Clinical experience of Rotablator

26 patients (27 lesions) who had severe calcified and diffuse lesions underwent Rotablator treatment, lesion characteristics were type B2, Type C of AHA/ACC classification. There were no patients who had type A1, type B1 lesions. Procedural success rate is 96%, coronary perforation occurred in one patient but not necessary for surgical treatment. Non Q myocardial infarction occurred only in one patient. Follow up Angioplasty were performed 1 and 3 months later after procedures. There were no restenosis after 1 month, but after 3 months, 56% of patients had restenosis.     

Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.     

Induction of antitumor immune response by NK-cell-sensitive target cells transfected by B7-1 gene

The aim of the study was to evaluate the safety and efficacy of TVT (tension-free vaginal tape) for the surgical treatment of stress urinary incontinence. The design was a prospective open multicenter study including six centers, each operating an approximately 20 patients. In total 131 patients suffering from genuine stress incontinence were included. They were followed for at least 1 year using a specific protocol for objective and subjective evaluation of the outcome. All patients underwent the operation under local anesthesia. Mean operation time was 28 minutes (range 19-41 minutes); 119 (91%) of the patients were cured according to the protocol and another 9 (7%) were significantly improved. There were 3 (2%) failures. The majority of the patients (about 90%) were operated upon on a day-care basis, which implied that they were released from the hospital within 24 hours, with no postoperative catheterization. No defect healing and no tape rejection occurred. Three patients needed an indwelling catheter for 3 days. In 1 patient catheterization was necessary for more than 10 days. Two uncomplicated hematomas and one uncomplicated bladder perforation occurred. Based on the results, we conclude that TVT is a safe and effective ambulatory procedure for surgical treatment of genuine stress urinary incontinence.     

Serum lipids in patients with liver disease (author''s transl)

A long-term controlled therapeutic trial of gefarnate (600 mg daily) in the treatment of chronic gastric ulcer was carried out in 32 patients. Assessment was based on the clinical course and on repeated radiological and endoscopic examinations, which were performed after 3-months' treatment, at the end of the 1-year trial period, and towards the end of a follow-up period of approximately 2 1/2 to 3 1/2 years. In men with gastric ulcer, gefarnate proved to be highly effective, with 10 out of the 11 patients who received this treatment showing persistent healing of the ulcer compared with only 4 out of the 11 who were on dummy treatment. In the very small group of women it was not possible to show any difference between treatments. No adverse reactions to gefarnate occurred. These results suggest that gefarnate is a safe and effective treatment for chronic gastric ulcer.     

Effect of adenosine analogues on the expression of matrix metalloproteinases and their inhibitors from human dermal fibroblasts

The effect of the cytostatic and antiviral adenosine analogues 3-deazaadenosine (c3Ado) and 3-deaza-(+/-)-aristeromycin (c3Ari) on human skin fibroblasts was studied. Variables examined were cell morphology, viability, DNA fragmentation, expression of matrix metalloproteinases (MMPs) and matrix metalloproteinase inhibitors (TIMPs). None of these variables were changed when cells were exposed to c3Ari concentrations ranging from 10(-5) to 10(-3) M or 10(-5) M c3Ado. However, large changes in cell morphology, viability and expression of MMPs and MMP inhibitors occurred when fibroblasts were treated with 10(-4) or 10(-3) M c3Ado. Cells rounded up, shrank in volume, some detached and viability was lost without any detectable fragmentation of DNA. These changes in morphology and viability were associated with a differentiated expression of MMPs and MMP inhibitors. A large increase in collagenase activity occurred, and depending on the concentration of the adenosine analogue and the length of treatment, this change in activity could be shown to be due to one or a combination of the following factors: an increased synthesis of the collagenase protein, a decreased production of TIMP-1 or an increased activity of the collagenase superactivator, stromelysin. In contrast to this, treatment with c3Ado resulted in a decreased gelatinase activity, which in part could be attributed to an increased production of an inhibitor that seemed to affect gelatinase but not collagenase. The cellular changes induced by c3Ado seemed to reflect some of the alteration in the metabolic machinery that appears during a drug-induced or programmed/controlled death of a dermal cell. The different effects exerted by these two adenosine analogues on dermal fibroblasts can at least in part explain why c3Ado have previously been shown to be more toxic than c3Ari in animal models.     

