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In the EU, the centralized procedure (CP) of the EMA is mandatory for marketing authorization for innovative anticancer drugs. However, numerous independent healthcare systems are in operation across the EU, and each HTA body follows its own methodologies and scientific value judgements in the assessment of the added value of an innovative anticancer drug. Initiatives to improve the interface between the different stakeholders are currently on the way, but are unlikely sufficient enough to overcome these fundamental problems.

Background Little is known about the prevalence and associations of clinically relevant fatigue (CRF) in recurrence-free prostate cancer survivors. Patients and methods Four hundred and sixteen recurrence-free prostate cancer survivors who were >1 year post-radiotherapy or radical prostatectomy were surveyed. The prevalence of CRF (defined as Brief Fatigue Inventory >3) was determined and compared with a noncancer control group. Other measures included the Hospital Anxiety and Depression Scale, International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Relationships between these factors and CRF were explored in univariate and multivariate analyses. Results Analyzable data were obtained from 91% (377/416) of patients. The prevalence of CRF was 29% (108/377) versus 16% (10/63) in the controls (P = 0.031). CRF was more common in post-radiotherapy than in post-prostatectomy 33% (79/240) versus 22% (29/133), P = 0.024. However, when other factors (current depression, anxiety, urinary symptoms, medical comorbidities, pain and insomnia) were controlled for, previous treatment did not predict CRF. Current depression [Hospital Anxiety and Depression Scale ≥8 was by far the strongest association [odds ratio 9.9, 95% confidence interval 4.2–23.5)]. Conclusions Almost one-third of recurrence-free prostate cancer survivors report CRF. Depression, anxiety, urinary symptoms, pain and insomnia measured at outcome are more strongly associated than type of cancer treatment previously received.

Galectin-3 plays an important role in adhesion, proliferation, differentiation, angiogenesis and metastasis in multiple tumours. To investigate the role of galectin-3 in melanoma pathogenesis we examined the expression of galectin-3 in melanocytic lesions and analysed the correlation between galectin-3 expression and clinicopathologic factors including patient survival and BRAF mutation status.We evaluated the expression of galectin-3 in 53 cases of benign naevi, 31 cases of dysplastic naevi, 59 in-situ melanomas, 314 cases of primary melanoma and 69 metastatic melanomas using tissue microarray and immunohistochemistry.Marked differences in expression of galectin-3 were seen between different categories of melanocytic lesions (ANOVA p0.0001). An increase in expression of galectin-3 between benign naevi and thin primary melanomas and a progressive decrease in expression between thin primary melanomas and thicker melanomas or metastatic melanomas was seen. Strong galectin-3 expression was associated with improved overall survival (p=0.002 and p=0.0002 for cytoplasmic and nuclear expression, respectively) and melanoma-specific survival (p=0.017 and p=0.003 for cytoplasmic and nuclear expression, respectively). A multifactorial Cox regression analysis suggested that galectin-3 expression was an independent prognostic marker for overall survival in melanoma (risk ratio 0.73, 95% CI 0.547-0.970, p=0.031 for cytoplasmic expression and risk ratio 0.76, 95% CI 0.587-0.985, p=0.036 for nuclear expression). No association between galectin-3 expression and BRAF mutation status was observed.This study suggests that galectin-3 is a marker of progression in melanocytic lesions and a novel prognostic marker in primary melanoma.

BACKGROUND: Safety and cellular immunogenicity of rising doses and varying regimens of a poly-epitope vaccine were evaluated in advanced metastatic melanoma. The vaccine comprised plasmid DNA and recombinant modified vaccinia virus Ankara (MVA) both expressing a string (Mel3) of seven HLA.A2/A1 epitopes from five melanoma antigens. METHODS: Forty-one HLA-A2 positive patients with stage III/IV melanoma were enrolled. Patient groups received one or two doses of DNA.Mel3 followed by escalating doses of MVA.Mel3. Immunisations then continued eight weekly in the absence of disease progression. Epitope-specific CD8+ T cell responses were evaluated using ex-vivo tetramer and IFN-gamma ELISPOT assays. Safety and clinical responses were monitored. RESULTS: Prime-boost DNA/MVA induced Melan-A-specific CD8+ T cell responses in 22/31 (71%) patients detected by tetramer assay. ELISPOT detected a response to at least one epitope in 10/31 (32%) patients. T cell responder rates were

Background Tumour necrosis factor-α (TNF-α) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-α monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. Patients and methods Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-α, CCL2, IL-6 and C-reactive protein (CRP). Results Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-α was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10–50+ weeks). There was no evidence of disease acceleration in any patient. Conclusions Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-α and CCL2 being correlated with infliximab response.

BACKGROUND. Clinicopathological features and outcome of women with endo-metrioid and serous ovarian adenocarcinoma were compared. METHODS. Between 1984 and 2004, baseline and follow-up data were prospectively recorded on 1545 patients with ovarian cancer. Of these, 270 had pure endometrioid tumors; 659 had pure serous adenocarcinoma of the ovary. Response to platinum-based chemotherapy (PBC) overall survival, stage-for-stage median progression-free survival (PFS), and cause-specific median survival were compared. Independent predictors of survival were examined by using multivariate analyses. RESULTS. Median age of diagnosis for patients with endometrioid tumors was younger than those with serous adenocarcinoma of the ovary (60 years vs 62 years; P =.013). They presented more often with early disease (stage I and 11; 50% vs 17%; P

Contains fulltext : 49133ravic.pdf (Publisher’s version ) (Closed access) E7070 is a synthetic chloro-indolyl sulphonamide that is being developed as an anti cancer agent. In this phase II study, 28 patients with metastatic melanoma received 700 mg/m(2) of E7070 as a 60-min infusion repeated every 3 weeks. Although therapy was well tolerated, with one patient receiving 14 courses of treatment, there were only minor responses on independent radiological review. E7070 does not warrant further development as a single agent for the treatment of metastatic melanoma.

