Doxorubicin conventional

DOXORUBICIN, CONVENTIONAL (Adriamycin RDF preservative-free solution for injection 2 mg/mL)... 

There are certain histologic subtypes of diffuse, aggressive NHL that respond less well to treatment with conventional regimens such as CHOP. Burkitt s lymphoma, lymphoblastic lymphoma, mantel cell lymphoma, and primary CNS lymphoma are examples of disease that benefit from more intensive therapy. Regimens such as hyper-CVAD, which alternate cycles of hyperfractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone with high-dose cytarabine and methotrexate, often are substituted for CHOP. Intrathecal therapy with methotrexate is indicated with documented CNS infiltration of tumor or involvement of the sinuses. The recent appreciation of the etiology of Helicobacter pylori in the etiology of peptic ulcer disease and the association between colonization and mucosal-associated lymphoma (MALT) has spurred... 

Table 23.1 details all of the recent Food and Drug Administration (FDA)-approved agents. In this section we will detail some interesting aspects of the approach to their development. As can be seen in Table 23.1 there are 21 new entities. Of note is that only seven (33%) of the agents including capecitabine, liposomal doxorubicin, temozolomide, and oxaliplatin, ABl-007, liposomal cytarabine, and pemetrexed could be considered conventional cytotoxic... 

Batist, G., Ramakrishnan, G., and Rao, C. S. (2001), Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer,/. Clin. Oncol., 19,1444-1454. 

An interaction of doxorubicin with the anti-HER2 receptor humanized monoclonal antibody, trastuzumab (Herceptin), has been reported. Most patients who received trastuzumab in early trials had been pretreated with anthracyclines. Despite this, preliminary information suggested that reduced systolic cardiac function was an adverse effect of trastuzumab (119). More recently, this problem has been further highlighted in a study of women with metastatic breast cancer (120). Patients who had not received prior anthracycline-containing adjuvant chemotherapy were at greater risk of cardiotoxicity when they received trastuzumab in combination with doxorubicin or cyclophosphamide (27 and 75% respectively), compared with only 11% of patients who received trastuzumab in combination with pachtaxel (120,121). The risk of cardiac events in patients treated with doxorubicin, cyclophosphamide, and trastuzumab increased markedly after a cumulative doxorubicin dose of 360 mg/m. This suggests synergistic cardiotoxicity with trastuzumab and doxorubicin. Trastuzumab is therefore currently licensed only for use in conjunction with pacli-taxel or docetaxel and not with conventional doxorubicin. 

Liposomal doxorubicin in Myocet has systemic avail-abihty, metabolism, and excretion similar to that of conventional doxorubicin, but at a slower rate (8). In dogs, the plasma concentrations of doxorubicin from Myocet were 1000-fold greater than conventional doxorubicin at 6 hours, but the difference diminished at 24 hours (9). This distinguishes Myocet from DoxU, which persists in the circulation for significantly longer. 

High-dose Myocet (135 mg/m ) caused significant hematological toxicity, namely grade 4 neutropenia in 98% and thrombocytopenia in 46 of 52 patients (21). However, Myocet 75 mg/m 3-weekly caused less hematological toxicity than conventional doxorubicin (20). 

Myocet (75 mg/m ) causes significantly less vomiting (11 versus 23%) than conventional free doxorubicin (75 mg/m ) (20). It also leads to lower peak-free doxorubicin... 

Unlike extravasation of conventional doxorubicin, which can cause severe local inflammation and tissue damage, extravasation of hposomal doxorubicin was associated with only mild transient irritation at the infusion site in the eight documented cases (34,35). 

Harris L, Batist G, Belt R, Rovira D, Navari R, Azarnia N, Welles L, Winer E TLC D-99 Study Group. Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer 2002 94(l) 25-36. 

Liposomes are lipid-based vesicles useful in delivering conventional as well as macromolecular therapeutic agents (35). The commercially available liposomal formulations include Doxil (doxorubicin) and Ambisome (amphotericin B), which are available for the treatment of tumors and fungal infections, respectively. Egg yolk and soy lecithins that are mainly composed of phospholipids (< 95%) are commonly used as raw materials for liposome preparation. Of the two, soy lecithins are generally preferred for reasons of... 

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