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Warsaw, Poland

A woman with mucoepidermal tumor of right maxilla was operated upon (radical maxillectomy) 35 years ago. After a follow-up period of 16 years a recurrent tumor was removed and she underwent postoperative radiotherapy. After further15 years a recurrent tumor involving the face and the right intracranial fossa appeared together with pulmonary metastases. The patient is now in a good general condition. Because of the advancement and slow course of the disease she was not referred for further treatment. Source

Ismael G.,Hospital Amaral Carvalho | Hegg R.,University of Sao Paulo | Muehlbauer S.,Hoffmann-La Roche | Heinzmann D.,Hoffmann-La Roche | And 7 more authors.
The Lancet Oncology | Year: 2012

Background: A subcutaneous formulation of trastuzumab has been developed, offering potential improvements in patient convenience and resource use compared with the standard intravenous infusion of the drug. We compared the pharmacokinetic profile, efficacy, and safety of the subcutaneous and intravenous formulations in patients with HER2-positive early breast cancer. Methods: The HannaH study was a phase 3, randomised, international, open-label, trial in the (neo)adjuvant setting. Patients with HER2-positive, operable, locally advanced or inflammatory breast cancer were randomly assigned to eight cycles of neoadjuvant chemotherapy administered concurrently with trastuzumab every 3 weeks either intravenously (8 mg/kg loading dose, 6 mg/kg maintenance dose) or subcutaneously (fixed dose of 600 mg); 1:1 ratio. Chemotherapy consisted of four cycles of docetaxel (75 mg/m 2) followed by four cycles of fluorouracil (500 mg/m 2), epirubicin (75 mg/m 2), and cyclophosphamide (500 mg/m 2), every 3 weeks. After surgery, patients continued trastuzumab to complete 1 year of treatment. Coprimary endpoints were serum trough concentration (C trough) at pre-dose cycle 8 before surgery (non-inferiority margin for the ratio between groups of 0·80) and pathological complete response (pCR; non-inferiority margin for the difference between groups of -12·5%), analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT00950300. Findings: 299 patients were randomly assigned to receive intravenous trastuzumab and 297 to receive subcutaneous trastuzumab. The geometric mean presurgery C trough was 51·8 μg/mL (coefficient of variation 52·5%) in the intravenous group and 69·0 μg/mL (55·8%) in the subcutaneous group. The geometric mean ratio of C trough subcutaneous to C trough intravenous was 1·33 (90% CI 1·24-1·44). 107 (40·7%) of 263 patients in the intravenous group and 118 (45·4%) of 260 in the subcutaneous group achieved a pCR. The difference between groups in pCR was 4·7% (95% CI -4·0 to 13·4). Thus subcutaneous trastuzumab was non-inferior to intravenous trastuzumab for both coprimary endpoints. The incidence of grade 3-5 adverse events was similar between groups. The most common of these adverse events were neutropenia (99 [33·2%] of 298 patients in the intravenous group vs 86 [29·0%] of 297 in the subcutaneous group), leucopenia (17 [5·7%] vs 12 [4·0%]), and febrile neutropenia (10 [3·4%] vs 17 [5·7%]). However, more patients had serious adverse events in the subcutaneous group (62 [21%] of 297 patients) than in the intravenous group (37 [12%] of 298); the difference was mainly attributable to infections and infestations (24 [8·1%] in the subcutaneous group vs 13 [4·4%] in the intravenous group). Four adverse events led to death (one in the intravenous group and three in the subcutaneous group), all of which occurred during the neoadjuvant phase. Of these, two-both in the subcutaneous group-were deemed to be treatment related. Interpretation: Subcutaneous trastuzumab, administered over about 5 min, has a pharmacokinetic profile and efficacy non-inferior to standard intravenous administration, with a similar safety profile to intravenous trastuzumab, and therefore offers a valid treatment alternative. © 2012 Elsevier Ltd. Source

Kaye S.B.,Institute of Cancer Research | Poole C.J.,University of Warwick | Danska Bidzinska A.,Centrum Onkologii | Gianni L.,Istituto Nazionale dei Tumori | And 8 more authors.
Annals of Oncology | Year: 2013