BACKGROUND A review of clinicopathologic features and outcome in women with carcinosarcoma of the ovary (also known as malignant mixed mesodermal tumor [MMMT]) compared with a group of women with serous adenocarcinoma (SAC) of the ovary was conducted. METHODS Between 1984 and 2002, 1568 patients with epithelial ovarian carcinoma and 70 patients with ovarian carcinosarcoma underwent treatment at the Edinburgh Cancer Centre. Analysis was performed on 65 patients with MMMT, and 746 patients with SAC were selected as a group for comparison. Baseline variables were recorded prospectively and response to chemotherapy and progression-free and cause-specific survival between the groups were compared. RESULTS Patients with carcinosarcoma had a mean age of 66.6 years, which is significantly older than those with SAC (62.0 years) (P < 0.001). The objective response rate to platinum-based chemotherapy was found to be significantly lower in patients with carcinosarcoma (25% vs. 60%; P = 0.02). Cause-specific survival in the carcinosarcoma group was poor and significantly shorter than that observed in the SAC group (median survival of 8.2 months vs. 20.7 months; P < 0.0001). Progression-free survival in patients with carcinosarcoma also was found to be significantly shorter compared with patients with SAC (median progression-free survival of 6.4 months vs. 12.1 months; P < 0.001). Achieving optimal debulking at the time of initial surgery was found to be a highly significant factor in patients with carcinosarcoma with regard to determining outcome (median survival of 14.8 months for patients with optimally debulked International Federation of Gynecology and Obstetrics Stage III disease vs. 3.1 months for patients with suboptimally/nondebulked Stage III disease; P < 0.001). CONCLUSIONS Ovarian carcinosarcoma is a distinct entity with a poor prognosis. Patients with carcinosarcoma differ from those with SAC with regard to having an older mean age of onset, an inferior response to platinum-based chemotherapy, and worse progression-free and cause-specific survival. The extent of benefit from chemotherapy is unclear. Cancer 2004. © 2004 American Cancer Society.

In March 2003, an international mulltidisciplinary group of scientists and clinicians with a specific interest in ovarian cancer met for 4 days to discuss research into and treatment of this challenging disease. Under the headings of molecular genetics, molecular biology, the biology of ovarian cancer, old therapies, new targets and the early detection of the disease, this Position Paper summarises the presentations and discussion from the 9th Biennial Helene Harris Memorial Trust Forum on Ovarian Cancer. In particular, we highlight the potential of international collaborations in translating laboratory science into useful clinical interventions. (C) 2003 Elsevier Ltd. All rights reserved.

Mixed mesodermal tumours (MMTs) are relatively rare gynaecological tumours that have been poorly studied in clinical and molecular terms. They are chemosensitive (at least initially), although ultimately they have a poor prognosis. The biology of the tumour is fascinating in view of its composition of both epithelial and mesenchymal entities. We review herein the literature on the clinical and biological aspects of this malignancy.

About 6000 women in the United Kingdom develop ovarian cancer each year and about two-thirds of the women will die from the disease. Establishing the prognosis of a woman with ovarian cancer is an important part of her evaluation and treatment. Prognostic models and indices in ovarian cancer should be developed using large databases and, ideally, with complete information on both prognostic indicators and long-term outcome. We developed a prognostic model using Cox regression and multiple imputation from 1189 primary cases of epithelial ovarian cancer (with median follow-up of 4.6 years). We found that the significant (P≤ 0.05) prognostic factors for overall survival were age at diagnosis, FIGO stage, grade of tumour, histology (mixed mesodermal, clear cell and endometrioid versus serous papillary), the presence or absence of ascites, albumin, alkaline phosphatase, performance status on the ZUBROD-ECOG-WHO scale, and debulking of the tumour. This model is consistent with other models in the ovarian cancer literature; it has better predictive ability and, after simplification and validation, could be used in clinical practice. http://www.bjcancer.com © 2001 Cancer Research Campaignhttp://www.bjcancer.com

PURPOSE: This phase I/II study was performed to evaluate the feasibility of administering the topoisomerase inhibitor topotecan in combination with carboplatin. PATIENTS AND METHODS: Topotecan was given as a 30-minute infusion daily for 5 days, with carboplatin given immediately after topotecan on day 5. Treatment was repeated every 21 days. Carboplatin and then topotecan were escalated in sequential cohorts of three to six patients. Four dosage combinations of topotecan days 1 to 5 and carboplatin (day 5) were tested: 0.5 mg/m2/d and carboplatin area under the curve (AUC) of 4, topotecan 0.5 mg/m2/d and carboplatin AUC of 5, topotecan 0.75 mg/m2/d and carboplatin AUC of 5, and topotecan 1.0 mg/m2/d and carboplatin AUC of 5. RESULTS: Grade 3 and 4 neutropenia was common at doses of 0.75 mg/m2/d and above, but dose-limiting hematologic toxicity occurred in only one patient. The most common reason for dose reduction or delay was failure of myelosuppression to resolve by day 21. Nonhematologic toxicity was generally mild. The maximum-tolerated dose as defined in the protocol was not reached, but topotecan dose escalation was stopped at 1.0 mg/m2/d, because delayed neutrophil recovery precluded re-treatment on a 21-day schedule. CONCLUSION: Hematologic toxicity was common but rarely serious, and the combination of topotecan with carboplatin on this schedule was safe and well tolerated. Giving carboplatin to patients after topotecan on day 5, rather than on day 1, allowed dose escalation beyond the levels reported in other studies. The recommended doses for previously treated patients are topotecan 0.75 mg/m2/d, days 1 to 5, with carboplatin at an area under the curve (AUC) of 5 following topotecan on day 5. The combination of topotecan 1 mg/m2/d, days 1 to 5, followed on day 5 by carboplatin at an AUC of 5, merits further examination in untreated patients.

