Cancer treatment leukaemia

Ronghe, M., Burke, G.A., Lowis, S.R, and Estlin, E.J. 2001. Remission induction therapy for childhood acute lymphoblastic leukaemia clinical and cellular pharmacology of vincristine, corticosteroids, L-asparaginase and anthracyclines. Cancer Treatment Reviews 27(6), 327-337. 

Early worries about risk of cancer or leukaemia have proven unfounded in prolonged follow-up studies. However radioactive treatment is contraindicated in pregnant woman or nursing mothers. Other risks for the fetus are abortion, intrauterine death, congenital malformation and congenital hypothyroidism (if administered after 12 weeks gestation). It is customary to avoid pregnancy for the first... 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

L-Asparaginase, an enzyme derived from E. coli or Erwinia carotovora, has been employed in cancer chemotherapy where its selectivity depends upon the essential requirement of some tumours for the amino acid L-asparagine. Normal tissues do not require this amino acid and thus the enzyme is administered with the intention of depleting tumour cells of asparagine by converting it to aspartic acid and ammonia. Whilst L-asparaginase showed promise in a variety of experimentally induced tumours, it is only useful in humans for the treatment of acute lymphoblastic leukaemia, although it is sometimes used for myeloid leukaemia. 

Clinical trials have shown the recombinant interferons to be effective in the treatment of various cancer types, with rhIFN-a2a and -a2b both approved for treatment of hairy cell leukaemia. This is a rare B-lymphocyte neoplasm for which few effective treatments were previously available. Administration of the recombinant interferons promotes significant regression of the cancer in up to 90 per cent of patients. 

Further studies have shown additional cancer types, most notably ovarian and bladder cancer, non-Hodgkin s lymphoma and acute myeloid leukaemia, to be at least partially responsive to IL-2 treatment. However, a persistent feature of clinical investigations assessing IL-2 effects on various cancer types is variability of response. Several trials have yielded conflicting results, and no reliable predictor of clinical response is available. 

Humanized and chimerized MAbs have been developed for the treatment of non-Hodgkin lymphoma, renal cell carcinoma, ovarian carcinoma, breast cancer, melanoma, and neuroblastoma [117,119,120,123,124]. Patients with relapsed or refractory myeloid leukaemias that have been treated with HuM95, did not develop significant HAMA responses [59]. 

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. 

Weisberg E et al (2007) Second generation inhibitors of BCR-ABL for the treatment of ima-tinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 7 345-356... 

Alvocidib (flavopiridol, HMR 1275) 66 (Sanofi-Aventis) is being evaluated in Phase II/III trials for the treatment of chronic lymphocytic leukaemia in collaboration with Ohio State University and the US National Cancer Institute (NCI).124 Alvocidib 66 is also being evaluated in Phase I and II trials against... 

---