Vincristine Hodgkin

The observation that fractions of the rosey periwinkle, Catharanthus rosea, produced severe leukopenia, resulted in the isolation and development of two major anticancer drugs, vincristine and vinblastine. These two complex, dimeric indole-indoline alkaloids are important in the treatment of acute childhood leukemia (vincristine), Hodgkin s disease (vinblastine), and metastatic testicular tumors (vinblastine), and continue to be manufactured today by mass cultivation and processing of their natural source. 

Vincristine and Vinblastine (CCS) i Microtubular polymerization—spindle poisons (M phase) Vinblastine—Hodgkin s (ABVD), testicular CA, Kaposi s vincristine—Hodgkin s (MOPP), leukemias, Wilms BMS, GI, alopecia Neurotoxicity... 

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). 

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. 

Researchers from Eli Lilly pharmaceuticals, (a company founded in 1876 by Colonel Eli Lilly veteran of the US Civil War), undertook further intensive phytochemical studies and characterized 60 alkaloids, of which a group of 20 binary indole alkaloids—including vincristine and vinblastine. Vinblastine sulphate (Velbe ) inhibits the polymerization of tubulin and is used to treat generalized Hodgkin s disease and chorionepithelioma, whereas vincristine sulphate (Oncovin ) is used to treat leukemia in children. 

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... 

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... 

Vincamine, vinblastine and vincristine are very important clinic alkaloids. They are produced naturally by plants vincamine by Vinca minor, and vinblascine and vincristine by Madagascar periwinkle Catharanthus roseus). The vindoline synthesis pathway starts with strictosidine and, via dehydrogeissoschizine, preakuammicine, stemmadenine and tabersonine, is converted to vindoline and vincristine (Figure 42). Conversion from vindoline to vinblastine is based on the NADH enzyme activity. Vinblastine and vincristine are very similar alkaloids. The difference is that vincristine has CHO connected to N, whereas vinblastine in the same situation has only CO3. This synthetic structural differences influence their activity. Vinblastine is used to treat Hodgkin s disease (a form of lymphoid cancer), while vincristine is used clinically in the treatment of children s leukaemia. Vincristine is more neurotoxic than vinblastine. 

Alkaloids such as vinblastine and vincristine are known to bind to the microtubules of the spindle apparatus. They are active agents that influence DNA synthesis and amino acid metabolism. They are also known to reduce mitosis at metaphase. Vinblastine and vincristine also have some immunosuppressive activity. There are many applications of these alkaloids. They have been used in the treatment of Hodgkin s disease, cancers and blood disorders. Vincristine is a basis for the development of clinic agents used to treat cerebral and pulmonary disorders. Vinblastine and vincristine are well-known anficancer agents. 

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%. 

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. 

Catharanthus roseus (L.) G. Don Chang Chun Hua (Madagascar periwinkle) (whole plant) Vinblastine, vincristine, carosine, vinrosidine, lenrosine, lenrosivine, rovidine, perivine, perividine, vindolinine, pericalline.33 This herb is toxic. Anticancer in chronic lymphocytic leukemia and Hodgkin s disease, in acute lymphocytic leukemia. 

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... 

MOPP Mechlorethamine (Mustargen), vincristine (Oncovin), procarbazine, prednisone Hodgkin Disease... 

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. 

Hodgkin s disease Mechlorethamine, Oncovin (vincristine), procarbazine, and prednisone (MOPP). 

Procarbazine (Matulane) inhibits DNA, RNA, and protein synthesis through an unknown mechanism. It is effective in patients with Hodgkin s disease when given in combination with mechlore-thamine, vincristine, and prednisone (MOPP). Procarbazine causes neurotoxicity, bone marrow... 

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

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