Doxorubicin lymphomas

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

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... 

LL, a 47-year-old man, was diagnosed with high-risk diffuse large cell B-cell non-Hodgkin s lymphoma (NHL) 12 months ago. LL had a complete response to his initial treatment of six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). LL is participating in a clinical trial and is randomized to receive a myeloablative autologous HCT TBI days 8 to 5, etoposide day 4, rest day 3, cyclophosphamide day 2, rest day 1, with infusion of autologous PBPC on day 0. 

Sapra P, Moase EH, Ma J, et al. Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab fragments. Clin Cancer Res 2004 10 1100. 

Tsavaris N, Kosmas C, Vadiaka M, et al. Pegylated liposomal doxorubicin in the CHOP regimen for older patients with aggressive (stage III/V) non-Hodgkin s lymphoma. Anticancer Res 2002 22 1845. 

Anthracyclines Doxorubicin/ adriamycin Melanoma, Ovarian carcinoma, T-cell lymphoma, Colon carcinoma, B-cell lymphoma, Various disseminated refractory malignandes, Breast cancer, Lung cancer, Pancreatic cancer, Liver cancer, Neuroblastoma... 

In addition, combination therapy trials of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in refractory and newly diagnosed patients suggests that rituximab may also have a role in the eradication of residual disease. This combination appears to be a viable treatment option for relapsed low-grade non-Hodgkin lymphoma... 

Doxorubicin and dannorabicin are antibiotics made from microorganisms of the family Streptomyces peucetius. The stmcture of these anthracyclines contains an aminosaccarhide residue daunozamine attached to a naphthacenequinone nucleus. Doxorubicin differs from daunorubicin in the presence of a hydroxyl gronp at C14. A nnmber of mechanisms have been suggested in which anthracyclines exhibit cytotoxicity. They canse DNA to denature, are involved in oxidation-rednction reactions, chelate bivalent cations and react with cell membranes, changing their fnnction. They are used for severe leukemia, lymphoma, breast and ovarian cancer, and other solid tumors. 

Doxorubicin is one of the most effective agents used in the treatment of carcinomas of the breast, ovary, endometrium, bladder, and thyroid and in oat cell cancer of the lung. It is included in several combination regimens for diffuse lymphomas and Hodgkin s disease. Doxorubicin can be used as an alternative to daunorubicin in acute leukemias and is useful in Ewing s sarcoma, osteogenic sarcoma, soft-tissue sarcomas, and neuroblastoma. Some activity has been reported in non-oat cell lung cancer, multiple myeloma, and adenocarcinomas of the stomach, prostate, and testis. 

Mitoxantrone is active against breast carcinomas, leukemias, and lymphomas. Its antitumor efficacy in patients with breast cancer is slightly lower than that of doxorubicin. Its major toxicity is myelosuppression mucositis and diarrhea also may occur. Mitoxantrone produces less nausea, alopecia, and cardiac toxicity than does doxorubicin. 

Epirubicin (FARMORUBICIN) is structurally similar to doxorubicin and is similarly effective in the treatment of breast cancer, lung cancer and lymphoma. 

Lopes de Menezes, D.E., L.M. PUarski, and T.M. Allen, In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. Cancer Res, 1998. 58(15) 3320-30. 

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

Doxorubicin Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks inhibits topoisomerase II intercalates into DNA Breast cancer, Hodgkin s and non-Hodgkin s lymphoma, soft tissue sarcoma, ovarian cancer, non-small cell and small cell lung cancer, thyroid cancer, Wilms tumor, neuroblastoma Nausea, red urine (not hematuria) Cardiotoxicity (see text), alopecia, myelosuppression, stomatitis... 

Sirolimus has also been used in the production of sirolimus-eluting stents. These stents are used to treat obstructive coronary arteries. The rationale for the use of sirolimus in these stents is due to its antiproliferative activity. It has also received attention for cancer treatment due to its antiproliferative effects. In animal studies, sirolimus has shown some potential in the treatment of cancer where in combination with doxorubicin, a remission for Akt-positive lymphomas has been observed. 

Doxorubicin Adriamycin RDF, Rubex, others Acute leukemias carcinoma of bladder, breast, ovary, thyroid, and other tissues Hodgkin disease non-Hodgkin lymphomas several sarcomas Similar to daunorubicin... 

CHOP Cyclophosphamide (Cytoxan), doxorubicin, vincristine (Oncovin), prednisone Non-Hodgkin lymphoma... 

Cyclophosphamide (Cytoxan and Endoxan) is used in the treatment of Hodgkin s disease, lymphosarcoma, and other lymphomas. It is employed as a secondary drug in patients with acute leukemia and in combination with doxorubicin in women with breast cancer. A drug combination effective in the treatment of breast cancer is cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP). Cyclophosphamide is also an immunosuppressive agent. The toxicity of cyclophosphamide causes alopecia, bone marrow depression, nausea and vomiting, and hemorrhagic cystitis. 

Diffuse histiocytic lymphoma Cyclophosphamide, Adriamycin (doxorubicin), vincristine, and prednisone (CHOP) bleomycin, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), and prednisone (BACOP) or cyclophosphamide, Oncovin (vincristine), methotrexate, and cytarabine (COMA). 

S. Basu, B. Mukhopadhyay, S.K. Basu and A. Mukhopadhyay, Enhanced intracellular delivery of doxorubicin by scavenger receptor-mediated endocytosis for preferential killing of histiocytic lymphoma cells in culture, FEBS Lett 342 (1994) 249-254. 

Non-Hodgkin s lymphoma Combination chemotherapy cyclophosphamide, doxorubicin, vincristine, prednisone Bleomycin, lomustine, carmustine, etoposide, interferon, mitoxantrone, ifosfamide, rituximab... 

Combination chemotherapy is the treatment standard for patients with diffuse non-Hodgkin s lymphoma. The anthracycline-containing regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been considered the best treatment in terms of initial therapy. Recently, randomized phase III clinical studies have shown that the combination of CHOP with the anti-CD20 monoclonal antibody rituximab results in improved response rates, disease-free survival, and overall survival compared with CHOP chemotherapy alone. 

To further support the use of a 6-mg fixed dose of pegfilgrastim, a Phase II study was conducted in 29 patients with non-Hodgkirfs lymphoma who received a single SC 6-mg dose of pegfilgrastim approximately 24 h after the start of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy [42]. No relationship between the duration of grade 4 neutropenia and body weight was seen, and no unexpected adverse events were reported. 

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. 

Allen,T. M., Mumbengegwi, D. R.,and Charrois, J. R. (2005), Anti-CD19-targeted doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates, Clin. Cancer Res., 11, 3567-3573. 

Available data suggest that the antitumor therapeutic response of older patients is optimal when exposure to appropriate chemotherapy is the same as for younger patients. For example, the treatment of non-HodgkiiVs lymphoma with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or etoposide, mitoxantrone, and prednimustine (VMP) is less effective in older patients when dose reductions are made (73, 74). Similarly, treatment of metastatic breast cancer in younger and older patients with the same dose intensity of doxorubicin-based chemotherapy resulted in similar outcomes as measured by time to progression of disease and overall survival (75). 

Diffuse large-cell lymphoma CHOP cyclophosphamide + doxorubicin + vincristine (Oncovin) - prednisolone... 

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