In 1989, the Scottish melanoma group initiated a randomized trial, comparing observation alone with 6 months' therapy with low dose interferon α (given subcutaneously 3 MU day–1, thrice weekly), for patients with primary melanomas of at least 3 mm Breslow thickness, or with evidence of regional node involvement. The trial was closed in 1993 with only 95 eligible patients randomized. There were no toxic deaths, and no patient failed to complete the treatment for reasons of toxicity. 6 months' treatment with low-dose interferon-α resulted in a statistically significant improved disease-free survival for up to 24 months after randomization (P< 0.05). However, at a median follow-up of over 6 years, although there was an apparent improvement in disease-free survival (from 9 to 22 months), and overall survival (from 27 to 39 months), consistent with larger studies powered to detect such differences, these differences were not statistically significant. The data therefore suggest that 6 months of low-dose interferon is active, and confirm the importance of the large randomized studies, such as the UKCCCR AIM-High and EORTC trials, that seek to confirm a possible survival advantage for low or intermediate dose interferon. © 2001 Cancer Research Campaign http://www.bjcancer.com

Two multicentre phase II trials were designed to determine if tumour responses can be achieved in progressive small-cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC) patients treated with ISIS 5132, an inhibitor of C-raf kinase mRNA expression (CGP 69846A; ISIS Pharmaceuticals Inc, Carlsbad, CA), and to further characterise the safety of the compound. Between August 1998 and November 1999, 26 patients (18 NSCLC, 8 SCLC) were entered. Out of these, 23 were eligible, 22 (18 NSCLC, 4 SCLC) were treated with ISIS 5132 (2 mg/kg/day, 21 days continuous intravenous (i.v.) infusion every 4 weeks) and were evaluable for toxicity and 18 (15 NSCLC, 3 SCLC) were evaluable for efficacy. For the whole group haematological toxicity did not exceed grade 2. One patient experienced a grade 4 increased prothrombin time. Non-haematological toxicity was mild to moderate, with the observation of asthenia and nausea and vomiting. Progressive disease (PD) was diagnosed in 10 patients (8 NSCLC and 2 SCLC). 8 more patients (7 NSCLC, 1 SCLC) were considered as treatment failures. In conclusion, this study using ISIS 5132 with this dose and schedule of administration excludes a 20% response rate with 95% confidence intervals for NSCLC and cannot draw any conclusions for SCLC patients as only a few were involved in the study.

The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m2. Other toxicities > or = CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t(1/2) at 180 mg/m2 = 14.1 h) and the urinary elimination of the unchanged drug was < 10%. In a patient with previously treated small cell lung carcinoma (SCLC), a 49% reduction in measurable disease was noted with resolution of pericardial and pleural effusions (120 mg/m2 x eight cycles). From the results of this phase I study a dose of 180 mg/m2 as a 1 h infusion every 3 weeks would be recommended for phase II trials.

3,5-Dichloro-2,4-dimethoxy-6-(trichloromethyl)pyridine (penclomedine, NSC 338720, CRC 88-04) is an alpha-picoline derivative with anti-tumour activity in preclinical models. Penclomedine administration by 1-h intravenous infusion on 5 consecutive days was repeated 3 weekly in the absence of dose-limiting toxicity (DLT) or disease progression. Five dose levels were investigated (22.5-340 mg m(-2) day[-1]). Eight men and eight women were entered, median age 59 years (range 39-73 years), with good performance status (ECOG 0/1) in 11 patients. A total of 13 out of 16 patients had received previous chemotherapy. Common toxicity criteria grade (CTCg) II vomiting was recorded at all dose levels. Neurotoxicity (cerebellar ataxia and dizziness) was the DLT, CTCg III toxicity occurring in three out of three patients treated at 340 mg m(-2) day(-1). CTCg III dizziness was noted in one out of three patients at 250 mg m(-2) day(-1). Neurotoxicity developed during the 1-h infusion and persisted for a variable period (maximum 5 h) after infusion. Prophylactic antiemetic drugs appeared to reduce associated vomiting but did not prevent ataxia. No antiproliferative toxicities were noted and no anti-tumour responses were documented. Penclomedine pharmacokinetic studies confirmed preclinical evidence of extensive apparent distribution (93 l m[-2]) and rapid clearance (41 l h[-1] m[-2]). Purkinje cell loss has been identified in preclinical models after intraperitoneal administration (O'Reilly et al, 1996a) and further clinical development of penclomedine will focus on oral administration.

Having your work published in a good journal is the life-blood of research. Publications are the key element in scientific communication and influence future funding and cancer development for the authors. Every year more and more manuscripts are submitted and competition for acceptance is fierce. The editors of EJC recently held a workshop to discuss ways to improve manuscript writing, and this paper summarises their recommendations. Choose a title carefully, keep the introduction short, avoid confusing methods with results, and use figures wherever possible. Discuss only the relevance of new findings to published literature. Above all read the specific "instructions to authors" -- it is surprising how often this is ignored -- at peril!

6Boehnnger Mannheim, Italv Summary Background: Early clinical trials have suggested that glutathione (GSH) offers protection from the toxic effects of cisplatin. Patients and methods: One hundred fifty-one patients with ovarian cancer (stage I-IV) were evaluated in a clinical trial of cisplatin (CDDP) ± glutathione (GSH). The objective was to determine whether GSH would enhance the feasibility of giving six cycles of CDDP at 100 mg/m2 without dose reduction due to toxicity. Results: When considering the proportion of patients receiving six courses of CDDP at any dose, GSH produced a significant advantage over control - 58% versus 39%, (P = 0.04). For these patients there was a significant difference between the reduction in creatinine clearance for GSH treated patients compared with control - 74% versus 62% (P = 0.006). Quality of life scores demonstrated that for patients receiving GSH there was a statistically significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As an indication of overall activity, these patients were statistically significantly more able to undertake housekeeping and shopping. Clinically assessed response to treatment demonstrated a trend towards a better outcome in the GSH group (73% versus 62%) but this was not statistically significant (P = 0.25). Conclusions: The results demonstrate that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient's quality of life is improved.

