Melanoma, colorectal

Lung cancer Breast cancer Melanoma Colorectal cancer Hematologic malignancies (i.e., leukemia)... 

Patients with other types of unresectable cancer also may benefit from chemotherapy, as evidenced by prolongation of life, shrinkage of tumor, and improvement in symptoms. Notable among these are ovarian epithelial and breast carcinomas, oat cell (small cell undifferentiated) carcinoma of the lung, and acute myelocytic leukemia. Cancers that are for the most part resistant to today s agents include melanoma, colorectal and renal carcinomas, and non-oat cell cancers of the lung. 

CNS tumors, Hodgkin s disease, lymphomas, melanoma, colorectal and renal cell... 

Finally, biological response modifiers should be mentioned. Immunostimulants, a concept predating this century, are making a modern-day comeback with intensive research of interferons, interleukin, and synthetic polynucleotides. Studies involving interleukin-2 described significant responses in patients with melanoma, colorectal, kidney, and lung cancers. This and other stimulant factors are now in clinical use (see Chapter 15). 

Melanoma, colorectal carcinoma, prostate cancer, rheumatoid arthritis, psoriasis... 

Ras, a historical proto-oncogene, is frequently mutated in many human cancers, including 90% of pancreatic cancers, 50% of colorectal cancers, 30% of lung cancers, and 15-30% of melanomas [10-12]. There are three Ras genes that encode four family members K-Ras (two alternatively spliced isoforms), H-Ras, and N-Ras. Mutations are most commonly found in K-Ras [13]. These mutations result in impaired GTP hydrolysis, which shifts the equilibrium toward GTP-bound active Ras, and results in constitutive intracellular signaling. 

In precHnical models, ARRY-142886 treatment results in either tumor regression or stasis in xenograft models of colorectal, non-small cell lung, pancreatic, breast, and melanoma cancers. Most of these cell lines contain either the B-Raf or K-Ras mutations. Complete inhibition of pERKl/2 formation in excised tumors from both HT-29 and BxPC3 studies was achieved 4 h after an oral dose of 20 mg/kg/day ARRY-142886 [114]. In a separate HT-29 study, a PK/PD relationship was established [115]. Twelve hours after a single 30 mg/kg oral dose of ARRY-142886, approximately 80% inhibition of ERKl/2 phosphorylation was observed with a corresponding plasma concentration of about 0.60 xg/ml. In the same study at 24 h, ERKl/2 phosphorylation was... 

In November 2005, a phase II/III study in NSCLC patients started in Australia and Canada, hi February 2006, Cediranib was undergoing a UK phase II/III trials in colorectal cancer. At that time, US phase II trials were underway in patients with advanced solid tumors, mesothelioma, melanoma, fiver, ovarian, peritoneal, fallopian tube, kidney, and breast cancers, hi May 2006, a US phase II trial began for neurofibromatosis type I and plexiform neurofibroma. 

Carmustine and lomustine can produce remissions that last from 3 to 6 months in 40 to 50% of patients with primary brain tumors. Both drugs also are used as secondary treatment of Hodgkin s disease and in experimental combination chemotherapy for various types of lung cancer. Other tumors in which remission rates of 10 to 30% have been obtained are non-Hodgkin s lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and colorectal cancer. 

H. Other considerations Interferon alfa-2a has been designated an orphan drug product for the treatment of chronic myelogenous leukemia, AIDS-related Kaposi s sarcoma, renal cell carcinoma, metastatic malignant melanoma, and esophageal and colorectal cancer. 

IL-2 has been approved for the heatment of renal cell carcinoma and also has shown good activity in malignant melanoma. Both of these tumors are refractory to chemotherapy. IL-2 has also been used invesdgationally, both alone and in combinadon with LAK cells, with chemotherapy and with other biological response modifier s (BRM s) to d eat a variety of different cancers (e.g., head and neck carcinoma, colorectal cancer, cend al nervous system cancer etc). In addidon to cancer therapy, IL-2 has been used to d eat padents infected with human immunodeficiency virus and it has been used ex vivo to generate antiviral T cells which were reinfused into padents (Lewko and Oldham, 2003 Dorr, 1993). 

Morbidity should not exceed 30%. Lethality is between 0-3%. The 5-year survival rate following RO resection in metastatic colorectal carcinoma is 20-40%, in neuroendocrine tumours 90-100%, in malignant melanoma 15-25%, and in breast cancer 10-30%. Prognosis is poor in metastasizing renal cell carcinoma and in gastric or pancreatic carcinoma. Both R1 and R2 resection worsen the prognosis to the same extent. 

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