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Hong, T S; Ritter, M A; Tomé, W A; Harari, P M
doi: 10.1038/sj.bjc.6602577pmid: 15856036
The use of intensity-modulated radiation therapy (IMRT) is rapidly advancing in the field of radiation oncology. Intensity-modulated radiation therapy allows for improved dose conformality, thereby affording the potential to decrease the spectrum of normal tissue toxicities associated with IMRT. Preliminary results with IMRT are quite promising; however, the clinical data is relatively immature and overall patient numbers remain small. High-quality IMRT requires intensive physics support and detailed knowledge of three-dimensional anatomy and patterns of tumour spread. This review focuses on basic principles, and highlights the clinical implementation of IMRT in head and neck and prostate cancer.
doi: 10.1038/sj.bjc.6602582pmid: 15870717
Radiofrequency ablation (RFA) provides an effective technique for minimally invasive tissue destruction. An alternating current delivered via a needle electrode causes localised ionic agitation and frictional heating of the tissue around the needle. Image-guided, percutaneous ablation techniques have been developed in most parts of the body, but the most widely accepted applications are for the treatment of hepatocellular carcinoma (HCC) in early cirrhosis, limited but inoperable colorectal liver metastases, inoperable renal cell carcinoma and inoperable primary or secondary lung tumours. The procedures are well tolerated and the complication rates low. Patients with coexistent morbidity who are not suitable for surgery are often able to undergo RFA. Most treatments in the lung, kidney and for HCC are performed under conscious sedation with an overnight hospital stay or as a day-case. Larger more complicated ablations, for example, in hepatic metastases may require general anaesthesia. Limitations of RFA include the volume of tissue that can be ablated in a timely fashion, that is, most centres will treat 3–5 tumours up to 4–5 cms in diameter. Early series reporting technical success and complications are available for lung and renal ablation. Liver ablation is better established and 5-year survival figures are available from several centres. In patients with limited but inoperable colorectal metastases, the 5-year survival ranges from 26 to 30% and for HCC it is just under 50%. In summary, RFA provides the opportunity for localised tissue destruction of limited volumes of tumour; it can be offered to nonsurgical candidates and used in conjunction with systemic therapy.
doi: 10.1038/sj.bjc.6602565pmid: 15841075
A joint workshop held by Cancer Research UK and the Medical Research Council aimed to stimulate interest in further research into the area of cancer cachexia. The workshop was divided into four sessions: an overview of cancer cachexia, potential mechanisms involved and methodologies that might be used to understand cachexia, and also the experience of cachexia from other disease areas. The workshop identified a need to develop a multimodal therapeutic approach to cancer cachexia and a need to undertake more multidisciplinary research.
Forrest, L M; McMillan, D C; McArdle, C S; Angerson, W J; Dagg, K; Scott, H R
doi: 10.1038/sj.bjc.6602591pmid: 15870712
The value of an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was compared with performance status (ECOG-ps) in a longitudinal study of patients (n=101) with inoperable non-small-cell lung cancer (NSCLC). At diagnosis, stratified for treatment, only the GPS (HR 2.32, 95% CI 1.52–3.54, P<0.001) was a significant predictor of survival. In contrast, neither the GPS nor ECOG-ps measured at 3–6 months follow-up were significant predictors of residual survival. This study confirms the prognostic value of the GPS, at diagnosis, in patients with inoperable NSCLC. However, the role of the GPS and ECOG-ps during follow-up has not been established.
Camidge, D R; Randall, K R; Foster, J R; Sadler, C J; Wright, J A; Soames, A R; Laud, P J; Smith, P D; Hughes, A M
doi: 10.1038/sj.bjc.6602558pmid: 15886708
We have demonstrated the feasibility of detecting and quantifying six cell-cycle-related nuclear markers (Ki67, pRb, p27, phospho-p27 (phosphorylated p27), phospho-pRb (phosphorylated pRb), phospho-HH3 (phosphorylated histone H3)) in plucked human scalp and eyebrow hair. Estimates of the proportion of plucked hairs that are lost or damaged during processing plus the intra- and intersubject variability of each nuclear marker with these techniques are provided to inform sizing decisions for intervention studies with drugs potentially impacting on these markers in the future.
Dejardin, O; Bouvier, A-M; Herbert, C; Velten, M; Buemi, A; Delafosse, P; Maarouf, N; Boutreux, S; Launoy, G
doi: 10.1038/sj.bjc.6602571pmid: 15886707
The aim of this study was to investigate the relationship between social and geographic characteristics and the type of care centre for initial colorectal surgery in France. Patients living far from a reference cancer site were less frequently treated in a reference cancer site than those who were living near a reference cancer site ORa=(0.50 (0.33–0.76)). As for topography and emergency presentation, place of residence (urban/rural), occupation and marital status were not associated with the type of the care centre. Improvements in diagnosis and treatment and of clinical practice guidelines are therefore crucial to ensure equality in health care in France.