Lung cancer, the most prevalent cancer in the western world, is predominantly caused by smoking and thus perceived as a "self-inflicted" disease. Nevertheless, only 20% of smokers develop lung cancer. This review examines the concept of high-risk populations and screening. It looks at developments in the molecular epidemiology of the disease that shed new light on genetic changes that may predispose individuals to malignancy. Improvements in existing drug therapy are discussed as well as important new therapeutic developments, including antigrowth factors (antagonists G and D), antimetastatic agents (matrix metalloproteinase inhibitors), and natural products, arising from a greater understanding of signal transduction pathways and the process of cell metastasis.

nGlaxo Research and Development Limited, Greenford, Middlesex, U.K. Summary Background: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O+D) with metoclopramide plus dexamethasone plus lorazepam (M+D+L) over three consecutive courses of cisplatin chemotherapy. Patients and methods: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4mg bd orally. M + D+L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M+D+L). Results: On the first course of chemotherapy, O + D was significantly superior to the M+D+L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P" 0.014). This was maintained over the three treatment cycles; 38% of O+D and 20% of M+D+L patients remained free of emesis (P — 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O+D group (48%) than in the M+D+L (26%, P - 0.003). The most commonly occurring adverse events in the O+D group were constipation (25%) and headache (19%). In the M+D+L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M+D+L group. Despite the inclusion of lorazepam, 14% of patients in the M+D+L group were withdrawn from the study due to extrapyramida l symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. Conclusion: This study shows that O+D is significantly more effective and better tolerated than M+D+L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.

PURPOSE To determine the maximum-tolerated dose (MTD) and toxicity of PSC 833 infusion administered with etoposide for 5 days in patients with cancer, and to determine the effect of PSC 833 on etoposide pharmacokinetics. PATIENTS AND METHODS Thirty-five patients were entered onto the study, one of whom was ineligible. Etoposide was delivered from day 1 as a 2-hour infusion over 5 consecutive days at a dose of 75 to 100 mg/m2/d. PSC 833 was administered from day 2 as a 2-hour loading dose and as a 5-day continuous infusion. Doses were escalated from 1 to 2 mg/kg (loading dose) and 1 to 15 mg/kg/d (continuous infusion). RESULTS Thirty-four patients were treated with 53 cycles of PSC 833 and etoposide. Steady-state blood PSC 833 levels more than 1,000 ng/mL were achieved in all patients treated at PSC 833 doses > or = 6.6 mg/kg/d by continuous infusion. Myelosuppression was the most common toxicity. The major dose-related toxicity of PSC 833 was reversible hyperbilirubinemia, which occurred in 83% of cycles. The dose-limiting toxicity of PSC 833 was severe ataxia, which occurred in two of nine patients treated at 12 mg/kg/d and in both of the single patients treated at 13.5 and 15 mg/kg/d. PSC 833 concentrations more than 2,000 ng/mL resulted in an increase in etoposide area under the curve (AUC) of 89%, a decrease in etoposide clearance (Cl) of 45%, a decrease in volume of steady-state distribution (Vss) of 41%, and an insignificant increase in alpha half-life (t 1/2 alpha) and significant increase of beta half-life (t 1/2 beta) of 19% and 77%, respectively. CONCLUSION PSC 833 can be administered in combination with etoposide with acceptable toxicity. The recommended continuous infusion dose of PSC 833 for this schedule is 10 mg/kg/d over 5 days. PSC 833 results in an increase in etoposide exposure and etoposide doses should be reduced in patients receiving PSC 833.

Thirty-seven eligible patients with advanced non-Hodgkin’s lymphoma of low-grade, T-cell intermediate- and high-grade histology were treated with pentostatin (2′-deoxycoformycin, dCF) 4 mg/m2 i.v. weekly for 3 weeks and then every 14 days to be followed after 3 doses by the same dosage every 4 weeks until maximum response or progression. Only patients with no more than two chemotherapy regimens were entered in this trial. All patients had measurable disease, performance status of 1, 0 and 2 and adequate bone marrow, renal and liver function. Five of 37 eligible patients experienced a partial response of 8 months’ median duration (range 7–12). The response rate was 17% in low-grade, 8% in T-cell intermediate- and high-grade and 14% in cutaneous T cell lymphoma. The only eligible patient with Hodgkin’s disease underwent progression while on treatment. One case presented with grade 3 leukopenia and another one died of septicaemia, possibly treatment-related. Elevated but reversible creatinine levels were observed in 13% of patients and conjunctivitis in 7%. The toxicity of dCF at this low-dose schedule was acceptable, but the therapeutic activity in pretreated patients with low-grade, T-cell intermediate- and high-grade and cutaneous T-cell lymphomas was limited.

Interferons (IFNs) augment the effect of some antitumor agents, including cis-diamminedichloroplatinum(II) (cDDP), in experimental systems. The effect of human recombinant interferon-alpha 2b (rIFN alpha) on the cDDP-dependent growth delay of a human non-small cell lung cancer established as a xenograft in nude mice (NX002) has been investigated. IFN (10(5) IU/mouse, s.c.) as a single agent had no effect on the growth of the xenograft. cDDP (4.2 mg/kg, i.p.) caused a specific growth delay of 0.42, and this delay was significantly enhanced (to 1.08) by concomitant dosing with the otherwise inactive IFN. Possible mechanisms for this supra-additive relationship between IFN and cDDP have been investigated: increased intratumoral accumulation of platinum was seen at late time points (maximally at 36 hr) during the pharmacokinetic beta-phase of cDDP elimination from the plasma of the nude mice. Tumor:plasma platinum concentration ratios at 36-48 hr indicated significantly increased accumulation of platinum in tumors from IFN-treated mice compared to controls (p0.05). Scheduling experiments suggest that this IFN-mediated effect can persist for 4 hr. These differences may account for the enhanced antitumor activity of cDDP when coadministered with IFN.

