Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy.

An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle (dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter randomized phase II study assessed the efficacy and safety of two different approaches: epirubicin 110 mg/m(2) combined with paclitaxel 200 mg/m(2) every 21 days and epirubicin 75 mg/m(2) combined with paclitaxel 175 mg/m(2) every 10 days, both supported with G-CSF. Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade ≥ 3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dose-dense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic) cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194 and 448/1045 mg/m(2), treatment durations were 126 and 61 days, and delivered dose intensities were 36/67 and 51/120 mg/m(2)/week for the dose-escalated and dose-dense arm, respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months, respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time, but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The value of dose-densification over standard scheduled chemotherapy regimes yet needs to be determined.

Heterophilic antibodies may be a cause of falsely low total IGF1 levels.

BACKGROUND: A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions. CASE: A 56-year-old man was referred with a decline in physical performance, unexplained osteopenia, and weight loss of 3 kg over the past 8 months. Although clinical signs and symptoms were unremarkable, laboratory results pointed to secondary hypothyroidism and secondary hypogonadism. In addition, the serum total IGF1 level (CLIA; Siemens Medical Solutions Diagnostics) was in the low normal range. Two GH stimulation tests were performed, but these tests did not support the diagnosis GHD. Moreover, IGF1 bioactivity measured by the kinase receptor activation assay was normal. Interference of heterophilic antibodies was considered. After pretreatment with specific heterophilic blocking tubes that contain blocking reagents to eliminate heterophilic antibodies, serum-free thyroxine, testosterone, and IGF1 levels turned out to be normal. CONCLUSION: To the best of our knowledge, we here describe the first case in the literature of a patient with low serum total IGF1 levels due to interference from heterophilic antibodies in the used IGF1 immunoassay. When confronted with low-IGF1 levels that do not fit the clinical picture, interference of heterophilic antibodies should be considered in the differential diagnosis.

Monoarthritis of the elbow due to metastatic colon carcinoma: diagnosis based on the presence of adenocarcinoma cells in synovial fluid.

There are many diseases that can cause monoarthritis, malignancy being one of the more rare causes. We present such a case and discuss the relationship between malignancy and arthritis. Typically a large joint is involved, most frequently the knee and very rarely the elbow. The value of cytological examination of synovial fluid is stressed. Synovial fluid in malignant joint disease is usually sanguineous and not consistent with an inflammatory process. Synovial fluid analysis can avoid a biopsy of bone or synovium and lead to an early diagnosis and palliative treatment.

[Diagnostic image (349). A woman with flushes]. / Diagnose in beeld (349). Een vrouw met opvliegers. Carcinoïd van het ovarium.

A 57-year-old woman suffered from frequent flushes due to an ovarian carcinoid tumour.

Randomised Phase III study of biweekly 24-h infusion of high-dose 5FU with folinic acid and oxaliplatin versus monthly plus 5-FU/folinic acid in first-line treatment of advanced colorectal cancer.

BACKGROUND: A phase III study was started to compare oxaliplatin/5FU/LV in the first-line with bolus FU/LV in metastatic colorectal cancer. PATIENTS AND METHODS: 302 patients were randomised and received bolus 5-FU 425 mg/m(2) day 1-5, FA 20 mg/m(2) day 1-5, q 4 wk or oxaliplatin 85 mg/m(2), 2 h-infusion, FA 200 mg/m(2), 1-h infusion. 5-FU 2600 mg/m(2), 24-h infusion day 1, q 2 wk. The primary endpoint was response rate (RR). RESULTS: The median follow-up is 31.8 months, 90.4% of the patients have died. Confirmed RR, progression free survival (PFS; months) and median overall survival (OS; months) in 5FU/LV versus 5FU/LV/oxaliplatin were respectively 18.5% versus (vs) 33.8% (P = 0.004), 5.6 vs 6.7 (P = 0.016) and 13.3 vs 13.8 (P = 0.619). In the 5FU/LV/oxaliplatin arm less grade (3/4) toxicity was measured for diarrhoea, stomatitis, an increase in idiosyncratic side effects and neurosensory events compared with 5FU/LV. The quality of life (QOL) was equal in both arms. Second line treatment was given in 62% of the patients, crossover of 5FU/LV to 5FU/LV/oxaliplatin occurred in 14%. CONCLUSIONS: Oxaliplatin in the first-line resulted in an increased RR and PFS with less grade 3/4 mucositis/diarrhoea compared with 5FU/LV alone. Idiosyncratic side effects deserve attention with oxaliplatin. Despite a low treatment cross over rate, OS in both groups was comparable.

[Delayed recognition of falciparum malaria from a non-endemic region in the Dominican Republic]. / Laat herkende malaria tropica uit een niet-endemisch gebied in de Dominicaanse Republiek.

A 28-year-old patient had suffered from fever, headache, abdominal pains and vomiting for the past three weeks. She had visited a region in the Dominican Republic where the risk of malaria is considered to be low. The complaints were initially regarded as a viral infection. Later, however, she was found to have severe falciparum malaria. She recovered completely following antibiotic therapy. Since November 2004, 17 cases of falciparum malaria have been reported world-wide among travellers to non-endemic regions in the Dominican Republic. Physicians should always consider the possibility of malaria in travellers because a timely diagnosis of falciparum malaria can be of vital importance.

Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer.

Satraplatin is a novel oral platinum (IV) complex that shows activity against hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor lines in phase I and phase II trials. A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC. After 50 randomized patients, the trial was closed to further accrual by the sponsoring company. An ad hoc analysis of all available data is reported here. Eligibility criteria included pathological proof of prostate cancer, documented progression despite prior hormonal manipulation, WHO PS 0-2, and no daily intake of narcotic analgesics. Patients were randomized between satraplatin 100 mg/m(2) for 5 days plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent. 48/50 patients have progressed and 42 have died, mostly due to prostate cancer. Median overall survival was 14.9 months (95% CI: 13.7-28.4) on the satraplatin plus prednisone arm and 11.9 months (95% CI: 8.4-23.1) on prednisone alone (hazard ratio, HR = 0.84, 95% CI: 0.46-1.55). A >50% decrease in prostrate specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free survival was 5.2 months (95% CI: 2.8-13.7) on the satraplatin plus prednisone arm as compared to 2.5 months (95% CI: 2.1- 4.7) on the prednisone alone arm (HR = 0.50, 95% CI: 0.28-0.92). This difference is statistically significant (p = 0.023). Toxicity was generally minimal in both arms. This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination. Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting.

A phase I dose-escalating study of docetaxel plus folinic acid and 5-fluorouracil in anthracycline-pretreated patients with metastatic breast cancer.

BACKGROUND: Since the need for nonanthracycline-containing chemotherapy regimens increases with the increased use of anthracyclines in earlier stages of breast cancer, we investigated the feasibility of the combination of docetaxel and 5-fluorouracil (5-FU) with folinic acid (FA). PATIENTS AND METHODS: Anthracycline-pretreated patients with metastatic breast cancer were eligible. Docetaxel was administered as a one-hour infusion every three weeks on day 1, FA 500 mg/m2 (fixed dose) as a two-hour infusion on days 1 and 15 and 5-FU as a 24-hour infusion on days 1 and 15. The dose levels tested were (docetaxel/5FU in mg/m2): 60/1800, 75/1800, 85/1800, 100/1800, and 100/2100. RESULTS: Altogether 28 patients were accrued and treated in this multicentre open-label study. Dose-limiting toxicities (DLTs) were not observed at dose level I, and in two patients in each of the higher dose levels. DLTs observed were grade III/IV infection (n=4), febrile neutropenia (n=2), diarrhoea (n=1) and erythema (n=1). Partial responses were observed in 10 out of 24 evaluable patients (42%, 95% confidence interval 22.1 to 63.4%). Dose escalation beyond the highest dose level (100/2100) was deemed inappropriate, because these dose levels correspond to recommended dose levels for each drug as a single agent. CONCLUSION: Combination of docetaxel (100 mg/m2, one-hour infusion q3 weeks on day 1), FA (500 mg/m2, two-hour infusion on days 1 and 15) and 5-FU (2100 mg/m2, 24-hour infusion on days 1 and 15) is a feasible regimen with encouraging activity in anthracycline-pretreated patients.

[Metabolic disregulation after starting feeding: "refeeding" syndrome: the central role of phosphate]. / Metabole ontregeling na opnieuw beginnen met voeding: 'refeeding'-syndroom; de centrale rol van fosfaat.

A 47-year-old man was admitted due to serious weight loss after several months in which he had not eaten and had drunk almost solely beer. Shortly after the start of enteral tube feeding, the patient developed serious heart failure. This was associated with severely disrupted electrolyte levels and in particular hypophosphataemia and hypomagnesaemia. This condition is termed refeeding syndrome. The circulating volume increases due to the hyperinsulinaemia which occurs during the feeding phase. Furthermore a shortage of ATP occurs and the heart may fail. In efforts to establish feeding, a weight increase of not more than 1 kg per week should be attempted; if the weight increases by more than this, then fluid retention is the probable cause.

Vasculitis due to gemcitabine.

We report the first occurrence of gemcitabine-induced vasculitis. It concerns a 45-year-old man diagnosed with non-small lung cancer since 2 months. After the first cycle of chemotherapy, consisting of gemcitabine and cisplatin, he developed myalgia and swelling of arms and legs with impairment of movement. This re-occurred during the second cycle of chemotherapy. Further anemia, elevated ESR and increased creatininephosphokinase. A surgical biopsy showed leucocytoclastic vasculitis and necrosis of muscle tissue. The chemotherapy was stopped and the complaints disappeared and did not return.

[Diagnostic image (71). A woman with obesity, diabetes mellitus and use of corticosteroids. Mediastinal lipomatosis]. / Diagnose in beeld (71). Een vrouw met adipositas, diabetes mellitus en corticosteroïdgebruik. Mediastinale lipomatose.

In a 69-year-old obese woman on prednisone treatment for temporal arteritis a widened mediastinum on chest X-ray proved to be mediastinal lipomatosis on CT-scan.