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Pugliano, Lina; Zardavas, Dimitrios; Piccart, Martine
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0104-x
The National Cancer Institute of the United States defines personalized medicine (PM) as “a form of medicine that uses information about a person’s genes, proteins and environment to prevent, diagnose and treat disease” (National Cancer Institute, Dictionary of Cancer Terms) [1]. Consequently, the ultimate dream is the generation of a “molecular fingerprint” via a simple blood test or tumor sample that allows the physician to refine an individual patient’s prognosis, select the best possible therapeutic option, and minimize the toxicity from therapies by identification of distinct genetic markers. The enormous gains to patients and ultimately health care systems are unmistakable.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0100-1
At the recent ASH meeting, updated 4 year results on the use of the second-generation tyrosine kinase inhibitor nilotinib compared with imatinib were presented and they demonstrated superiority in achieving faster and deeper molecular responses for nilotinib compared to imatinib. A rapid decrease in BCR-ABL transcripts of ≤ 10 % BCR-ABL IS at 3 months is associated with a statistically significantly superior overall survival regardless which tyrosine kinase inhibitor was used (nilotinib, dasatinib, and imatinib). By using a second-generation tyrosine kinase inhibitor, however, the chance to achieve ≤ 10 % BCR-ABL IS at 3 months is significantly higher. Some data also indicate that some caution should be taken for new and so far unknown potential side effects of second-generation tyrosine kinase inhibitors.
Nösslinger, Thomas; Nösslinger, Thomas
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0086-8
Recent clinical data presented at the annual meeting of the American Society of Hematology underline the importance of incorporating cytarabine in the induction treatment of younger patients with mantle cell lymphoma, while other trials confirmed the importance of immuno-chemotherapy with rituximab and bendamustine, especially in elderly patients. R-CHOP remains the standard for first line treatment in diffuse large B-cell lymphoma, though, several new therapeutic agents such as lenalidomide and ibrutinib are now tested in clinical trials as single agent or in combination with established therapies. Finally, some new therapeutic options for the unfavorable subset of T-cell lymphoma were presented.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0102-z
Hematopoietic stem cell transplantation (HSCT) is a developing treatment modality, continuously being adapted to disease-specific requirements, and, even more successfully, to the tolerability in a growing target population. Allogeneic HSCT, in particular, is now accessible as a curative treatment for patients that would have been allocated to palliative concepts 1 or 2 decades ago. However, modern pharmacotherapy of neoplastic diseases is advancing, taking advantage of the increasing insight into cancer biology. Therefore, the role of HSCT in the treatment of hematologic malignancies has to be defined and reconsidered in a continuous fashion. At the ASH Meeting 2012, nearly 900 abstracts covered the field of allogeneic HSCT. The short list of abstracts reviewed here was selected according to the authors’ perception of a particular clinical impact. It is aimed to cover the most relevant issues an HSCT-physician is faced with in clinical practice in 2013, namely the management of the elderly patient (typically with acute myeloid leukemia or myelodysplastic syndromes), the limitations regarding access to a suitable donor, and the management of relapse and the most important cause of nonrelapse mortality, graft versus host disease, after allogeneic HSCT.
Weiss, Lukas; Melchardt, Thomas; Greil, Richard; Hopfinger, Georg
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0099-3
Treatment of CLL has been significantly improved through combination of chemotherapy and rituximab. Furthermore, the positive influence of MRD negativity on survival was clearly demonstrated. More recently, drugs with novel modes of action, e.g. targeting B-cell receptor or downstream, chemotherapy-free therapy concepts seem to possible in the near future. More importantly, administration of new drugs with the aim to overcome unfavorable prognostic factors as 17p- or BIRC3, NOTCH1 and SF3B1 is warranted.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0106-8
This short and personal overview summarizes new data in the field of myeloproliferative neoplasms from the 2012 American Society of Hematology meeting. In Polycythemia vera (PV) an hematocrit strictly kept below 45 % was shown to be associated with a lower cardiovascular event rate. Pegylated interferon-alpha-2b showed high rates of stable hematological responses in PV. Two small studies investigated Imetelstat and Vorinostat in essential Thrombocythemia. Imetelstat is a telomerase inhibitor and demonstrated high hematological response rates with an acceptable tolerability. Vorinostat, an histone-deacetylase inhibitor, showed moderate response rates but a poor safety profile in the two investigated entities, i.e., essential thrombocythemia (ET) and PV patients. CYT387, a Janus-kinase-2 inhibitor which is not yet approved for Myelofibrosis treatment, demonstrated reductions in spleen size comparable to those known from Ruxolitinib-treated patients. Moreover, high rates of transfusion independence were observed and lasted at least 1 year in 50 % of patients. The most frequent adverse event was thrombocytopenia constituting 22 and 24 % of grade 1/2 and 3/4 events, respectively. Another JAK-inhibitor, SAR302503, investigated in a phase II trial had shown similar reductions in spleen size and a considerable decrease in symptom burden. The most frequent grade 3/4 adverse events in patients treated with SAR302503 were anemia and thrombocytopenia. The updated data from the COMFORT-I and COMFORT-II trials showed that the survival benefit, the spleen size reductions and the increase in quality of life in Ruxolitinib treated Myelofibrosis patients were maintained during the further observation to weeks 84 and 96.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0101-0
At the 2012 ASH meeting the topic “AML” was presented in the Ham–Wassermann lecture, an excellent educational symposium with numerous oral and poster presentations. Recent progress in the field of cytotoxic chemotherapy seems rather slow, but significant improvement in the understanding of the pathogenesis of acute myeloid leukemia (AML) has led to the identification of recurrent gene mutations; some of them already have changed treatment strategies in specific patients.
