Secondary non-Hodgkin lymphoma of the ethmoid sinus after temozolomide.

The paranasal sinuses are rarely the site of malignancy, especially non-Hodgkin lymphoma. In such cases, the ethmoid sinus is the second most frequently involved paranasal sinus. Diagnosis of these malignancies is difficult because the early symptoms often mimic benign sinus pathology. Thus, most cases are diagnosed at an advanced stage, and their prognosis is poor. Here we describe the case of a 58-year-old man with a secondary high-grade B-cell non-Hodgkin lymphoma of the ethmoid sinus. This malignancy was diagnosed two years after the patient had received treatment with temozolomide for a glioblastoma multiforme. This case highlights that malignant tumours of the paranasal sinuses should always be included in the differential diagnosis of sinus disease. Additionally, patients treated with temozolomide should receive regular follow-up care including vigilant evaluation for secondary tumours, such as non-Hodgkin lymphoma.

Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma.

BACKGROUND: To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy. PATIENTS AND METHODS: In this two-arm, open-label, phase II study patients were stratified according to their epidermal growth factor receptor (EGFR) gene amplification status. Cetuximab was administered intravenously at a dose of 400 mg/m(2) on week 1 followed by weekly dose of 250 mg/m(2). The primary end point for this study was the response rate in both study arms separately. RESULTS: Fifty-five eligible patients (28 with and 27 without EGFR amplification) tolerated cetuximab well. Three patients (5.5%) had a partial response and 16 patients (29.6%) had stable disease. The median time to progression was 1.9 months [95% confidence interval (CI) 1.6-2.2 months]. Whereas the progression-free survival (PFS) was <6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of >9 months. Median overall survival was 5.0 months (95% CI 4.2-5.9 months). No significant correlation was found between response, survival and EGFR amplification. CONCLUSIONS: Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015.

BACKGROUND: The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI: irinotecan (180 mg/m(2) i.v. on days 1, 15 and 22); FA (200 mg/m(2) i.v. on days 1, 2, 15, 16, 29 and 30); 5-FU (400 mg/m(2) i.v. bolus, then 22-h, 600 mg/m(2) infusion) or CAPIRI: irinotecan (250 mg/m(2) i.v. infusion on days 1 and 22); capecitabine p.o. (1000 mg/m(2) b.i.d. on days 1-15 and 22-36). Patients were additionally randomly assigned to receive either placebo or celecoxib (800 mg: 2 x 200 mg b.i.d.). RESULTS: The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months). CONCLUSION: Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI.

A Belgian registry of interleukin-2 administration for treatment of metastatic renal cell cancer and confrontation with literature data.

In an effort to map the use of interleukin-2 (IL-2) treatment in patients with clear cell renal cell cancer (RCC) in Belgian hospitals, 44 cases were registered from 9 hospitals between February 2003 and June 2006. It was demonstrated that the majority of these patients were treated with subcutaneous (SC) IL-2. Other methods such as the inhalation of the drug in case of intrathoracic disease or high dose intravenous (IV) administration were much less frequent (3 and 0 cases in this registry, respectively). The results of antitumour activity (around 16% partial response-absence of complete responses) and toxicity of this drug correlate with observations from the literature with the SC administration. In view of the poor results and tolerance with the currently used cytokines (IL-2 or interferon-alfa), much hope is directed towards the development of the novel targeted drugs like sunitinib or sorafenib used alone or in combination with cytokines in this disease.

Optimisation of irinotecan dose in the treatment of patients with metastatic colorectal cancer after 5-FU failure: results from a multinational, randomised phase II study.

Although irinotecan 350 mg m(-2) is a standard option for relapsed/refractory advanced colorectal cancer, there is some evidence that suggests that a higher dose may be more effective, with acceptable tolerability, following 5-fluorouracil (5-FU). This study assessed the optimal dosing strategy for irinotecan, along with treatment efficacy and safety. A total of 164 patients with metastatic colorectal cancer progressing after failure on 5-FU or raltitrexed received either 350 mg m(-2) irinotecan (Group A; n=36) or 250, 350 or 500 mg m(-2), according to individual patient tolerance (Group B; n=62) or based on risk factor optimisation (Group C; n=66). There were no complete responses. There was a trend towards a higher overall response rate in Group B (13%) than in Groups A (8%) and C (9%). Tumour control growth rate was high in all three groups: 58% in group A, 60% in Group B and 50% in Group C. A total of 34% of patients in Group B and 9% in Group C were able to receive a dose of 500 mg m(-2). Median duration of response and time to progression were significantly longer in Groups A and B compared with Group C. No significant between-group differences for any adverse events were seen, although there was a small trend towards better tolerability in Group B. Individual dose escalation based on patient tolerance may allow more patients to receive a higher irinotecan dose without causing additional toxicity and can be an appropriate patient management strategy.

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study.

PURPOSE: To determine the safety profile and activity of the combination of docetaxel, cisplatin and 5-fluorouracil (5-FU) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days. Cycles were planned every 3 weeks up to four cycles, whereafter the patients were treated with locoregional radiotherapy. Two dose levels were studied. Doses in level I were 75 mg/m(2) of docetaxel, 75 mg/m(2) of cisplatin and 750 mg/m(2)/day of 5-FU; in level II the cisplatin dose was escalated to 100 mg/m(2). Following chemotherapy, all patients were to receive curative radiotherapy according to the standards in the different institutions. RESULTS: Twenty-five patients were treated at dose level I with 86 cycles (median four; range one to four), and 23 at dose level II with 84 cycles (median four; range two to four). The median relative dose intensity was 0.99 (range 0.86-1.04) at level I and 0.94 (range 0.79-1.02) at level II. The response rate in the intention-to-treat population was 64% [95% confidence interval (CI) 42.5% to 82%] in level I and 78.3% (95% CI 56.3% to 92.5%) in level II; all were partial responses. The maximum tolerated dose was reached at level II with renal toxicity, nausea, stomatitis and thrombocytopenia as principal dose-limiting toxicities. The median survival of the 48 patients was 18.5 months. The survival at 12, 18, 24 and 30 months was 69, 54, 41 and 31%, respectively. CONCLUSIONS: The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.

