Onkologie最新文献

Background: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors.

Methods: The patients received cisplatin 30 mg/m² and irinotecan 50 mg/m² weekly from week 1 to week 4, with SU5416 at either 65 mg/m² (dose level (DL)1) or 85 mg/m² (DL2) twice weekly for 6 weeks (1 cycle). Serial ¹⁸fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) and ¹⁵O-H₂O-PET scans were obtained.

Results: 13 patients were treated (7 on DL1, 6 on DL2); 7 patients completed at least 1 cycle of treatment. 3 patients experienced dose-limiting toxicity (DLT) at DL2 (grade 3 neutropenia and grade 3 thrombocytopenia causing treatment delay, grade 3 nausea/vomiting). No objective responses were observed at DL1, which was determined to be the maximum tolerated dose (MTD). 1 partial response (PR) was observed at DL2. ¹⁸FDG-PET responses were documented but did not predict response according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Conclusions: SU5416 at 65 mg/m² twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity. ¹⁸FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development.

Background: Although depression is often reported in prostate cancer patients, some tests of depression omit the somatic criteria that are listed for Major Depressive Episode, arguing that these may be confounded by the cancer itself. However, this omission may be challenged in terms of the particular somatic symptoms that have been associated with prostate cancer. Therefore, the present study investigated the relative contribution to total depression scores made by the somatic criteria for Major Depressive Episode that were not caused by prostate cancer.

Patients and methods: 491 prostate cancer patients completed the Zung Self-Rating Depression Scale. Data were analysed to compare the predictive power of 5 subsets of depression on patients' total depressive scores.

Results: Somatic symptoms were the most powerful predictor of total depression scores, followed by anhedonia and depressed mood, with similar findings for depression clinical status. Emotional symptoms and cognitive confusion were not significant predictors of total depression scores but did predict depression clinical status.

Conclusion: Valid and reliable assessment of depression and selection of appropriate treatment options in prostate cancer patients requires consideration of somatic items which match the DSM-IV-TR criteria for Major Depressive Episode.

Background: The aim of this study was to investigate the relationship between the expression of hypoxia-inducible factor-1α (HIF-1α), Ras-related C3 botulinum toxin substrate 1 (Rac1), and vascular endothelial growth factor (VEGF), as well as their correlation with angiogenesis and prognosis in gastric carcinoma.

Material and methods: The expression of Rac1, HIF-1α, VEGF, and CD34 (described in terms of microvessel density, MVD) was determined by immunohistochemical staining of tissues from 60 radically resected gastric cancer specimens.

Results: The proportion of specimens expressing Rac1, HIF-1α, and VEGF was 37/60 (61.7%), 35/60 (58.3%), and 40/60 (66.7%), respectively. The levels of Rac1, HIF-1α, and VEGF expression were significantly correlated with Lauren's classification, lymph node metastasis, and pathologic staging (p < 0.05). There were positive correlations between MVD and the expression of Rac1, HIF-1α, and VEGF. The mean survival time and 5-year survival rate in cases with positive Rac1, HIF-1α, and VEGF expression and MVD ≥ 26.3 were significantly shorter than those with negative Rac1, HIF-1α, and VEGF expression and MVD < 26.3.

Conclusion: Rac1, HIF-1α, and VEGF play an important role in tumor invasion and metastasis, especially in tumor angiogenesis. Thus, testing the expression of Rac1, HIF-1α, and VEGF may be a useful index for treatment and prognosis.

Background: Unresectable locally advanced pancreatic cancer (LAPC) has an extremely poor prognosis. Results of neoadjuvant (radio-)chemotherapy approaches aiming at achieving resectability are currently not satisfactory.

Case report: We report the case of a 67-year-old woman with histologically confirmed pancreas carcinoma that was not resectable on first surgical exploration who achieved a well-documented complete pathological remission (pCR). The carcinoma became resectable after consecutive neoadjuvant treatment with nanoparticle albumin-bound (nab)-paclitaxel/gemcitabine and FOLFIRINOX chemotherapy regimens.

Conclusion: This is the first reported LAPC case in which neoadjuvant chemotherapy alone has been shown to lead to demonstrated pCR. CA19-9 levels, but not imaging criteria, were useful for response prediction and timing of the Whipple's procedure. The findings in this case suggest possible conceptual changes in the treatment approach for LAPC, and indicate that the new effective chemotherapy regimens should be integrated into clinical trials for LAPC.

Background: Cytotoxic extravasation is a rare but potentially serious and painful complication of intravenous drug administration in oncology. Literature is anecdotal, and systematic clinical trials are scarce. The German working group for Supportive Care in Cancer (ASORS) has prepared an expert opinion for the diagnosis, prophylaxis and management of cytotoxic extravasation based on an interdisciplinary expert panel.

Material and methods: A Pubmed search was conducted for diagnosis, risk factors, symptoms, prophylaxis, and treatment of extravasation by the respective responsible expert. A writing committee compiled the manuscript and proposed the level of recommendation. In a consensus meeting, 13 experts reviewed and discussed the current practice in diagnosis and management of cytotoxic extravasation. In a telephone voting among the experts, the level of recommendation by ASORS was determined.

Results: Every effort should be made to reduce the risk of extravasation. Staff training, patient education, usage of right materials and infusion techniques have been identified to be mandatory to minimalize the risk of extravasation. Extravasation must be diagnosed as soon as possible, and specific therapy including antidotes dependent on the extravasated drug should be initiated immediately. An extravasation emergency set should be available wherever intravenous cytotoxics are applied. Documentation and post-treatment follow-up are recommended.

Conclusion: We have developed a literature- and expert-based consensus recommendation to avoid cytotoxic extravasation. It also provides practical management instructions which should help to avoid surgery and serious late effects.

Background: The aim was to re-evaluate the current prevalence and management of cancer-associated anaemia as defined by the World Health Organisation (WHO) and related risk factors.

Patients and methods: This was a prospective, 2-day web-based cross-sectional survey in cancer patients with non-myeloid malignancies in German outpatient clinics.

Results: 89 centres collected data from 3,867 patients, of whom 74% received active cancer therapy. The median age was 65 years (range 19-99 years) and almost two-thirds were women; 68% of the patients had solid tumours (breast 34%, colorectal 17%, lung 8%), with 56% of them being metastatic; 73% had a WHO performance score of ≤ 1. The mean haemoglobin level was 12.0 ± 1.7 g/dl (± standard deviation; range 4.3-17.8 g/dl); the prevalence of levels below 12.0 g/dl was 49%. Two-thirds of these patients were not treated for anaemia; one-third received erythropoiesis-stimulating agents (12.6%), iron therapy (8.1%), transfusions (7.5%) or combinations thereof (8.0%) during the 4 weeks before evaluation. Chemotherapy, female sex, age and poor performance status were identified as significant anaemia-associated factors.

Conclusions: The prevalence of untreated anaemia and the decreased performance status of cancer patients in Germany have hardly changed since the European Cancer Anaemia Survey (ECAS) in 2001. The treatment practice may not only be driven by guidelines and does not yet reflect new concepts of anaemia management.