Willenbacher, Wolfgang; Willenbacher, Ella
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0085-9
Clonal evolutionary models of myeloma progression were the main focus with respect to basic science highlights at ASH 2012. The well-documented evidence for the existence of a “Darwinian-branching” evolution pattern has major clinical implications for the development of new treatment strategies and disease monitoring. As treatment results for myeloma have been further improved in most patient cohorts, an easy to use score for identification of high-risk patients with shortened overall survival (OS) has been established (elevated LDH, International Staging System (ISS) stage 3 disease, presence of cytogenetic aberrations t(4;14) and/or del 17p), while further evidence supporting the use of cereblon expression as a biomarker of IMiD (Thalidomid, Lenalidomide, Pomalidomide (POM)) response was presented. Multiple presentations delivered further positive evidence of the usefulness of maintenance and/or consolidation elements in myeloma therapies. A good example came from the Italian VMPT-VT vs. VMP trial proofing both a considerable progression free (11 months)—and OS benefit in a large phase III setting, comparing a quadruplet induction with doublet maintenance with a standard triplet induction therapy. In relapsed and refractory myeloma with both Bortezomib and IMiD pretreatment, POM and low dose Dexamethason were proved to be superior to high dose Dexamethason in a phase III trial that is expected to lead to drug registration of POM in the near future. Five presentations gave evidence for the applicability of Bendamustin based combination therapies in third and later lines of therapies, with good results even in elderly patients.
Melchardt, Thomas; Weiss, Lukas; Greil, Richard; Egle, Alexander
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0095-7
Modern treatment strategies have resulted in an excellent overall survival in the majority of patients with Hodgkin’s lymphoma. PET-stratification is used to guide treatment in patients with limited disease in clinical trials, but recent results indicate that combined treatment with chemotherapy and radiotherapy is still the standard of care. Prediction of treatment related mortality and new data about chemotherapy induced infertility will guide our decisions especially in patients with advanced disease and brentuximab vedotin is now an approved option in patients with relapsed or refractory disease.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0098-4
The association between cancer and the development of venous thromboembolism is well documented. Cancer-related venous thromboembolism is associated with worsened short-term as well as long-term survival—it also affects the quality of life of the patient and may delay ongoing treatment. Interaction of cancer cells as well as effects of chemotherapy can lead to a systematic activation of coagulation system. Consequently, venous thromboembolism in cancer patients has been associated with several tumor-, treatment- and patient- related risk factors. Several studies focused on possibilities to predict the risk of venous thromboembolism in cancer patients. However, patient selection for prophylactic antithrombotic treatment remains a matter of controversy. In contrast, treatment of cancer-associated venous thromboembolism using low molecular weight heparin is well established. The role of the novel anticoagulants—new oral factor Xa and thrombin inhibitors in the treatment of cancer patients with venous thromboembolism remains to be determined. In this review, recently published studies and guidelines regarding risk assessment, prevention, and treatment of cancer-associated venous thromboembolism are summarized.
