Phase I study of gemcitabine using a once every 2 weeks schedule.

Gemcitabine (2',2'-difluorodeoxycytidine) is a novel nucleoside analogue. As part of a series of studies to determine the maximum tolerated dose (MTD) of gemcitabine and the most appropriate schedule, a two-centre phase I study of gemcitabine was undertaken in patients with advanced refractory solid tumours using a once every 2 weeks schedule. Fifty-two patients were entered into the study at 14 different dose levels (40-5700 mg m-2). Weekly evaluations for toxicity were performed and the MTD for this once every 2 weeks schedule was 5700 mg m-2. The dose-limiting toxicity was myelosuppression, with neutropenia being most significant. Other toxicities were nausea, vomiting, fever and asthenia. One minor response was seen in a heavily pretreated breast cancer patient treated at 1200 mg m-2. Preclinical studies suggest that the efficacy of gemcitabine is more schedule than dose related, and it is concluded that this is not the most appropriate dosing schedule for gemcitabine. However, this study demonstrates the safety profile of gemcitabine, as doses over fourfold greater than that recommended for the weekly schedule of 1000 mg m-2 could be tolerated

Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies—(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician—scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framewor

Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck

Background: Radiation dermatitis occurs to some degree in most patients receiving radiotherapy, with or without chemotherapy. Patients with squamous cell carcinoma of the head and neck (SCCHN) who receive radiotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, may develop a characteristic acne-like rash in addition to dermatitis. Design: An advisory board of 11 experienced radiation oncologists, medical oncologists and dermatologists discussed the management options for skin reactions in patients receiving EGFR inhibitors and radiotherapy for SCCHN. Skin toxicity was categorised according to the National Cancer Institute—Common Terminology Criteria for Adverse Events (version 3) grading. Results: Both general and grade-specific approaches for the management of dermatitis in this patient group are presented. It was concluded that where EGFR inhibitor-related acne-like rash and dermatitis coexist within irradiated fields, management should be based on the grade of dermatitis: for grade 1 (or no dermatitis), treatment recommendations for EGFR-related acne-like rash outside irradiated fields should be followed; for grades 2 and above, treatment recommendations for dermatitis were proposed. Conclusions: This paper presents comprehensive consensus guidelines for the treatment of dermatitis in patients with SCCHN receiving EGFR inhibitors in combination with radiotherap