Doxorubicin Hodgkin

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. 

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. 

JM is a 32-year-old woman who was recently diagnosed with stage IIIB Hodgkin s disease. She comes to the clinic to receive her first dose of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy. She currently does not have a central access device therefore, she will receive her chemotherapy via peripheral vein. 

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. 

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 1974 Osteogenic sarcoma, Hodgkin s disease, CML, soft tissue sarcoma Inhibitor of DNA replication, transcription, repair [20]... 

Doxorubicin (Adriamycin, Rubex) [Antineoplastic/ Anthrocycline Antibiotic] Uses Acute leukemias Hodgkin Dz NHLs soft tissue, osteo Ewing sarcoma Wilms tumor neuroblastoma bladder, breast, ovarian, gastric, thyroid, lung CA Action Intercalates DNA X DNA topoisomerases I II Dose 60-75 mg/m q3wk X w/ hqjatic impair IV use only X... 

The chemotherapy of advanced Hodgkin s disease is one of the best examples of successful combination chemotherapy. Combination therapy with the MOPP regimen (mechlorethamine, Oncovin [vincristine sulfate], procarbazine, prednisone), alternating with ABVD (Adriamycin [doxorubicin hydrochloride], bleomycin, vinblastine, dacarbazine), has resulted in cure rates of 50 to 60%. 

Dacarbazine is the most active agent used in metastatic melanoma, producing a 20% remission rate. It is also combined with doxorubicin and other agents in the treatment of various sarcomas and Hodgkin s disease. 

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. 

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... 

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... 

Chemotherapeutic Regimen ABVD Components of Regimen Doxorubicin (Adriamycin), bleomycin (Blenoxane), vinblastine (Velban), dacarbazine (DTIC) Primary Indication Hodgkin Disease... 

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. 

Hodgkin s disease (stages III and IV) Combination chemotherapy vinblastine, doxorubicin, dacarbazine, bleomycin Lomustine, etoposide, ifosfamide, interferon, mechlorethamine, vincristine, procarbazine, prednisone... 

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. 

These compounds illustrate the structural diversity of carbohydrates. Glucose is the most common simple sugar, whereas cellulose, which comprises wood, piant stems, and grass, is the most common carbohydrate in the piant world. Doxorubicin, an anticancer drug that has a carbohydrate ring as part of its structure, has been used in the treatment of ieukemia, Hodgkin s disease, and cancers of the breast, biadder, and ovaries. 2 -Deoxyadenosine 5 -monophosphate is one of the four nucieotides that form DNA. 

Hodgkin s disease MOPP mustine (chlormcthine) + vincristine + procarbazine + prednisolone ABVD doxorubicin (Adriamycin) + bleomycin + vinblastine + dacarbazine... 

Bleomycin is a cytostatic drug that causes double-strand breaks in DNA. It has been used to treat Hodgkin s disease and a variety of solid cancers. It is often used in combination with other anticancer drugs, for example in the regimens known as ABVD (doxorubicin -r bleomycin -r vinblastine-r dacarbazine) and BEP (bleomycin-r etoposide -r cisplatin). It has also been injected intrapleu-rally in the management of malignant effusions. 

Five of thirty-two patients treated with the alternating drug regimen CAMBO-VIP (cyclophosphamide, doxorubicin, methotrexate, bleomycin, vincristine, etoposide, ifosfamide, and prednisolone) for non-Hodgkin s lymphoma developed blisters under the thickened skin of the palms and/or soles, followed by desquamation (28). 

Acute febrile interstitial pneumonitis occurred within less than 48 hours after the second to fourth cycles of chemotherapy (doxorubicin, cyclophosphamide, bleomycin, methotrexate, plus methylprednisolone) in five patients with non-Hodgkin s lymphoma who were receiving prophylactic G-CSF n — 3) or GM-CSF (n = 2) (23). Lymphocytic alveolitis was confirmed in four of these patients and all three patients tested had an increased number of CD8+ T cells. Even though all the patients received high-dose methylprednisolone, two died as a result of diffuse and extensive interstitial pulmonary fibrosis, demonstrated at postmortem. Although both G-CSF and GM-CSF can cause acute pneumonitis in patients with cancers, it is still unknown to what extent hemopoietic growth factors are involved in this complication. 

A 55-year-old man with chronic lymphocytic leukemia and rheumatoid arthritis took methotrexate for 4 years and developed a B cell non-Hodgkin s lymphoma in the shoulder and axillary lymph nodes he had Epstein-Barr viral antigens in the serum. After radiation and chemotherapy had failed, complete remission was achieved with a combination of rituximab and EPOCH (etoposide -I- prednisone -I- vincristine -I-cyclophosphamide + doxorubicin). 

Procarbazine is an alkylating agent that is used in the treatment of Hodgkin s disease in regimens such as MOPP (chlormethine (mechlorethamine), vincristine (Oncovin), procarbazine, and prednisolone) and BEACOPP (bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine, procarbazine, and prednisone) (1). It is also used to treat glioblastoma multiforme. 

In 37 patients with HIV-associated non-Hodgkin s lymphoma who were treated with a 96-hour continuous intravenous infusion of cyclophosphamide + doxorubicin + etoposide, severe (grade 3 or 4) mucositis occurred in eight of 12 patients who received concomitant saquinavir (600 mg tds) compared with three of 25 who did not receive saquinavir. Although the authors did not measure saquinavir plasma concentrations, they suggested that this finding may have been explained by inhibition of the metabolism of one or more of the cytotoxic drugs by saquinavir (17). 

AR is a 48-year-old woman who was treated for Hodgkin s disease 15 years ago with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). She now presents with breast cancer and her oncologist feels that chemotherapy with FAC (fluorouracil, doxorubicin [Adriamycin], and cyclophosphamide) is the most appropriate regimen. Her previous chemotherapy included a total of 300 mg/m doxorubicin exposure. Which of the following agents may be utilized to reduce risk of cardiotoxicity associated with the anthracycline therapy she is about to receive ... 

In the last 2-5 years, selected monoclonal antibodies have become a routine part of care for certain malignancies. Rituximab, a chimeric monoclonal antibody used against CD 20 positive B-cell non-Hodgkin s lymphoma, is now utilized in combination with the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone). Trastuzu-mab, a humanized monoclonal antibody, is a weekly maintenance therapy for HER2neu-positive metastatic breast cancer patients. 

CDE cyclophosphamide, doxorubicin, and etoposide cHL classical Hodgkin s lymphoma... 

Press OW, LeBlanc M, Lichter AS, et al. Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage lA to IIA Hodgkin s disease. J ain Oncol 2001 19 4238M244. 

Doxorubicin . Intercalator, forms free radicals, inhibits topoisomerase Hodgkin s (ABVD), breast, endometrial, lung, ovarian CA BMS—delayed CHF (dexrazoxane is an iron-chelating agent preventing the formation of free radicals it is not a free radical trapper ), alopecia, vesicant, radiation recall ... 

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