Vincristine lymphomas

Nitrogen mustard is clinically used for the treatment of lymphomas and some forms of lung cancer. The major indication for mechlorethamine is Hodgkin s disease as a part of the MOPP regimen (mechlorethamine + vincristine (oncovin) + procarbazine + prednisone). The usual dose consists of 6 mg/m2 on days 1 and 8. This drug has pronounced hematological toxicity (myelo-suppression). 

Vinblastine is another vesicant vinca alkaloid that causes myelo-suppression and less neurotoxicity than vincristine. The pharmacokinetics of vinblastine are best described by a three-compartment model, with an a half-life of 25 minutes, a 3 half-life of 53 minutes, and a terminal half-life of 19 to 25 hours.12 Vinblastine has shown activity in the treatment of bladder, breast, and kidney cancer, as well as some lymphomas. The doses of vinblastine tend to be higher on a milligram per meter squared basis than vincristine. Nausea and vomiting are minimal with vinblastine. Other side effects include mild alopecia, rash, photosensitivity, and stomatitis. 

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. 

The Phase I studies of vindesine determined the maximum tolerated dose of the compound to be 3-4 mg/m (body surface area) when given once weekly (i.v.) 78). Mild leukopenia ensues, reaching a nadir after about 4 days, and is accompanied by neurotoxicity. Several patients responded to drug treatment during this initial trial, including several complete responders with acute leukemias and partial responders with malignant melanoma and non-Hodgkin s lymphoma. Subsequent studies indicated that vindesine was active in vincristine-resistant childhood lymphocytic leukemia and, when combined with cisplatin, was effective in... 

MACOP-B Methotrexate, daunomycin, cyclophosphamide, vincristine, prednisone, bleomycin Lymphoma... 

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... 

Vinblastine and vincristine differ only in the substituent on the nitrogen atom of the indol fragment of the molecule, and are used in combination with other chemotherapeutic agents. They are mainly used for leukoses, myelomas, sarcomas, cancer of various organs, and for lymphomas. 

The major indication for mechlorethamine is Hodgkin s disease the drug is given in the MOPP regimen (mechlorethamine, vincristine, procarbazine, prednisone see Chapter 55). Other less reactive nitrogen mustards are now preferred for the treatment of non-Hodgkin s lymphomas, leukemias, and various solid tumors. 

The best known drugs acting as antimitotics are the vinca alkaloids, vincristine (7.90) and vinblastine (7.91). They are very complex indole derivatives that nevertheless have been synthesized. Both are quite effective in various leukemias and in Hodgkin s lymphoma, but show considerable neurotoxicity. Vinblastine and vincristine bind specifically to the microtubular protein tubulin in dimeric form, precipitating depolymerization of the microtubules and functionally acting as a mitotic poison. Vinorelbine (7.92) is a semisynthetic vinca alkaloid functionally identical to vinblastine. 

Vincristine Inhibits mitosis ALL, Hodgkin s and non-Hodgkin s lymphoma, rhabdomyosarcoma, neuroblastoma, Wilms tumor None Neurotoxicity with peripheral neuropathy, paralytic ileus, myelosuppression, alopecia, SIADH... 

Vincristine has been effectively combined with prednisone for remission induction in acute lymphoblastic leukemia in children. It is also active in various hematologicmalignancies such as Hodgkin s and non-Hodgkin s lymphomas, and multiple myeloma, and in several pediatric tumors including rhabdomyosarcoma, neuroblastoma, Ewing s sarcoma, and Wilms tumor. 

Asian patients have been proposed to be at higher risk of SIADH during treatment with vincristine. Between 1983 and 1999, 76 cases of hyponatremia and/or SIADH related to the use of vincristine were reported to the global adverse event database of Eli Lilly and Company. The average age of the patients was 36 years (range 2 weeks to 86 years) and 62% were male. Most of the patients had received vincristine for leukemia or lymphomas. Of the 76 reports, 39 included background information on race 35 patients were Asian, three were Caucasian, and one was black. The authors concluded that there may be a correlation between race and vinca alkaloid-associated SIADH/hyponatremia however, the reasons are still unclear (1198). 

Vincristine Oncovin, Vincasar Acute lymphocytic leukemia neuroblastoma Wilms tumor Hodgkin disease non-Hodgkin lymphomas Ewing sarcoma Neurotoxicity [peripheral neuropathies, CNS disorders] hair loss local irritation at injection site... 

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

This is present in mechlorethamine (Mustargen), which is used in patients with Hodgkin s disease and other lymphomas, usually in combination with other drugs, such as in MOPP therapy (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone). It may cause bone marrow depression. 

Diffuse histiocytic lymphoma Cyclophosphamide, vincristine, methotrexate, and cytarabine (COMA). 

Nodular lymphoma Cyclophosphamide, Oncovin (vincristine), and prednisone (CVP). 

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). 

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. 

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