Background: Pertuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor (HER)-mediated signalling, has shown activity in ovarian cancer in preclinical models and in the clinic. This randomized phase II study evaluated efficacy and safety of pertuzumab in combination with carboplatin-based chemotherapy in patients with platinum-sensitive, recurrent advanced ovarian cancer. Patients and methods: Patients were randomized to receive six cycles of chemotherapy (carboplatin and either paclitaxel (Taxol) or gemcitabine) with or without pertuzumab. The primary end point was progression-free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumors and/or by CA 125 measurements. Secondary end points evaluated the response rate, safety profile, duration of response, time to progression and overall survival for both treatment arms. Results: A total of 149 patients received either chemotherapy with pertuzumab (arm A, n = 74) or chemotherapy alone (arm B, n = 75). There was no significant difference either in median PFS or in the secondary end points between the two arms. No differences were seen in an exploratory biomarker analysis of HER3 mRNA expression between the two arms. Pertuzumab was well tolerated, with no increase in cardiac adverse events compared with chemotherapy alone. Conclusions: The addition of pertuzumab to carboplatin-based chemotherapy did not substantially prolong PFS in unselected patients with platinum-sensitive ovarian cancer. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

This paper presents some details concerning the first few years after discovery of X-rays by Roentgen. Progress in radiotherapy during 120 years is discussed and illustrated by diagrams of milestones in the physics, technology and methods of radiation therapy. Discussion is focused on two topics: "physics versus biology" and "empirical radiotherapy versus clinical trials". Evolution of radiotherapy has been based on the so-called "Paterson school" for the first 50 years which moved since 1968 into the "Fletcher school". Rationale of this school was based on experimental and clinical radiobiology studies carried out in the 1950s-1970s, recognised almost all mechanisms of tumour and normal tissue response to radiation. For over 80 years, retrospective clinical studies and empirical experience have built up the fundamentals of modern radiotherapy and have served to design clinical trials. However, many "evidence based trials" provide some uncertainties and offer only average results as guidelines to treat individual patients. Trials are critically discussed based on the results of the selected studies with suggestions for careful interpretation based on logic and practical common sense. Studies of molecular biology and genetics clearly show that each tumour has own individual "fingerprint", which moves all oncology including radiotherapy to individual personalised therapy. This is an important challenge for near future. © Polskie Towarzystwo Onkologiczne. Source

Motzer R.J.,Sloan Kettering Cancer Center | Hutson T.E.,Texas Oncology | Glen H.,Beatson West of Scotland Cancer Center | Michaelson M.D.,Massachusetts General Hospital | And 12 more authors.
The Lancet Oncology | Year: 2015

Background: Currently, metastatic renal cell carcinoma is treated with sequential single agents targeting VEGF or mTOR. Here, we aimed to assess lenvatinib, everolimus, or their combination as second-line treatment in patients with metastatic renal cell carcinoma. Methods: We did a randomised, phase 2, open-label, multicentre trial at 37 centres in five countries and enrolled patients with advanced or metastatic, clear-cell, renal cell carcinoma. We included patients who had received treatment with a VEGF-targeted therapy and progressed on or within 9 months of stopping that agent. Patients were randomised via an interactive voice response system in a 1:1:1 ratio to either lenvatinib (24 mg/day), everolimus (10 mg/day), or lenvatinib plus everolimus (18 mg/day and 5 mg/day, respectively) administered orally in continuous 28-day cycles until disease progression or unacceptable toxic effects. The randomisation procedure dynamically minimised imbalances between treatment groups for the stratification factors haemoglobin and corrected serum calcium. The primary objective was progression-free survival in the intention-to-treat population. This study is closed to enrolment but patients' treatment and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT01136733. Findings: Between March 16, 2012, and June 19, 2013, 153 patients were randomly allocated to receive either the combination of lenvatinib plus everolimus (n=51), single-agent lenvatinib (n=52), or single-agent everolimus (n=50). Lenvatinib plus everolimus significantly prolonged progression-free survival compared with everolimus alone (median 14·6 months [95% CI 5·9-20·1] vs 5·5 months [3·5-7·1]; hazard ratio [HR] 0·40, 95% CI 0·24-0·68; p=0·0005), but not compared with lenvatinib alone (7·4 months [95% CI 5·6-10·2]; HR 0·66, 95% CI 0·30-1·10; p=0·12). Single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone (HR 0·61, 95% CI 0·38-0·98; p=0·048). Grade 3 and 4 events occurred in fewer patients allocated single-agent everolimus (25 [50%]) compared with those assigned lenvatinib alone (41 [79%]) or lenvatinib plus everolimus (36 [71%]). The most common grade 3 or 4 treatment-emergent adverse event in patients allocated lenvatinib plus everolimus was diarrhoea (ten [20%]), in those assigned single-agent lenvatinib it was proteinuria (ten [19%]), and in those assigned single-agent everolimus it was anaemia (six [12%]). Two deaths were deemed related to study drug, one cerebral haemorrhage in the lenvatinib plus everolimus group and one myocardial infarction with single-agent lenvatinib. Interpretation: Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. Further study of lenvatinib is warranted in patients with metastatic renal cell carcinoma. Funding: Eisai Inc. © 2015 Elsevier Ltd. Source

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