Thirty-seven eligible patients, median age 59 years (range 37-72) and median performance status 1 (0-2), with advanced, untreated, measurable gastric carcinoma were given docetaxel, 100 mg m-2 i.v. over 60 min without premedication, once every 3 weeks. Metastatic sites included the liver in 12 patients and retroperitoneal lymph nodes in 16. Eight of the 33 evaluable patients (24%) achieved a partial remission for a median of 7.5 months (3-11+). An additional 11 patients had stabilisation of disease. The patients received a median of four cycles of docetaxel (range 1-8) for a total of 156 courses. Dose reduction was necessary in 30 cycles; 14 cycles were delayed a mean of 3 days. Haematological toxicity consisted mainly of non-cumulative neutropenia, with a median nadir count of 0.35 x 10(9) l-1 (0.04-1.64) and eight episodes (5%) of leucopenic fever; non-haematological toxicities included alopecia, mild nausea and vomiting and allergic manifestations such as skin rash and pruritus. There were no drug-related deaths. Our data indicate that docetaxel is an active agent in advanced gastric cancer; further clinical investigations seem warranted.

50 postmenopausal women with advanced breast cancer were treated with 4-hydroxy-androstenedione (4-OHA) by intramuscular injection of 500 mg given every 2 weeks for 24 weeks unless progression of disease or intolerable side-effects precluded further treatment. All patients had received prior chemotherapy or hormone therapy and 16 patients had responded to their most recent treatment. 46 patients were evaluable for efficacy; 1 died of progressive disease within 3 weeks and 3 were withdrawn for unrelated medical conditions and were ineligible for assessment. All 50 patients were evaluated for toxicity; systemic symptoms were uncommon but 10 patients reported buttock discomfort. Of the 46 patients assessable for response, 7 (15%) had a partial response and 12 (26%) stable disease with 27 (59%) showing disease progression. The median duration of response was 85 weeks (range 32–219 weeks) and the median time to progression was 12 weeks (range 2–219 weeks).

‘What are the mechanisms of intrinsic drug resistance in solid tumours, and how might they be circumvented?’ These are key questions for molecular oncologists, for clinicians and patients. For many years, it was assumed that the interaction of a DNA damaging drug with its target would yield a lethal lesion, and that determinants of intrinsic drug resistance should therefore be sought upstream of this interaction, in drug metabolism or drug transport mechanisms. It is now apparent that cellular responses in vitro to a given DNA lesion can include necrosis, mitotic catastrophe, apoptosis, prolonged cell cycle arrest or even unrestrained growth. The response depends on the cellular genotype and, specifically, on the integrity of response pathways downstream of the drug–target interaction. Despite this progress in the laboratory, the proof that downstream events determine therapeutic responses in the clinic remains elusive. A seminal series of papers from Scott Lowe’s laboratory represent a major step in this direction. Lowe and colleagues prove conclusively that downstream determinants of apoptosis profoundly influence the response to therapy in vivo. They also demonstrate, for the first time, that prolonged drug induced growth arrest can result in prolonged disease stability whilst providing a residual pool of viable malignant cells from which late relapsing clones may ultimately emerge. These papers have mapped out new challenges and new opportunities for the oncologist of the future. Utilising the Em-myc transgenic murine model of B-cell lymphoma (in which myc overexpression drives lymphomagenesis), Lowe and colleagues have developed a rapid technique for the introduction of defined compound genetic lesions, allowing study of resulting phenotypes in a well-controlled fashion in vivo [1]. Primary lymphoma or haematopoetic stem cells, isolated from mice of known genetic background (Em-myc crossed with P53-null, or ARF-null or ARF/INK4a-null), are retrovirally transduced ex vivo with a gene of interest and reintroduced into the tail veins of syngeneic recipients. The transduction process itself does not alter the subsequent behaviour of the resulting lymphoma, so that controls transduced with the green fluorescent protein (GFP) gene alone yield lymphomas histopathologically indistinguishable from the parent lymphoma. Introduction of a gene of interest along with GFP in a bicistronic retroviral vector allows study of the effect of that gene on tumour behaviour by the elegant non-invasive means of whole-animal fluorescence imaging. An early paper in the series demonstrates conclusively that overexpression of the anti-apoptotic protein bcl-2 produces a multi-drug resistance phenotype in primary lymphomas in vivo [2]. This effect is suppressed by prior serial passage of the lymphoma lines in vitro, because the cells acquire multi-drug resistance merely as a consequence of prolonged cell culture. Furthermore, the effect of bcl-2 is completely obscured in standard clonogenic assays of drug sensitivity, because bcl-2 suppresses drug-induced apoptosis, but not prolonged growth arrest, both equally efficient means of reducing clonogenicity. These observations shed some light on why assays of drug response in established cell lines or xenografts derived from solid tumours have failed in the past to consistently predict clinical response, and indeed have often provided contradictory results. In general, such models simply cannot recapitulate conditions pertaining in vivo.