Transoral metal implant removal after ventral C2/C3 spondylodesis in pharyngo-vertebral fistula

A 26-year-old man sustained a C2 arc fracture. Ventral spondylodesis using an H-plate was performed. The patient developed a pharyngovertebral fistula which remained undetected for 1 year. Spontaneous fusion of C3/C4 and osteolysis of the cortical block occurred. The fistula was demonstrated intraoperatively and the implant was transorally removed. No further problems occurred after this unusual method of treatment. The anatomy of the cervical spine, special problems of intensive care patients and the use of proper instrumentation are discussed.     

Differential effects of N-methyl-D-aspartate receptor blockade on nociceptive somatic and visceral reflexes

OBJECTIVE: A Phase I study was conducted to determine the safety, toxicity, and maximum tolerated dose of preirradiation chemotherapy using carmustine (BCNU) and cisplatin in the treatment of high-grade gliomas. METHODS: Patients with newly diagnosed high-grade gliomas received BCNU and cisplatin after surgery, both before and during definitive radiation therapy. Preirradiation chemotherapy consisted of an administration of 40 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 and repeated at 8 weeks to coincide with the start of radiation therapy. Postradiation chemotherapy consisted of an administration of 200 mg/m2 BCNU once every 8 weeks for four cycles. Radiation therapy consisted of 160-cGy fractions administered twice daily for 15 days, yielding a total dose of 4800 cGy. Dose escalation of BCNU was planned. If hematological toxicity was mild, the dose of cisplatin was to be held constant and BCNU dose escalated to 50 mg/m2 on Days 1 through 3. RESULTS: Eighteen patients were studied. The hematological toxicity was dose-limiting. Grade 3 or 4 leukopenia occurred in each of 10 patients (56%), and Grade 3 or 4 thrombocytopenia occurred in each of 9 patients (50%). Other toxicities included anorexia (94%), nausea (83%), emesis (33%), alopecia (94%), mild ototoxicity (50%), and, in one patient, death as a result of BCNU pulmonary toxicity. The median survival time was 14 months. Objective responses occurred in 45% of the patients evaluable for response. The maximum tolerated dose of this combination was 50 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 before radiation and repeated in 8 weeks to coincide with the start of radiation. CONCLUSION: This schedule of the preirradiation administration of BCNU and cisplatin with accelerated hyper-fractionated radiation therapy for the treatment of high-grade gliomas provides a less toxic alternative to that of previous studies of preirradiation chemotherapy with these agents and merits further investigation.     

Experimental murine IgA nephropathy following passive administration of vomitoxin-induced IgA monoclonal antibodies

Oral exposure of mice to vomitoxin (VT) induces elevated levels of serum IgA, circulating IgA immune complexes (IgA-IC), mesangial IgA deposition and haematuria, which all mimic the clinical signs of human IgA nephropathy (IgAN). To further assess the effects of VT-induced IgA in the murine model, B6C3F1 and BALB/C mice were injected intraperitoneally with affinity-purified monoclonal IgA derived from Peyer's patch hybridomas of VT-exposed mice. In B6C3F1 mice, serum IgA, IgM and IgA-IC levels were increased two- to fivefold in treatment groups after 4 and 6 wk compared with controls, whereas increases in serum IgG as high as 18-fold were observed. Urinary erythrocyte counts were also significantly elevated in treatment groups after 2, 4 and 6 wk compared with controls. Concurrent increases in IgA and IgG complexes containing casein, the dietary protein source, occurred in treatment mice. Mesangial IgA, IgG, IgM and C3 deposition were significantly increased in all treatment mice after 6 wk. Electron-dense deposits occurred in the glomeruli of IgA-injected mice after 6 wk. All the above parameters were similarly affected in BALB/C mice. Injection of IgA-secreting hybridoma cells into BALB/C mice increased serum IgA, IgA-IC and IgG levels as well as elevated mesangial IgA, IgG and C3 deposition and haematuria after 2-3 weeks compared with controls. In total, these data indicate that passive administration of VT-induced IgAs can induce the hallmarks of IgA nephropathy. Casein, an antigen found in the diet used for these mice, appeared to form IC with IgA or IgG and these IC may participate in the pathogenesis of this nephropathy.     