Comparison of modified technetium-99m albumin and technetium-99m red blood cells for equilibrium ventriculography.

UNLABELLED: A newly developed modified form of 99mTc-labeled human serum albumin reconstituted from a kit (99mTc-dimercaptopropionyl-human serum albumin; 99mTc-DMP-HSA) was prospectively compared to 99mTc-labeled red blood cells (RBC) in patients referred for equilibrium radionuclide ventriculography at rest to evaluate its potential use as a blood-pool imaging agent. METHODS: A Paired comparison between 99mTc-DMP-HSA and either in vitro or in vivo 99mTc-labeled RBC was performed within 2 days in 20 patients'. For each study, two sets of images were acquired, starting at 15 min and 180 min postinjection, respectively. Each set consisted of a gated blood-pool cardiac study and a planar static image centered on the patient's thorax. All data were processed by two independent observers. Early and late postinjection parameters were calculated: ejection fraction (EF) value, activity within the main organs surrounding the left ventricle (LV), ratio of activity between the LV and these surrounding organs for each study separately, and temporal (late/early) evolution of the intraorgan activities and of the LV/organ ratios after decay correction. RESULTS: The images and the visual wall-motion analysis were of good quality with both agents in most patients, without significant image degradation at 180 min postinjection. Calculated EF values were highly comparable with the two tracers. Interobserver variability was 0.17% (RBC) and 1.08% (DMP-HSA) for the early EF value (EF1), and 0.62% (RBC) and 0.27% (DMP-HSA) for the late EF (EF2). Mean difference between EF2 and EF1 was 0.74% (Observer 1) and 0.28% (Observer 2) for 99mTc-RBC, and -2.88% (Observer 1) and -2.07% (Observer 2) for 99mTc-DMP-HSA. When comparing 99mTc-DMP-HSA to 99mTc-RBC the mean difference was 1.27% (Observer 1) and 0.36% (Observer 2) for EF1, and -2.35% (Observer 1) and -1.99% (Observer 2) for EF2. Also, the biodistribution and temporal evolution of the organ repartition of both compounds were stable and similar, with values of late/early activity ratios very close to one for all the studied organs [mean intraorgan ratio: 0.946 for 99mTc-RBC (range: 0.881-1.086) and 0.979 for 99mTc-DMP-HSA (range: 0.914-1.141); mean late/early LV/organ ratio: 0.964 for 99mTc-RBC (range: 0.919-1.016) and 0.967 for 99mTc-DMP-HSA (range: 0.912-1.035)]. CONCLUSION: Paired comparison of kit-prepared 99mTc-DMP-HSA to 99mTc-labeled RBC demonstrated that both agents were very closely related regarding as well the calculated EF value as the in vivo stability up to more than 3 hr postinjection. Technetium-99m-DMP-HSA may constitute a practical and useful replacement for 99mTc-labeled RBC.

Role of hepatic arterial embolisation in the treatment for metastatic insulinoma. Report of two cases and review of the literature.

Malignant insulinomas are very rare. They have typical clinical and biochemical characteristics that allow an early detection and distinction from other sorts of islet cell carcinoma. As a result a curative resection can occasionally be managed. Nevertheless, for more advanced stages the same treatment options as for other metastatic neuroendocrine tumours must be considered: palliative surgery, medical treatment, chemotherapy and hepatic arterial (chemo-) embolisation. Especially the last kind of treatment has recently gained interest. We report two cases of metastatic insulinoma treated in this way. In the first case we are able to record an unusually long survival through the single use of sequential embolisation, following palliative resection of the primary tumour. In the second case we describe the current way to use this technique, i.e. in combination with chemotherapy. We argue that it might be more important in the treatment of metastatic insulinoma to combine hepatic arterial embolisation with other types of local or systemic therapy, rather than the choice of this most efficient technique on its own.

Pituitary metastasis mimicking a pituitary adenoma. A description of two cases.

The cases of two elderly women treated for temporal hemianopsia due to a large pituitary mass with suprasellar extension are presented. In both cases, the clinical picture, without diabetes insipidus and cranial nerve paralysis, as well the neuroimaging and endocrinological investigation showing hypopituitarism, were suggestive of a non-secreting pituitary adenoma. In the first patient malignant tissue was unexpectedly encountered during transsphenoidal surgery. Anatomopathological investigation confirmed the presence of a metastasis of a breast carcinoma for which she had been treated 17 years earlier. In the second patient, a preoperative chest X-ray before transsphenoidal surgery revealed an asymptomatic bronchial tumour. Subsequently a squamous cell carcinoma with a metastasis in the pituitary was confirmed. These two cases illustrate the fact that a pituitary metastasis can closely mimic a pituitary adenoma. Even in the absence of suggestive symptoms such as diabetes insipidus and/or cranial nerve paralysis the possibility of metastatic disease in the differential diagnosis of a pituitary mass should always be considered.

Changes in arterial oxygen tension after gastric lavage for drug overdose.

1. Changes in arterial oxygen tension after gastric lavage were investigated in a prospective study of 55 patients admitted for drug overdose. 2. A significantly greater decrease was observed in smokers compared to non-smokers. 3. A correlation was found between the tricyclic antidepressant serum level and the observed oxygen tension decrease. 4. The usefulness, as well as the safety of the lavage procedure, in managing tricyclic antidepressants overdoses is controversial.