Imatinib administration in two patients with liver metastases from GIST and severe jaundice

Imatinib is the only effective and approved systemic therapy for the treatment of patients with advanced gastrointestinal stromal tumours (GISTs). Although metastases from GISTs most commonly involve the liver, yielding hyperbilirubinaemia, very few data on imatinib administration in subjects with jaundice are available. We provide evidence that imatinib tolerability was not adversely affected by jaundice in two patients with advanced GIST

Management of Skin Toxicity Related to the Use of Imatinib Mesylate (STI571, Glivec™) for Advanced Stage Gastrointestinal Stromal Tumours

Skin toxicity is a common side-effect of treatment with imatinib mesylate (STI571, Glivec™) in advanced gastrointestinal stromal tumours (GIST) and chronic myeloid leukaemia. The optimal duration of treatment with imatinib mesylate in GIST has not yet been established, as durable remissions have been observed in patients. It is, therefore, important to develop strategies to deal with common side-effects of what may be a long-term treatment. Here we report the case of a patient with advanced GIST who developed a cutaneous drug reaction secondary to imatinib mesylate and the various management options that may be employed depending upon the severity of the toxicity. The case and literature are discussed

Mesenteric gastrointestinal stromal tumour presenting as intracranial space occupying lesion

BACKGROUND: Gastrointestinal stromal tumours (GIST) usually present with non-specific gastrointestinal symptoms such as abdominal mass, pain, anorexia and bowel obstruction. METHODS: We report a case of a 42 year old male who presented with a solitary intracranial space occupying lesion which was established as a metastasis from a mesenteric tumour. RESULTS: The patient was initially treated as a metastatic sarcoma, but a lack of response to chemotherapy prompted testing for CD117 which returned positive. A diagnosis of mesenteric GIST presenting as solitary brain metastasis was made, and the patient was treated with imatinib. CONCLUSION: We recommend that all sarcomas with either an intraabdominal or unknown origin be routinely tested for CD117 to rule out GIST

Oral cancer treatment: developments in chemotherapy and beyond

Oncology is one of the few areas of medicine where most patients are treated intravenously rather than receiving oral drugs. Recently, several oral anti-cancer drugs have been approved and there are many more in development. Oral chemotherapy is attractive because of its convenience and ease of administration, particularly in the palliative setting. With an increasing number of oral agents emerging, we can expect to see a rapid rise in the use of oral chemotherapy in years to come. This article reviews recent developments in oral chemotherapy, both of traditional cytotoxics and novel, targeted agents, from the viewpoint of patients, physicians, drug developers and health-care providers

Targeted antitumour therapy – future perspectives

The advent of targeted therapy presents an unprecedented opportunity for advances in the treatment of cancer. A key challenge will be to translate the undoubted promise of targeted agents into tangible clinical benefits. Achieving this goal is likely to be dependent upon a number of factors. These include continued research to improve our understanding of the heterogeneity and complexity of the tumour microenvironment; refinement of clinical trial design to incorporate nontraditional end points such as the optimum biological dose and health-related quality of life; and the use of technological advancements in proteomics, genomics and biomarker development to better predict tumour types and patient subsets that may be particularly responsive to treatment, as well as enable a more accurate assessment of drug effect at the molecular level. In summary, the future success of targeted agents will require an integrated multidisciplinary approach involving all stakeholders

Gastrointestinal Stromal Tumours treated before and after the advent of c-kit immunostaining

<p>Abstract</p> <p>Background</p> <p>Recently developed immunohistochemical markers have revolutionised the classification of gastrointestinal stromal tumours (GISTs) whilst tyrosine kinase inhibitors (imatinib) have had a significant impact on the treatment of advanced tumours. We review the clinicopathological features of previously resected mesenchymal tumours of the gastrointestinal tract in our institution to 1) reclassify the histological diagnosis of those stained prior to c-kit availability; 2) perform survival analysis to identify prognostic factors, and 3) to consider the implications for patients.</p> <p>Methods</p> <p>Clinicopathological records of patients with a diagnosis of mesenchymal tumours treated between May 1992 and April 2007 were reviewed.</p> <p>Results</p> <p>82 patients were reviewed. 26 (32%) were reclassified as GISTs following c-kit immunostaining and a further 14 patients were treated for GIST up to April 2007 (Total: 40 patients; 21 males and 19 females, mean age 67, range 30-92 years). 36 (90%) underwent complete resection. 5-year survival of patients with GIST alone was 80%. Females had a better median survival (M: F 43 months: 73 months).</p> <p>Conclusions</p> <p>The availability of c-kit staining allowed 32% of previously diagnosed mesenchymal tumours to be reclassified as GISTs. This may have implications for the follow-up of patients diagnosed prior to the availability of this method.</p

Combination of RAD001 (everolimus) and docetaxel reduces prostate and breast cancer cell VEGF production and tumour vascularisation independently of sphingosine-kinase-1

Resistance to docetaxel is a key problem in current prostate and breast cancer management. We have recently discovered a new molecular mechanism of prostate cancer docetaxel chemoresistance mediated by the mammalian target of rapamycin (mTOR)/sphingosine-kinase-1 (SK1) pathway. Here we investigated the influence of this pathway on vascular endothelial growth factor (VEGF) production and tumour vascularisation in hormone resistant prostate and breast cancer models. Immunofluorescent staining of tumour sections from human oestrogen receptor (ER)-negative breast cancer patients showed a strong correlation between phosphorylated P70S6 kinase (mTOR downstream target), VEGF and SK1 protein expression. In hormone-insensitive prostate (PC3) and breast (MDA-MB-231 and BT-549) cancer cell lines the mTOR inhibitor RAD001 (everolimus) has significantly inhibited SK1 and VEGF expression, while low dose (5 nM) docetaxel had no significant effect. In these cell lines, SK1 overexpression slightly increased the basal levels of VEGF, but did not block the inhibitory effect of RAD001 on VEGF. In a human prostate xenograft model established in nude mice, RAD001 alone or in combination with docetaxel has suppressed tumour growth, VEGF expression and decreased tumour vasculature. Overall, our data demonstrate a new mechanism of an independent regulation of SK1 and VEGF by mTOR in hormone-insensitive prostate and breast cancers

Secondary fibrosarcoma of the brain stem treated with cyclophosphamide and Imatinib

Radiation-induced midbrain fibrosarcoma is a rare, highly aggressive tumor, which is associated with poor prognosis. We present the case of a 48-year old man with brainstem fibrosarcoma 20 years following radiation therapy received for a pituitary tumor. We discuss this case in the context of the diagnostic criteria for these tumors, and previous reports of secondary and primary sarcomas of the central nervous system