Diuretic response to cyclophosphamide in rats bearing a matrix metalloproteinase-9-producing tumour

When cyclophosphamide (CY) (100-120 mg kg(-1)) was administered intravenously (i.v.) to normal F-344 rats, oliguria occurred over the 5-day observation period. Conversely, in rats bearing matrix metalloproteinase-9 (MMP-9) producing 13762NF mammary adenocarcinoma (MTLn3 clone), polyuria occurred chiefly during the first 24 h after CY treatment. In parallel with urine volume, a decrease in the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was observed during the first 5 days after CY treatment in normal rats, but it increased in MTLn3-bearing rats. No elevation in blood urea nitrogen (BUN) or serum creatinine (Cr) values was observed for either group. Both urine volume and urinary excretion of NAG after CY treatment were lower in rats bearing the MTC clone (lower production of MMP-9) than for those bearing the MTLn3 clone. In the case of treatment with cisplatin (CDDP, 4-6 mg kg(-1)), urine volume, urinary NAG excretion and BUN and serum Cr values all increased in normal rats and were all found to be higher in MTLn3-bearing rats than in normal rats. The diuretic response to these drugs in tumour-bearing (TB) rats may be associated with MMP-9 produced by the tumour cells. This report suggests that the nephrotoxicity due to anti-cancer drugs may change when the drugs are used for the treatment of patients bearing a MMP-9-producing tumour.     

Effects of psychotherapeutic strategies in the treatment of suicide attempters.

In an investigation of the effectiveness of strategies in the treatment of suicide attempters, 15 psychiatric inpatients admitted for suicide attempts without a diagnosis of psychosis, alcoholism, or drug abuse were assessed pre- and posttreatment for suicidal ideation, hopelessness, means–end problem solving, and flexibility of thinking. Ss were randomly assigned to a cognitive-restructuring, problem-solving, or nondirective control group for treatment. Ss recorded instances of suicidal thoughts on a daily basis and participated in 10 1-hr individual therapy sessions. Results show that changes in hopelessness and suicidal intention occurred for all 3 treatment conditions, which succeeded in reducing Ss' suicidal intentions. At posttreatment, only the problem-solving and nondirective groups were significantly different from each other on measures of hopelessness. (32 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Minimally displaced distal radius fractures: do they need plaster treatment?

In a prospective, randomized trial, minimally displaced distal radius fractures were divided into two groups: those treated with plaster immobilization for 1 week compared with 3 weeks. Functional Cooney scores were determined at 6 weeks, 3 months, 6 months, and 1 year. No statistical differences could be found in functional outcome between the groups at any time during the evaluation. Although patients did not allow immediate functional treatment in the presence of a fracture, we could not find any differences between 1 week or 3 weeks of plaster treatment. No further dislocation occurred, and all patients experienced eventful healing with good and excellent results in 92% of the cases. We believe, therefore, that only minimal immobilization is required in these fractures and that they should be mobilized as soon as comfort allows.     

The role of lipogenesis in the development of obesity and diabetes in Israeli sand rats (Psammomys obesus)

In order to optimize the therapeutic index of combining etoposide, epirubicin, cisplatin, 5-fluorouracil (5-FU), leucovorin (EEPFL) chemotherapy in the treatment of advanced gastric cancer, a trial of a novel schedule of weekly administration was conducted. Weekly EEPFL treatment consisted of a concomitant boost of etoposide 40 mg m(-2) i.v. over 30 min, epirubicin 10 mg m(-2) i.v. over 5 min to a backbone regimen, weekly PFL chemotherapy with cisplatin 25 mg m(-2), 5-FU 2200 mg m(-2), leucovorin 120 mg m(-2) given simultaneously by 24-h i.v. infusion. Response, survival and toxicity were evaluated. Forty-two patients were studied. Median age was 69 (range 31-84) years. Twenty-six per cent of patients showed complete response and 45% partial response. The overall response rate was 71% (95% confidence interval 58-84%). For a total of 507 weekly EEPFL cycles delivered, the incidence of grade 4 leucopenia was 1% of cycles. One patient died of neutropenia septicaemia. There was no other grade 4 toxicity. Grade 3 and 2 leucopenia occurred in 7% and 14% of cycles. The incidence of grade 3 and 2 mucositis was 1% and 3% of cycles. Grade 3 and 2 diarrhoea occurred in 0.4% and 1.6% of cycles. Overall median survival was 10 months (range 3-41+ months). Weekly EEPFL chemotherapy is an effective regimen with tolerable toxicities in the treatment of advanced gastric cancer. A randomized controlled clinical trial to formally assess the efficacy and benefit of EEPFL chemotherapy is under way.     

