Leukemia acute myelocytic, treatment

Uniabeied Uses Treatment of acute myelocytic leukemia bladder, cervical, ovarian, prostatic, renal, and testicular carcinomas psoriatic arthritis systemic dermatomyo-sitis... 

Rozemuller, H., W.I Rombouts, IP. Touw, D.I FitzGerald, R.I Kreitman, I. Pastan, A. Hagenbeek, and A.C. Martens, Treatment of acute myelocytic leukemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukemia model. Leukemia, 1996.10(11) 1796-803. 

Leukemia cutis is very rare in acute myelocytic leukemia. Cutaneous relapse in acute promyelocytic leukemia has been reported during a period of complete hematological remission after treatment with tretinoin (100). 

Idarubicin, an antibiotic with antineoplastic activity (12 mg/m2 daily by slow IV injection), is indicated in the treatment of acute myelocytic leukemia in adults, including fragment, antigen-binding, classification M through M , in combination with other approved antileukemic agents. 

Daunorubicin (1) is a particularly efficient agent in the treatment of acute myelocytic and lymphocytic leukemia. Doxorubicin (2) exhibits a broader spectrum of action, including many solid tumors, and is currently used in the control of breast, ovary, thyroid and lung carcinoma as well as in the treatment of several blood cancers [6],... 

After toxicological studies in large animals, a Phase I study was started at the Lilly Laboratories for Clinical Research (6) with eight patients with a variety of cancers Subsequently, Phase I studies were conducted in several research centers, including ours (7, 8). These reports provide data on drug doses and schedules used, observed systemic toxicity (mainly mucocutaneous toxicity and myelosuppression), and reasons for discontinuation of PF treatment. Our recommended dose is 250 mg/m i,v. bolus, q 2-3 wk. Of the approximately 100 patients treated to-date, partial response was shown in patients with breast carcinoma (8) acute myelocytic leukemia (9) and Hodgkin s Diseases (5). 

Apart from DNA methylation studies, the second aspect of epigenetic misregulation involves disruption of histone acetylation and chromatin structure. Functional disruption of some HATs genes (such as the CBP and p300) is detected in some cancers, most notably, acute pro-myelocytic leukemia (51). This has lead to the hope that HD AC inhibitors will be useful for the treatment of this disease and a number of inhibitors are currently being assessed in clinical trials (see below). 

Harringtonine appears to be the most effective agent and recent studies in the People s Republic of China have shown that it is effective against L615 leukemia, L7212 leukemia, sarcoma 180, and Walker carcinosarcoma 256 (188). Harringtonine also appeared to be effective in the treatment of acute and chronic myelocytic leukemia in humans (189). 

Therapeutic applications Applications for these two agents differ despite their structural similarity and their apparently similar mechanisms of action. Doxorubicin is one of the most important and widely used anticancer drugs. It is used for treatment of sarcomas and a variety of carcinomas, including breast and lung, as well as acute lymphocytic leukemia and lymphomas. Daunorubicin is used in the treatment of acute lymphocytic and myelocytic leukemias. 

Presant and Bearman (1981) reported preliminary findings of a randomized trial that used isotretinoin either alone or in combination with busulfan for the treatment of patients with chronic phase chronic myelocytic leukemia. No differences have been noted in the time to development of blastic transformation in either group. The addition of the retinoid did not increase the acute toxicity of busulfan. Saccomanno et al. (1982) administered isotretinoin in 26 patients who exhibited varying degrees of cytologic atypia in exfoliated cells obtained from... 

---