The patient gave his full and informed consent to initiate therapy with this medi cation and was fully aware that http://www.selleckchem.com/products/Calcitriol-(Rocaltrol).html adenocarcinoma of the tongue is not an approved indication for sunitinib. The drug was administered using standard dosing at 50 mg, orally, every day for 4 weeks followed by a planned 2 weeks off of the drug. After 28 days on sunitinib and 12 days off the patient had a PET CT scan and this was compared to the baseline pretreatment scan. Using Response Evaluation Criteria in Solid Tumors criteria, the lung metastases Inhibitors,Modulators,Libraries had decreased in size by 22% and no new lesions had appeared. This was in contrast to the 16% growth seen in the previous month prior to initiation of sunitinib and the growth while on erlotinib. Because of typical side effects, his dose of sunitinib was reduced to 37.
5 mg daily for 4 weeks out of 6. Repeated scanning Inhibitors,Modulators,Libraries continued to show disease stabilization and the absence of new tumor nodules for 5 months. Cancer recurrence After 4 months on sunitinib, the patients CT scan showed evidence of growth in the lung metastases. He was then switched to sorafenib and sulindac, as these were medications that were also thought to be of poten tial benefit given his initial genomic Inhibitors,Modulators,Libraries profiling. Within 4 weeks a CT scan showed disease stabilization and he continued on these agents for a total of 3 months when he began to develop symp toms of disease progression. At this point he was noted to have developed Inhibitors,Modulators,Libraries recurrent disease at his primary site on the tongue, a rapidly growing skin nodule in the neck, and progressive and new lung metastases.
A tumor sample was removed from the metastatic skin nodule and was subjected to both WTSS and genomic sequencing. There were 1,262,856,802 and 5,022,407,108 50 bp reads that were aligned from the transcriptome and genomic DNA, respectively. Nine new non synon ymous protein coding changes were detected that were not present within either the pre treatment tumor or the Inhibitors,Modulators,Libraries normal DNA in addition to the four somatic changes determined in the pre treatment tumor. Reexamination of the sequence reads from the initial tumor analysis did not reveal the presence of any of these nine new mutated alleles even at the single read level. Extensive copy number variations were also observed in the post treatment sample not present before treatment, including the arising of copy number neutral regions of LOH on chromosomes 4, 7 and 11.
In the tumor recurrence, 0. 13% meanwhile of the gen ome displayed high levels of amplification, compared to 0. 05% in the initial tumor sample. Also, 24. 8% of the initial tumor showed a copy number loss whereas 28. 8% of the tumor recur rence showed such a loss. We identified eight regions where the copy number sta tus changed from a loss to a gain in the tumor recur rence and twelve regions where the copy number changed from a gain to a loss. Indicative of heterogeneity in the tumor sample, the initial tumor showed 18.