Accelerated-interrupted radiation therapy given concurrently with chemotherapy for locally advanced non-small cell lung cancer

PURPOSE: To evaluate the efficacy of multidrug chemotherapy combined with accelerated radiation therapy in the treatment of localized but unresectable non-small cell lung cancer. PATIENTS AND METHODS: Between September 1990 and February 1993, 35 patients with Stage III (15 IIIA & 20 IIIB) non-small cell lung cancer were entered on a protocol using combined accelerated radiation therapy and chemotherapy. Radiation therapy consisted of 55.6 Gy in 30 fractions (1.8 Gy bid for 5 consecutive days given in 3 weeks [total of 15 days], every other week). Chemotherapy consisted of cisplatin (10 mg/m2), vinblastine (4 mg/m2), 6-thioguanine (40 mg bid), and 5-fluorouracil (400 mg/m2 as continuous infusion) given concomitantly with radiation therapy. Approximately 3 weeks following completion of radiation therapy, two cycles of consolidation chemotherapy were given, consisting of two doses of cisplatin (120 mg/m2) 4 weeks apart and six doses of vinblastine (4 mg/m2) given on two consecutive days every other week for 3 weeks. RESULTS: Six patients were still alive at last follow-up; for them the median follow-up time is 47 months (range, 39-55.8). The median survival time is 17.5 months. The 1-, 2-, 3- and 4.5-year survival rates are 69%, 37%, 20% and 17%, respectively. Overall response rate is 63%, with 51.5% partial response and 11.5% complete response rates. Esophagitis occurred as follows: Grade 4 = 0, Grade 3 = 1, Grade 2 = 6, and Grade 1 = 13. No patient developed Grade 3 or 4 acute respiratory toxicity. Significant hematologic toxicity occurred as follows: 37% Grade 3 and 31% Grade 4 leukopenia. Radiation pneumonitis occurred in two patients. DISCUSSION: The regimen tested in this protocol appears to be very well tolerated with minimal pulmonary or esophageal toxicity. This, coupled with the shortened course of radiation therapy and the ability to deliver the combined radiation and chemotherapy portion of the treatment on an outpatient basis most of the time, has made multi-modality treatment for this malignancy much easier and more convenient for patients. In addition, the favorable survival in this group of patients with locally advanced disease is very encouraging and warrants further study.     

Effect of chronic treatment with typical and atypical neuroleptics on the expression of dopamine D2 and D3 receptors in rat brain

The effect of chronic treatment (21 days) with typical and atypical neuroleptics on the expression of striatal and limbic D2 and D3 dopamine receptors was investigated in rat brain by in situ hybridization and receptor autoradiography. Haloperidol and sulpiride increased D2 receptor expression in striatal and limbic areas. In contrast, clozapine had no effect on D2 receptor expression. Haloperidol decreased D3 receptor expression in limbic areas, with the exception of the islands of Calleja where an increase occurred. Sulpiride and clozapine increased D3 receptor expression in limbic and striatal regions but decreased D3 receptor expression in the islands of Calleja. This study demonstrates that chronic treatment with typical and atypical neuroleptics produces different regionally specific changes in limbic and striatal D2 and D3 receptor expression. The alterations in dopamine receptor expression were different for each drug, but a distinction between the effects of atypical and typical neuroleptics could be made. Comparison of mRNA levels in animals which were not withdrawn from drug treatment with those that were withdrawn, demonstrated that some changes in receptor expression occurred during drug treatment, whilst others only manifested when drug treatment had ceased. The different regulation of dopamine D2 and D3 receptor expression by typical and atypical neuroleptics may have relevance to the ability of these drugs to cause extrapyramidal side-effects.     

Mycotic aneurysm of the extracranial carotid artery: an uncommon complication of bacterial endocarditis

This report describes a case involving mycotic aneurysm of the extracranial internal carotid artery occurring as a complication of staphylococcal endocarditis in a patient with systemic lupus erythematosus. Three main points are emphasized: (1) this complication occurred in an immunodepressed patient; (2) surgical treatment consisted of aneurysmorraphy using absorbable suture; (3) the outcome was successful with a follow-up of 24 months.     