Sitte, Harald H.; Freissmuth, Michael
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0094-8
Generic drugs contain the identical chemical copy of their cognate originator drug’s active ingredient and this can be proven by their physicochemical properties and the structural identity. A more complex situation is given when it comes to biological drugs, where identical copies cannot be produced. Hence, similar to the approval of the originator biological drug, great care must be employed when approving biosimilar protein drugs. Furthermore, this needs to be continued after the entrance of biological/biosmilar drugs into the market: rigorous pharmacovigilance during their application is the key and the close surveillance of their production is mandatory. In this review, we will highlight the differences between generic and biosimilar drugs and point out what healthcare professionals need to know.
Ruhstaller, Thomas; Stahl, Michael
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0096-6
There are still a lot of controversies regarding treatment strategies in oesophageal carcinoma due to lack of studies with adequate patient numbers and the inclusion of heterogeneous study populations. Some important news came from the CROSS trial regarding the value of neoadjuvant chemoradiation (CRT). Patients with resectable tumours were randomised to receive surgery alone or weekly administration of carboplatin and paclitaxel for 5 weeks and concurrent radiotherapy. The overall survival in this well-powered study was significantly improved with neoadjuvant CRT resulting in a hazard ratio of 0.657. The control arm with surgery alone showed an exceptional good prognosis with a very low postoperative mortality rate of 4 % only. Also the neoadjuvant therapy showed very good tolerability, the postoperative mortality rate was not increased after neoadjuvant CRT. Only two randomised trials investigated the value of neoadjuvant CRT vs. chemotherapy (CT) in adenocarcinomas of the oesophago-gastric junction (EGJ). Both showed a non-significant trend in favour of neoadjuvant CRT, but both trials included only a limited number of patients. The value of an induction chemotherapy before CRT is still unproven, even if there are several arguments for it and it is daily practice in a lot of centres. Another remaining controversy exists about those patients having achieved a complete response to CRT. Does surgery play a role for the curative therapy of these patients or not? Also this issue is discussed in this review.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0097-5
Image-guided percutaneous radiofrequency ablation (RFA) is a viable treatment option for unresectable liver metastasis from gastrointestinal cancer. With optimized technology and sufficient safety margins, RFA reaches oncologic results comparable to surgery. However, use of RFA for resectable liver metastases is controversially discussed. The feasibility and success of RFA depend on the size and location of the liver lesion. Single-needle in-plane techniques have important limitations and may be largely overcome by multineedle approaches using 3D treatment planning and stereotactic needle guidance. The major obstacle for the acceptance of RFA is the current lack of an international standardized definition and documentation of treatment success. In analogy to surgical R0 resection, A0 ablation including a 3D safety margin of at least 5 mm, objectively verified and documented by true fusion of post- with preablation images has to be demanded. Considering the patient’s huge advantage of a minimal invasive local therapy, options for RFA should be discussed in interdisciplinary oncologic boards and communicated to the patient. Randomized controlled studies for getting answers to whether A0 ablation may prove as a true alternative to surgical resection in liver metastasis from gastrointestinal cancer are heavily awaited.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0108-6
Until the late 1990’s colorectal cancer had a poor prognosis with a median survival of 12 months for metastatic disease. The discovery of molecular mechanisms for malignant transformation, tumor growth, angiogenesis, and metastasis formation have opened an abundance of biologic insights and subsequent therapeutic approaches, which have led to improved prognosis in many cancers, among them colorectal cancer. While inhibition of vascular endothelial growth factor (VEGF) either by blocking antibodies or synthetic soluble receptor fragments—the so-called VEGF-traps—have been shown to be beneficial when combined with chemotherapy, blocking antibodies against the epidermal growth factor receptor (EGFR) have revealed cytotoxic activity as monotherapy or in combination with chemical agents. Recently, the tyrosine kinase inhibitor regorafenib has been shown to be beneficial as a monotherapy in the salvage treatment setting for metastatic colorectal cancer (mCRC) patients. However, as major driver mechanisms for malignant transformation in colorectal cancer have so far not been accounted, we may expect an abundance of novel therapeutic options in CRC. In this review, novel promising therapeutic approaches will be outlined.
2013 memo - Magazine of European Medical Oncology
doi: 10.1007/s12254-013-0105-9
Overall survival of patients suffering from upper gastrointestinal (GI) cancer is still poor. Most of the patients are diagnosed in advanced stages. But even in patients with operable disease, the recurrence rates, especially of gastric and pancreatic neoplasias, are still very high. Much effort has therefore been put in the development of palliative and curative therapeutic concepts. The aim of this article is to summarize the most important publications presented at American Society of Clinical Oncology (ASCO) 2013 concerning gastric and pancreatic cancer with the main focus on relevance for clinical practice.