Background: The purpose of the study was to determine the prevalence and associations of clinically relevant fatigue (CRF) in men with biochemically controlled prostate cancer on long-term androgen deprivation therapy (ADT). Patients and methods: One hundred and ninety-eight men were surveyed and the prevalence of CRF (Brief Fatigue Inventory score >3) determined. Associations with other measures (Hospital Anxiety and Depression Scale; International Prostate Symptom Score; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; Brief Pain Inventory worst pain; clinical and demographic information) were explored in univariate and multivariate analyses. Results: Eight-one per cent (160 of 198) of questionnaires were analysable. CRF prevalence was 43% (68 of 160). CRF associations included moderate/severe urinary symptoms, anxiety and medical co-morbidities; the strongest associations were depression [odds ratio (OR) 9.8, 95% confidence interval (CI) 4.3-22.8] and pain (OR 9.2, 95% CI 4.0-21.5). After controlling for other factors, the independent associations were depression (OR 4.7, 95% CI 1.6-14.0) and pain (OR 3.1, 95% CI 1.0-8.9). There was no association with age, disease burden or treatment duration. Conclusions: Two-fifths of men with biochemically controlled prostate cancer on long-term ADT report CRF that interferes with function. Management aimed at improving CRF should address depression and pain. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Traditionally, medical oncology has focused on the active period of diagnosis, treatment and follow-up of cancer patients, and palliative medicine, the pre-terminal and end-of-life phases. Palliative medicine physicians have particular expertise in communication and symptom control, especially, for example, with pain management. Medical oncologists also have need of excellent communication skills and knowledge of supportive care issues, such as the management of emesis, bone marrow suppression, mucositis, neuropathy, and symptoms created by treatment. This article examines the interface between medical oncology and supportive and palliative care to emphasize how each can benefit from the others.

Summary Background The observed activity of cisplatin in breast cancer and its unattractive toxicity profile in palliative treatment warranted further study of platinum analogues in this disease. Patients and methods Sixty-two patients with recurrent or metastatic breast cancer, 61 of whom had been previously treated with chemotherapy, were randomly assigned to therapy with either iproplatin (n = 32) or carboplatin (n = 30). Both platinum analogues were administered intravenously, iproplatin at a dose of 240 mg/m2 every 4 weeks and carboplatin at a dose of 450 mg/m2 every 5 weeks. Results Only two patients responded to iproplatin (7%) for durations of 21 and 61 weeks, and one patient responded to carboplatin (3%) for a duration of 64 weeks. All responses were complete. At the given dose schedules carboplatin was more myelosuppressive than iproplatin. Non-hematologic toxicities included nausea and vomiting (93% vs. 90%), diarrhea (20% vs. 10%) and hemorrhage (16% vs. 10%) for iproplatin and carboplatin, respectively. Two patients developed alopecia with carboplatin. No renal toxicity was observed. Conclusions Both iproplatin and carboplatin have limited activity in previously treated women with advanced breast cancer when given in conventional dosages.

Background: Drug development traditionally has relied upon the complementary contributions of clinicians and scientists at academic institutions and at pharmaceutical companies. Greater regulatory burdens, increased bureaucratic requirements, restricted reimbursement, and spiralling research and development costs are exerting pressure on the drug development pipeline. The result is a de-emphasis of exploratory research, particularly independent academic research, despite its proven value in identifying new drug targets and developing innovative cancer therapies. Design: An expert panel assembled by the Biotherapy Development Association-a nonprofit international forum for academic and industry researchers, patients, and government regulatory and postregulatory agencies-examined the growing schism between academia and industry and identified several causes of declining academic research. Results: The authors propose solutions to sustain investigator-initiated research and provide a new model whereby expert organisations provide a forum for academia and industry to plan studies within a regulatory framework to support licensure/authorisation and reimbursement for new molecularly targeted agents and biomarkers. Conclusions: Investigator-initiated trials have led to the discovery and development of innovative, safe, and effective cancer treatments. To ensure that such research continues, action will be required on the parts of legislative and regulatory bodies, industry, universities, patient advocacy organisations, and preclinical and clinical academic scientists. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Previous studies have demonstrated that is is the local immune response which is of importance for the anti-tumour activity of BCG therapy. We have investigated this by quantitative immunohistochemical analysis of serial bladder mucosal biopsies taken before, during and after an eight week course of intravesical Evans strain BCG therapy and three monthly thereafter in 16 patients (15 extensive CIS and one extensive G2pTa papillary tumour). This particular group of patients had a 67% complete response rate at six months post-treatment. The main findings on immunohistochemical analysis were the universal induction of MHC Class II antigens by urothelial cells which was statistically significant up to 6 months after completion of therapy, coupled with a T cell dominated cystitis. Increases in CD3+ T cell infiltration of the lamina propria and that of the CD4+ "Helper" subset which predominated were significant up to 3 months post-therapy and these cells showed evidence of increased immunological activation as shown by increased interleukin-2 receptor and MHC Class II antigen expression. There were also significant increases in CD68+ macrophage and the incidence of CD22+ B cell aggregates but CD57+ NK cells were sparse both before and after therapy. The degree of mononuclear cell infiltration for all markers examined (except CD57) was significantly greater in those biopsies in which the urothelial cells expressed MHC Class II antigens than in those that did not. Also the degree of T cell infiltration (CD3, CD4 and CD8) was significantly greater in the eight patients deemed to have had a complete response compared to those seven with a partial response or treatment failure. These results are discussed in terms of possible mechanisms of action for BCG therapy and in particular the role of enhanced antigen presentation by tumour cells.

The inhibitory effect of interferon-gamma on the growth of three human bladder cancer cell lines, RT4, RT112 and MGH-U1, representing tumour grades 1, 2 and 3 respectively, was studied. The effects of 10,100 and 1000 Uml.−1 of interferon-gamma on cell numbers and thymidine incorporation were measured at 24hour intervals up to a maximum of seven days. Morphological appearances were also studied.Each line was susceptible to the growth inhibitory effects of interferon-gamma and this was both dose and time dependent. The effects of interferon-gamma, on the RT4 and RT112 cells were apparent from 24hours, and were both cytostatic and cytotoxic in nature, whereas the effects on MGH-U1 cells were seen from 48hours onwards and were only cytostatic. Cytological changes occurred in all three cell lines, being most pronounced in RT112.The growth of bladder cancer cells was inhibited by interferon-gamma, and in this study high grade tumour cells were least sensitive.