Effects of combretastatin on murine tumours monitored by 31P MRS, 1H MRS and 1H MRI

PURPOSE: Combretastatins have tubulin-binding activity and are being investigated for their toxicity against tumour vasculature. We report the use of 31P and 'H magnetic resonance (MR) spectroscopy and 1H MR imaging for monitoring the effects of combretastatin A-4 prodrug (100mg/kg, i.p.) on energy metabolism and necrosis, respectively, in the C3H murine mammary tumour. MATERIALS AND METHODS: The tumours (volume ca. 200mm3) were grown in the hind foot of mice. MR examinations were performed without anaesthesia within a 7.1 Tesla magnet. 31P MRS (TR = 6 s) was performed before treatment and at 1-, 2-, 3-, and 24-h after injection of drug or saline via an i.p. line. 1H MRS (PRESS; 24microl voxel; TR = 2 s; TE = 135 ms) and both T1-weighted (TR = 0.2 s; TE = 0.02 s) and T2-weighted (TR = 2 s; TE = 0.20 s) 1H MRI were performed before treatment and 2.5 and 24 h afterwards. RESULTS: The ratio beta-nucleotide triphosphate/inorganic phosphate fell by 33% within 1 h of treatment and remained constant for a further 2 h. A small but significant fall in pH (by 0.11 units) was observed at 1 h. Although an increase in the 1H MR spectroscopy signal at about 1.32 ppm (predominantly from lactate) was observed in some tumours following combretastatin treatment, this effect was not seen consistently. No changes in the intensity of T2-weighted 1H MR images or in tumour necrosis (measured histologically) were detected within 3 h of treatment. CONCLUSIONS: The reduction in tumour energetics and pH was consistent with a reduction in tumour blood flow but this occurred before any significant incidence of haemorrhagic necrosis was detected. The combretastatin dose used to achieve these effects was less than one tenth of the maximum tolerated dose in mice.     

Pseudomonas aeruginosa endocarditis. A report of nine cases

9 cases of Pseudomonas aeruginosa endocarditis are reported and the results of this study are compared with the data of the literature. The source of infection was known in 8 patients: 7 were nosocomial infections (cardiac catheterization in 5 cases, cardiac surgery in 2 cases). The diagnosis was made in 8 patients with left-sided endocarditis. In 1 patient tricuspid endocarditis was diagnosed on postmortem examination. Carbenicillin associated with an aminoglycoside antibiotic appeared to be the most effective treatment when prescribed for several weeks. 6 of 9 patients died of uncontrolled septicemia, 3 of whom underwent surgery which was twice performed because of poor hemodynamic status. In the other 3 patients drug administration was effective at first. However, a relapse occurred in these three cases compelling another effective antibiotic therapy. Surgery was peformed in these three patients. Valve cultures were negative in two cases and positive in 1. These 3 patients survived. They are still alive after a follow-up period of 2 or 3 years.     

Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage

Cabergoline (CAB), a long-lasting dopamine-agonist, specific for the D2 receptor, is effective in normalizing serum PRL levels in most patients with microprolactinoma or idiopathic hyperprolactinemia. Because few data are presently available on the effects of CAB treatment in macroprolactinomas, the aim of this open-label study was to investigate whether this drug was effective in producing tumor shrinkage, as well as in normalizing PRL levels. Twenty-three patients with macroprolactinoma entered this study 15 patients had had no treatment, whereas the remaining 8 patients had been previously treated with bromocriptine, which was with-drawn because of intolerance. Three of 23 patients had undergone unsuccessful surgery. Pretreatment serum PRL levels ranged from 100-3860 micrograms/L. CAB was administered at a dose of 0.5-3 mg once or twice a week for 12-24 months. Magnetic resonance imaging (MRI) scans were performed before and 3, 6, 12, and 24 months after the beginning of treatment, to evaluate tumor shrinkage, defined as a decrease of at least 80% of baseline tumor volume. After 3-6 months of treatment with a low dose (0.5-1 mg/week), serum PRL levels normalized in 18 patients. In the remaining 5 patients, whose serum PRL levels were not normalized, the dose was increased to 2-3 mg/week. This schedule caused the normalization of PRL levels in 1 patient, whereas in the remaining 4 patients, PRL levels were reduced to 30-82 micrograms/L. A tumor volume reduction greater than 80% at MRI occurred in 14 of 23 patients (61%) after CAB treatment (from 2609.4 +/- 534.7 to 530.1 +/- 141.3 mm3 at the 12-24th month follow-up, P < 0.001). A volume reduction of 41.8 +/- 3.4% was already evident after 3 months (1436 +/- 285.9 mm3; P < 0.001). The complete disappearance of the tumor mass at MRI occurred after 6 months of treatment with CAB in 1 patient, and in 5 patients after 1 yr of treatment. An improvement of visual field defects was obtained in 9 of the 10 patients presenting visual impairment before CAB treatment. The drug was tolerated well by all patients. Only 1 patient experienced mild nausea, which disappeared spontaneously after the 2nd day of treatment. Long-term, a low dose of the D2 receptor agonist CAB significantly reduced tumor volume and normalized serum PRL levels in a great majority of patients bearing macroprolactinoma. This treatment met with excellent patient compliance. This study suggests that CAB can be used as a first choice drug treatment in macroprolactinomas, as already shown for microprolactinomas and idiopathic hyperprolactinemia.     

