbocycHc 2/3 -didehydro-2/3 -dideoxyguanosine [118353-05-2] (carbovk, CBV, 66), C H 2N502, synthesized in 1988 (177), is a promising candidate for the chemotherapy of AIDS. CBV inhibits HIV repHcation and HIV-induced cytopathic effects in a variety of human T-lymphoblastoid ceU lines at concentrations approximately two hundred- to four hundredfold below its cytotoxic concentrations (177). CBV is as effective as AZT and DDC in reducing the expression of vkal antigen in HIV-infected CEM ceUs (177). The antivkal potency and selectivity of carbovk is comparable to the anti-HIV-1 potency and selectivity of 2/3 -dideoxyadenosine (178). The exact mode of antivkal action of carbovk has not yet been elucidated, but may be the modulating effect of intraceUular nucleotides on 5 -nucleotidase activity (179). 

Treatment for tumor patients with synthetic drags -chemotherapeutics - that may be of completely different chemical structure. The main goal of tumor chemotherapy is to achieve a selective toxicity for the tumor without causing damage to the host, for instance by combining several cytostatic drags at doses lower than required for monotherapy. 

De Clercq E, Eield H J (2006) Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy. Brit J Pharmacol 147 1-11 De Clercq E, Hol A, Rosenberg I, Sakuma T, Balzarini J, Maudgal PC (1986) A novel selective broad-spectrum anti-DNA virus agent. Nature 323 464 67 De Clercq E, Sakuma T, Baba M, Pauwels R, Balzarini J, Rosenberg I, Hol A (1987) Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res 8 261-272... 

Partaledis JA, Yamaguchi K, Tisdale M, Blair EE, Falcione C, Maschera B, Myers RE, Pazhanisamy S, Futer O, CuHinan AB et al (1995) In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydrox-yethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. J Virol 69 5228-5235 Patick AK (2006) Rhinovirus chemotherapy. Antiviral Res 71 391-396... 

L-Asparaginase, an enzyme derived from E. coli or Erwinia carotovora, has been employed in cancer chemotherapy where its selectivity depends upon the essential requirement of some tumours for the amino acid L-asparagine. Normal tissues do not require this amino acid and thus the enzyme is administered with the intention of depleting tumour cells of asparagine by converting it to aspartic acid and ammonia. Whilst L-asparaginase showed promise in a variety of experimentally induced tumours, it is only useful in humans for the treatment of acute lymphoblastic leukaemia, although it is sometimes used for myeloid leukaemia. 

Laboratory monitoring is performed before initiating therapy and before each cycle of chemotherapy. A complete blood count should be obtained prior to each course of chemotherapy to ensure that hematologic values are adequate. In particular, white blood cell counts and absolute neutrophil counts can be decreased in patients receiving chemotherapy such as irinote-can and 5-FU and increase the risk of infection. Baseline liver function tests and an assessment of renal function should be done prior to and periodically during therapy. Other selected laboratory tests include checking for the presence of protein in the urine in patients receiving oxaliplatin and bevacizumab. 

P2-microglobulin concentration have been correlated with survival. The International Index is a predictive model for aggressive NHL to be treated with doxorubicin-containing chemotherapy regimens.11 This index is used as a tool for selecting therapy for patients who may warrant a more intense treatment regimen based on known poor prognostic factors. 

Judicious selection of treatment options to avoid long-term toxicity because patients may require several different chemotherapy treatment regimens over a period of years for low-grade NHL... 

Discuss the side-effect profile and administration schedule of each agent and how this information would help in selection of her next chemotherapy regimen... 

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