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Notes: A 43-year-old woman was admitted to hospital with a history of recurrent attacks of vertigo, which had been treated with carbamazepine for 4 weeks. The patient presented with fever, cold chills, lymphadenopathy, and erythematous and highly infiltrated skin. The Nikolski phenomenon was negative and there was no pruritus. Symptoms had begun 5 days earlier, with a diffuse maculopapular exanthema, first localized on the breast and trunk, with consecutive generalization, and accompanied by a severe enteritis. The exanthema worsened to a state of generalized erythroderma (〈link href="#f1"〉Fig. 1).〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1832:IJD_1832_f1"/〉The patient's left arm and right hand showing infiltrated, edematous, and erythematous skin with a hemorrhagic aspectThe patient's performance status was 2, according to the World Health Organization (WHO). Laboratory findings showed a white blood cell count of 22.4 × 109/L [normal, (4.0–10.0) × 109/L] with 32% eosinophils (normal, up to 4% of total circulating leukocytes), an aspartate aminotransferase (ASAT) level of 63 U/L (normal, 0–15 U/L), an alanine aminotransferase (ALAT) level of 95 U/L (normal, 0–19 U/L), a γ-glutamyl transpeptidase (γ-GT) level of 176 U/L (normal, 4–18 U/L), and an alkaline phosphatase (AP) level of 305 U/L (normal, 60–170 U/L). The C-reactive protein (CRP) level was 8.9 mg/dL (normal, 〈 1 mg/dL). Renal function, chest radiography, and abdominal sonography were completely normal. Serologic tests for viral infections, including cytomegalovirus, Epstein–Barr virus, parvovirus, Coxsackievirus, human immunodeficiency virus, and hepatitis A, B, and C virus, were negative. Stool cultures and serology were negative for bacteria, protozoa, or helminthic eggs. Blood cultures and nasal–throat swabs were repeatedly negative. Carbamazepine was discontinued from day 1 of hospitalization. From day 1–5 of admission, the patient received intravenous therapy with 1000 mg/day prednisolone- 21-hydrogensuccinate-sodium and diphenhydramine (60 mg twice daily), and antimicrobial therapy with clindamycin (900 mg three times daily) and fosfomycin (8000 mg twice daily), a therapy with good efficacy against Gram-positive cocci (Bergan T. Pharmacokinetic comparison between fosfomycin and other phosphonic acid derivatives. Chemotherapy 1990; 36 (Suppl. 1): 10–18), was given for a total of 7 days. Fever persisted, however, and the physical status deteriorated within the first 3 days of hospitalization. The creatine kinase (CK) level increased to 108 U/L (normal, 0–70 U/L), with a CK-muscle-brain (MB) fraction of 33.6% (normal, 0–6%). The patient was monitored. Electrocardiography (ECG) showed tachycardia with frequent ventricular extrasystoles and tachypnea, but regular blood pressure and adequate oxygen saturation.After 1 week of hospitalization, the patient's status improved, the number of eosinophils was reduced to 6%, and an acute onset of rheumatic disease was ruled out by negative blood samples for antinuclear antibodies, antineutrophil cytoplasmic antibodies, and complement system. After two more weeks in hospital, the cardiac symptoms had resolved, most laboratory parameters had returned to normal values, and the skin had markedly improved. The patient was discharged with local therapy consisting of 30% betamethasone cream.Seven days later, the patient was re-admitted. She presented with a new, bright red urticarial exanthema over the entire body with pruritus. She had a return of fever, up to 38.2 °C, and a white blood cell count of 2.4 × 109/L with 11% eosinophils; CRP was 2.38 mg/dL, γ-GT was elevated at 106 U/L, but liver transaminases, CK, and CK-MB fraction were normal. Fever was recurrent, with spikes up to 37.8 °C.The diagnosis of a recurrent carbamazepine-induced DRESS (drug rash with eosinophilia and systemic symptoms) syndrome was made, and further therapy with a low-dose oral glucocorticosteroid was considered. The patient refused further medication, and therefore a watch and wait strategy was planned. Again, 7 days after re-admission, the skin returned to normal and the patient was discharged. At an outpatient visit after 1 week, the patient noted a modest recurrent temperature increase of 37.8 °C, which she treated with nonsteroidal antiphlogistics, but the skin and laboratory values were completely normal.Two weeks later, i.e. 6 weeks after the acute onset of DRESS syndrome, she again showed new, sharply limited, livid-reddish macular skin lesions with central scaling and hyperkeratotic areas, localized on the ventral trunk, the legs, and the soles. The new skin lesion was treated with topical ointment consisting of 3% salicylate, 10% urea, and propyleneglycol in a neutral base. At the control visit, 2 weeks later, the lesions had markedly improved. The neurologic medication for vertigo had been changed to lamotrigine 3 weeks before, which was well tolerated. Follow-up visits were conducted at 3-week intervals for two more months, but the skin symptoms and fever did not recur. Taken together, complete resolution of all symptoms was achieved 9 weeks after the discontinuation of treatment with carbamazepine.