Regulation of ion channel expression by cytoplasmic subunits

The present phase II trial was undertaken to assess the efficacy and toxicity of a combination of paclitaxel and carboplatin as first-line chemotherapy in patients with metastatic transitional cell carcinoma of the urothelium. Twenty patients (age range 50-79 years; inclusion criteria: WHO performance status 0-2, no previous cytotoxic treatment) with metastatic transitional cell carcinoma of the urothelium were recruited and received cytotoxic treatment with paclitaxel at a dosage of 175 mg m(-2) administered over a 3-h infusion and carboplatin given at an AUC of 5 mg ml(-1) min (according to creatinine clearance) administered every 21 days. A total of 65% of patients achieved remissions (CR+PR), with CR occurring in 40% of patients. A further 15% of patients experienced stable disease. Remissions occurred after 2.4 +/- 0.8 (mean +/- standard deviation; range two to four) treatment cycles. The mean duration of responses (CR+PR) was 8.5 +/- 5.5 months. After a mean observation period of 11.4 +/- 4.8 months, 16 patients (80%) are alive. Toxicity included alopecia of WHO grade 3 in all patients, leucopenia of WHO grades 1 and 2 in ten patients, grade 3 in eight and grade 4 in two patients and, finally, severe thrombocytopenia grade 3 in only three patients. Non-haematological toxicity consisted of polyneuropathy of WHO grade 1 in 13 patients and grade 2 in five patients. We thus conclude that a combination of paclitaxel and carboplatin at the given dosage and schedule constitutes an active, well-tolerated first-line cytotoxic treatment for patients with metastatic urothelial cancer.     

Enhanced acute toxicity in oropharynx carcinoma treated with radiotherapy and concomitant cisplatin, 5-fluorouracil and mitomycin C

The aim of this study was to establish the feasibility of giving concomitant radiotherapy and 3 cycles of chemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced inoperable oropharyngeal cancer. From March 1990 to September 1993, 27 male patients (mean age 55 years) were included in this study. 3 patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). All patients received conventional radiotherapy delivering 70 Gy in 35 fractions and 52 days, and three cycles of chemotherapy starting on day 1, 21 and 42 with CDDP 20 mg/m2 and 5-FU 400 mg/m2 day 1 to day 4, and MMC 10 mg/m2 day 1. With a mean follow-up of 34 months (17-59), 10 patients (37%) were alive and free of disease. Among the 17 other patients, 8 died of cancer. Crude locoregional control rate was 78%, and probability of local control at 1 and 2 years was 85 and 80%, respectively. One- and 2-year survival rates were 48 and 31%, respectively, for both overall and disease-free survival. Grade 3 or 4 mucositis occurred in 22 patients (81%); enteral feeding was necessary for 63%; mean weight loss was 5.7 kg. Grade > 2 thrombocytopenia occurred in 11 patients (41%), grade > 2 neutropenia in 8 patients (29%), grade > 2 anaemia in 4 patients (15%). Febrile neutropenia or aplasia occurred in 5 patients (19%). 2 patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 1 month after treatment with grade 4 thrombocytopenia and septicaemia. In conclusion, a high complete response rate has been achieved with this concomitant chemo- and radiotherapy, but with severe digestive and haematological toxicity. Addition of MMC to 5-FU and CDDP might have been responsible for this increased toxicity. This therapeutic combination is therefore not routinely feasible.