The Scottish Melanoma Group (SMG) was established in 1979 to assess mortality from and incidence, features, pathological data, and management of cutaneous malignant melanoma in Scotland. Incidence during the first five years and five-year survival have already been reported. We now have data about incidence and mortality over eleven years in relation to anatomical site and pathological types. From 1979 to 1989, 1354 male and 2459 female patients with primary cutaneous malignant melanomas were first diagnosed in Scottish residents. The incidence rate per 100,000 population per year has increased from 3.4 in 1979 to 7.1 in 1989 for men, and from 6.6 to 10.4 for women. The overall increase over eleven years is 82% (7.4% per year). The greatest rates of increase are seen in lesions of the superficial spreading histogenetic type, arising on the female leg and the male trunk. Following public education programmes started in 1985, the proportion of all melanomas less than 1.5 mm thick has shown a sustained and significant increase. Mortality data for 1661 patients for whom a minimum of five-year follow-up is available shows five-year survival of 71.6% overall (77.6% for women, 58.7% for men). The survival advantage for women persists when appropriate statistical adjustment is made for thickness, ulceration, and histogenetic type. These data are useful in designing public education programmes aimed at both primary and secondary prevention of melanoma and in auditing changes in trends that might result from such education.

46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.

OBJECTIVE--To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN--Randomised double blind crossover study. SETTING--Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS--100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS--Patients were given intravenous dexamethasone (20 mg) or physiological saline with intravenous ondansetron 8 mg before cisplatin, then ondansetron 1 mg/h for 24 hours. Oral ondansetron 8 mg was taken three times daily on days 2-6. MAIN OUTCOME MEASURES--Incidence of complete or major control of emesis (0-2 episodes in the 24 hours after chemotherapy). RESULTS--Complete or major control was obtained in 49 out of 71 (69%) of patients after receiving ondansetron plus dexamethasone compared with 40 out of 71 (56%) when they were given ondansetron alone (p = 0.012). This effect was most pronounced in the first 12 hours after chemotherapy. Patients receiving the combination also had significantly less nausea. Of the 53 patients who expressed a preference, 38 (72%) preferred the combination treatment (p = 0.002) to ondansetron alone. The effect of ondansetron on delayed emesis was less pronounced. CONCLUSIONS--Dexamethasone makes a significant contribution to the efficacy of ondansetron in the control of acute platinum induced emesis.

In a non-randomised study in six centres in the UK, 24 patients with previously untreated small-cell lung cancer of limited extent were treated with a regimen of alternating chemotherapy and radiotherapy to assess response, toxicity, and the feasibility of applying such a regimen on a multicentre basis in the UK. The intention was to give six courses of chemotherapy on five consecutive days at 4-week intervals: etoposide 75 mg m-2 on days 1, 2, and 3; doxorubicin 40 mg m-2 on day 1; cisplatin 100 mg m-2 on day 2; and cyclophosphamide 300 mg m-2 on days 2, 3, 4 and 5. A dose of 20 Gy thoracic radiotherapy was to be given following the 2nd and the 3rd courses, and one of 15 Gy following the 4th course. After 12 patients had been admitted, the cisplatin dosage was reduced to 80 mg m-2 because of unacceptable toxicity. Two patients were withdrawn during treatment on review of their histology because their diagnosis was found to be incorrect. Only one patient of the 12 treated with cisplatin 100 mg m-2 was able to complete treatment, compared with five of the eligible ten given the lower dosage. Among the 22 patients with confirmed small-cell disease, a complete response was reported in 14 (64%) and a partial response in a further three (total response rate 77%). Myelosuppression was the commonest serious adverse effect. It occurred in 19 of the 24 patients and gave rise to septicaemia in five, four of whom were receiving the higher cisplatin dose. Sixteen patients required blood transfusion and ten platelet transfusion. Vomiting, oesophagitis, and peripheral neuropathy occurred in 12, four and four patients, respectively, and radiation pneumonitis developed in two. Treatment was considered a contributory cause of death in four. The working party concluded that the alternating regimen was feasible in only a small proportion of centres in the UK, and decided not to embark on a multicentre randomised trial comparing alternating with conventional scheduling.

33 106 (32%) patients with limited disease (LD) small cell lung cancer (SCLC) achieved a bronchoscopically confirmed complete response (CR) following 4 courses of induction chemotherapy. These patients were offered ‘late intensification’ with high dose melphalan (HDM) (140 mg/m 2 ) and autologous bone marrow support. LDCR patients were advised also to receive radiotherapy to the primary site and prophylactic cranial irradiation (PCI). After a minimum follow-up of 3 years, the LDCR patients who received HDM ( n =13) have had a median disease-free survival (DFS) of 15 months and a median overall survival (OS) of 16 months, compared with a DFS of 9 months ( P =0.06) and OS of 11 months ( P =0.23) for patients who did not receive late intensification ( n =20). Chest radiotherapy and PCI reduced the frequency of recurrence at these sites. Only patients who had received both chest radiotherapy and PCI were disease-free at 18 months. In this non-randomised study it is not possible to state with certainty the contribution of consolidation treatment in SCLC. Nevertheless, in patients with chemosensitive limited disease, late intensification chemotherapy, chest radiotherapy and PCI all appear to have a positive effect on DFS.