Notes: Abstract A pregnant 33-year old woman developed nystagmus and cerebellar ataxia. A tumor in the roof of the fourth ventricle was diagnosed. The tumor was subtotally removed using microneurosurgical techniques. The histopathological diagnosis was choroid plexus papilloma (CPP). Twenty-one months later, the tumor recurred and was reoperated. Histologically the tumor displayed now increased mitotic activity and pleomorphism. Radiation therapy of the neuroaxis was performed. Within 59 months, the CPP recurred 3 more times with neuroradiological evidence of extensive spinal seeding. After several palliative irradiations, including 2 gamma-knife boosts, the patient was referred to chemotherapy. She was treated with CCNU (Lomustin) 100 mg/m2 orally (12 cycles, cumulative dosis 1440 mg/m2). Within 42 months, there was no new local recurrence and spinal seeding showed significant regression. Clinically the patient improved and stabilized, but needs continuous support because of persisting severe gait ataxia. The course of disease in our patient provides evidence for therapeutic efficacy of CCNU in recurrent CPP.

Notes: Abstract Purpose. A phase II trial was performed to investigate the efficacy and tolerance of gemcitabine, vinorelbine, and recombinant human granulocyte colony‐stimulating factor (G‐CSF) in advanced breast cancer. Patients and methods. Between April 96 and August 97, 60 patients entered this trial. Forty‐five patients were previously untreated and 15 patients had failed previous palliative chemotherapy with (n = 10) or without anthracyclines (n = 5). Therapy consisted of gemcitabine 1000 mg/m2 on days 1 + 15 + 21 and vinorelbine 40 mg/m2 on days 1 + 21, both diluted in 250 ml saline and infused over 30 min. G‐CSF was administered at 5 μg/kg/day subcutaneously from days 2–6 and 22–26. Courses were repeated every 5 weeks. Treatment was continued in case of response or stable disease until a total of six courses. Results. The overall response rate was 55.5% for patients who had not received prior palliative chemotherapy (95% confidence interval, 40%–70.3%), including 5 CR (11.1%) and 20 PR (44.4%) 12 patients (27%) had stable disease (SD), and 8 (18%) progressed. Second‐line treatment with this regimen resulted in 6/15 (40%) objective remissions, 5 had SD, and 4 PD. The median time to progression was 9.5 months (range, 1.5–28) in previously untreated patients, and 7.0 months (range, 2–23) in those who had failed prior chemotherapy. After a median follow‐up time of 15 months, 44 patients (73%) are still alive with metastatic disease. Myelosuppression was commonly observed, though WHO 3 and 4 neutropenia occured in only 9 (l5%) and 2 patients (3%), and was never complicated by septicaemia; grade 3 anemia was noted in 2 patients. Severe (WHO grade 3) nonhematologic toxicity was rarely observed, and included nausea/emesis in 3 and constipation in 2 patients. Conclusions. Our data suggest that gemcitabine and vinorelbine plus G‐CSF is an effective and tolerable first‐ as well as second‐line combination regimen for treatment of advanced breast cancer.

Notes: Abstract Purpose.A phase II study was performed to investigate the efficacy and tolerance of alternating docetaxel and epirubicin/cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with advanced breast cancer who failed previous non-anthracycline/taxane-containing palliative chemotherapy. Patients and methods.Between November 96 and June 98, a total of 45 patients participated in this trial. Chemotherapy consisted of docetaxel 100 mg/m2 given as a 1-h infusion on day 1, and epirubicin 100 mg/m2 plus cyclophosphamide 800 mg/m2 both adminstered on day 21. G-CSF 5 μg/kg/day was given subcutaneously from days 22–28 during each cycle. Treatment courses were repeated every 42 days for a total of three courses unless prior evidence of progressive disease. Results.The overall response rate was 57.8% (95% confidence interval, 42.1–72.3%), including seven complete (15.5%) and 19 partial remissions (42.3%); nine patients (20%) had stabilization of disease and 10 (22.3%) progressed. The median time to treatment failure was 7.0 months (range 1.5–26.0), and the median overall survival time 15.0 months (range 2.0–37.0+) with 12 patients (27%) currently still alive with metastatic disease. Myelosuppression was commonly observed with WHO grade 3/4 neutropenia in 20 patients (44%) complicated by septicemia in five (11%). Severe nonhematologic toxicity included stomatitis in five patients (11%), skin and peripheral neurotoxicity each in one patient; alopecia was seen in all 45 patients with complete hair loss in 26 (58%). Conclusions.Our data suggest that alternating docetaxel and epirubicin/cyclo-phosphamide plus G-CSF is an effective and tolerable second-line combination regimen for the treatment of advanced breast cancer.