Veronese, M L; Sun, W; Giantonio, B; Berlin, J; Shults, J; Davis, L; Haller, D G; O'Dwyer, P J
doi: 10.1038/sj.bjc.6602569pmid: 15870719
Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy of colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive growth inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study to determine the tolerability and efficacy of gefitinib in combination with irinotecan, infusional 5-fluorouracil (5-FU) and leucovorin (LV), on a 2-week schedule. Among 13 patients with advanced colorectal cancer, 10 required dose reductions of irinotecan and 5-FU because of dehydration, diarrhoea, and neutropenia, seven of whom required hospitalisation, three with neutropenic fever. One patient achieved partial response and seven had disease stabilisation. The combination of this standard chemotherapy regimen with gefitinib is associated with excessive toxicity, suggesting an interaction at a pharmacokinetic or pharmacodynamic level.
Kim, S T; Kang, W K; Kang, J H; Park, K W; Lee, J; Lee, S-H; Park, J O; Kim, K; Kim, W S; Jung, C W; Park, Y S; Im, Y-H; Park, K
doi: 10.1038/sj.bjc.6602575pmid: 15870718
We performed a phase II study of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU) and leucovorin in metastatic gastric cancer patients who were previously treated with taxane and cisplatin, to evaluate the antitumour activity and toxicity of the combination chemotherapy. The metastatic gastric adenocarcinoma patients who were previously treated with taxane and cisplatin combination as first line, and had at least one measurable lesion, 0–2 ECOG performance status and adequate organ functions, were considered eligible. They received irinotecan (150 mg m−2, day 1) and leucovorin (100 mg m−2, day 1), followed by continuous infusion of 5-FU (1000 mg m−2 day−1, days 1 and 2) every 2 weeks. Treatment was continued until progression of disease was observed. In all, 64 patients were treated with this combination chemotherapy. The median age of the patients was 55 years (range, 33–74 years), and the median ECOG performance status was 1 (0–1, 61 (95%)). Out of 64 patients, 57 were assessable for response. Among 57 assessable patients, no complete response and 12 partial responses were observed (overall response rate, 21%; 95% confidence interval (CI), 10–32%). Stable disease was observed in 14 patients (25%) and progressive disease in 31 patients (54%). The median time to progression was 2.5 months (95% CI, 1.6–3.4) and the median overall survival since the start of the second-line modified FOLFIRI was 7.6 months (95% CI, 6.5–8.7). Grade 3–4 haematologic toxicities included neutropenia in seven patients (11%) and thrombocytopenia in five patients (8%). Grade 3–4 nonhaematologic toxicities included diarrhoea in two patients (3%) and vomiting in two patients (3%). There were no treatment-related deaths. The combination of irinotecan, 5-FU and leucovorin showed moderate activity and favourable toxicity profile as a second-line treatment in metastatic gastric cancer patients, who were previously treated with taxane and cisplatin.
Awada, A; Hendlisz, A; Gil, T; Bartholomeus, S; Mano, M; de Valeriola, D; Strumberg, D; Brendel, E; Haase, C G; Schwartz, B; Piccart, M
doi: 10.1038/sj.bjc.6602584pmid: 15870716
BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor (VEGFR) inhibitor that targets tumour cell proliferation and tumour angiogenesis. This Phase I study was undertaken to determine the safety profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and tumour response profile of oral BAY 43-9006 in patients with advanced, refractory solid tumours. BAY 43-9006 was administered daily for repeated cycles of 21 days on/7 days off. A total of 44 patients were enrolled at doses from 50 to 800 mg b.i.d. Pharmacokinetic profiles of BAY 43-9006 in plasma were determined during the first treatment cycle. The most frequently reported adverse events over multiple cycles were gastrointestinal (75%), dermatologic (71%), constitutional (68%), pain (64%), or hepatic (61%) related. A MTD of 400 mg b.i.d. BAY 43-9006 was defined. BAY 43-9006 was absorbed rapidly; steady-state conditions were reached within 7 days. BAY 43-9006 exposure increased nonproportionally with increasing dose. In all, 32 patients were evaluated for tumour response: 15 patients showed tumour progression, 16 patients experienced stable disease (>6 months in eight patients), and one patient with renal cell carcinoma achieved a partial response. BAY 43-9006 given for 21 days with 7 days off treatment was safe, well tolerated, and showed antitumour activity.
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