In a phase I study the anthrapyrazole biantrazole (Warner-Lambert Company) was given to 41 patients with tumour refractory to existing therapy. The drug was given i.v. weekly for 3 weeks, with a 3-week interval between courses. At the 1st week a full pharmacokinetic study was performed, and at weeks 2 and 3, blood samples were taken at 1 and 6 h following treatment to check for drug accumulation. Biantrazole pharmacokinetics were linear with respect to the AUC (r = 0.924) over the full range of doses studied (4-36 mg/m2) but exhibited large inter-patient variations at each dose level. Elimination was triphasic, comprising two rapid early phases and a long terminal half-life (mean, 14.1 +/- 7.8 h). There was no evidence of drug accumulation over the 3-week treatment period. Approximately 12% of the parent drug was excreted unchanged in the urine together with two non-circulating, more water-soluble metabolites. Biantrazole was well tolerated but did cause moderate emesis at doses of greater than 18 mg/m2 and mild alopecia. The dose-limiting side effect was leucopenia, with no other major toxicity being observed. One patient developed biventricular failure that was not clearly related to biantrazole administration. On the present schedule, the recommended dose of biantrazole is 24 mg/m2. No response were seen in this patient population.

Hormonal therapy has been used erratically to treat epithelial ovarian cancer since the mid 1960s; however, there has been little progress until recently in our understanding of which patients might benefit from treatment. Some clarity in the field is now beginning to emerge from recent studies, which have started to define biomarkers within epithelial ovarian cancers that link with hormonal response and thereby indicate which cohort of patients might be amenable to hormonal treatment.Oestrogen-deprivation therapy in the form of the aromatase inhibitor letrozole has demonstrated activity in three clinical studies. As only a minority of patients will benefit from hormonal approaches, recent efforts have focussed on the use of molecular markers to help identify which subgroup of patients might respond to treatment. Parallel laboratory studies using primary cancer material for which endocrine response is known and model-based findings have identified components of oestrogen signalling pathways that may help predict outcome.Use of the antioestrogen letrozole in ovarian cancer has consistently demonstrated a significant level of activity and the larger clinical studies have linked response with oestrogen receptor alpha expression and other biomarkers.

Purpose: Plitidepsin, given as a 1-hour weekly i.v. infusion for 3 consecutive weeks during a 4-week treatment cycle, was investigated in patients with solid tumors to determine the maximum tolerated dose and the recommended dose (RD) using this administration schedule. Experimental Design: Consecutive cohorts of patients with metastatic solid tumors or non–Hodgkin's lymphomas were to be treated at escalating doses of plitidepsin in a conventional phase I study including pharmacokinetic analyses of plitidepsin in plasma, whole blood, and blood cell pellets. Results: Forty-nine patients with solid tumors were enrolled, and 48 were treated with plitidepsin (doses from 0.133 to 3.6 mg/m2/week). Dose-limiting toxicities (defining 3.6 mg/m2/week as the maximum tolerated dose) included myalgia, increased creatine phosphokinase levels, and sustained grade 3/4 increases of hepatic enzyme levels. The RD was established at 3.2 mg/m2/week. The most common toxicities were fatigue, vomiting/nausea, anorexia, injection site reaction, and pain, mostly of mild or moderate severity. Muscular toxicity manifested by mild-moderate myalgia, weakness, and/or creatine phosphokinase elevations occurred in ∼25% of patients and seemed to be dose related. Transient transaminase elevations were frequent but achieved grade 3 or 4 in only ∼10% of patients. Plitidepsin lacked significant hematologic toxicity. No complete or partial tumor responses were observed; however, five patients had disease stabilization (including one patient with medullary thyroid carcinoma with an unconfirmed partial response and one patient with renal carcinoma with major tumor shrinkage in lung metastases). Pharmacokinetic results for the RD indicated a long plasma half-life give value (16.8 ± 7.7 hour) and a high volume of distribution value (525.2 ± 219.3 L). Conclusions: The recommended dose for plitidepsin given as a weekly 1-hour schedule was 3.2 mg/m2/week. Muscular and liver toxicity were dose limiting at 3.6 mg/m2/week. Additional evaluation of this dose dense schedule is warranted.

Modern palliative care started with St Christopher's Hospice in 1967 and was initially regarded as 'terminal care'. This served as a template for a developing model of multidisciplinary clinical care, teaching and research. A decade later, several hospital Palliative Care Teams were established and different terms were used to describe them. An evidence base developed slowly and a medical subspeciality was established, known as Palliative Medicine. Over the last two decades we have seen an expansion in non-hospice palliative care. The terms used to describe this care have been variable and inconsistent. Our challenges in progress involve establishing clear terminology and an evolving improved evidence base, along with a realisation that there are large gaps in patient care.

Summary Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cytotoxic drugs. We have performed a phase II study of cisplatin (100 mg/m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (11/24) of patients with squamous carcinoma responded and an overall partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neurological toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.

Between 1975 and 1984, 125 cases of histologically confirmed soft tissue sarcomata (STS) were registered in the Department of Clinical Oncology in Edinburgh. Of these, 100 were eligible for analysis of prognostic factors. The overall 5-year survival rate was 21.5%. Univariate analysis demonstrated that extent of surgery, radical versus palliative or no radiotherapy, mass as a presenting symptom, metastases at presentation, site, histological type, mitotic activity, grade and UICC stage all had a statistically significant effect on survival. Analysis using the proportional hazard regression model was performed on the 87 patients for whom all variables were recorded. When all histological and clinical features and treatment modalities were included in the model then radiotherapy, surgery, necrosis, sex and mitoses were identified as independent prognostic variables. When symptoms and treatment were excluded then the multivariate analysis identified sex and mitotic activity as independent parameters. For the 33 superficial STS with tumour size recorded multivariate analysis revealed size, necrosis and cellularity as independent prognostic variables. For the 31 deep STS histological type, sex, surgery and radiotherapy were identified as independent prognostic parameters.