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PubMed1998

Dose-dependent reduction of cerebral blood flow during rapid-rate transcranial magnetic stimulation of the human sensorimotor cortex.

Rapid-rate transcranial magnetic stimulation (rTMS) was used to stimulate the primary sensorimotor cortex in six healthy volunteers while regional changes in cerebral blood flow (CBF) were simultaneously measured by means of positron emission tomography. A figure-eight TMS coil (Cadwell Corticoil) was positioned, using frameless stereotaxy, over the probabilistic location of the left primary sensorimotor cortex, and a series of brief 10-Hz trains of TMS was delivered at subthreshold intensity during each of six 60-s scans. The scans differed in the number of trains delivered, namely 5, 10, 15, 20, 25, and 30 trains/scan, respectively. In the left primary sensorimotor cortex, CBF covaried significantly and negatively with the number of stimulus trains. These CBF decreases may reflect TMS-induced activation of local inhibitory mechanisms known to play a role in TMS-related phenomena, such as the electromyographic silent period.

Adult↗
PubMed2004

High-dose mycophenolate mofetil in the treatment of posttransplant glomerular disease in the allograft: a case series.

BACKGROUND: Glomerular disease is an important cause of allograft loss. Treatment regimens for posttransplant glomerular disease are not well defined. Several reports have demonstrated that mycophenolate mofetil (MMF) is effective in treating native kidney glomerular disease. The effects of MMF are dose related. Therefore, we hypothesized that high-dose MMF (3 g/day) would be effective in treating glomerular disease in the allograft, minimizing the need for intravenous steroids and/or cyclophosphamide. This case series describes the results of the use of high-dose MMF in 6 patients. METHODS: High-dose MMF (3 g/day) was used to treat biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, proliferative lupus nephritis, and perinuclear antineutrophil cytoplasmic antibodies glomerulonephritis) in 6 renal transplant recipients. Patients were offered this treatment if they had failed or did not tolerate standard treatment regimens. Remission was defined by a decrease or stabilization of serum creatinine, decrease in proteinuria and, where applicable, improvement in immunological markers of disease. RESULTS: All 6 patients had disease remission after starting MMF with the most common side effect being leukopenia, which responded to dose reduction. CONCLUSIONS: High-dose MMF may be an effective agent in treating glomerular disease in the allograft.

Adult↗
PubMed2006

Reduced incidence of severe palmar-plantar erythrodysesthesia and mucositis in a prospective multicenter phase II trial with pegylated liposomal doxorubicin at 40 mg/m2 every 4 weeks in previously treated patients with metastatic breast cancer.

PURPOSE: The aim of this study was to assess whether the reduction in the total dose of pegylated liposomal doxorubicin (PLD) per cycle from 50 mg/m(2) every 4 weeks to 40 mg/m(2) every 4 weeks can effectively lower the incidence of treatment-related palmar-plantar erythrodysesthesia (PPE) and mucositis. METHODS: Patients received PLD 40 mg/m(2) every 4 weeks, and were evaluated for toxicity prior to each treatment and for response every 8 weeks. RESULTS: All patients were previously treated with at least one chemotherapy regimen for metastatic disease, and 72% of the patients had a prior exposure to an anthracycline. Forty-six evaluable patients received a median of four PLD cycles, with a median dose intensity of 10 mg/m(2)/week and a median cumulative dose of 160 mg/m(2). No National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 PPE was observed in these patients. NCI-CTC grade 3 or 4 mucositis occurred in 4.3% of patients, only. Response rates and survival results observed here were comparable to those observed with PLD 50 mg/m(2) every 4 weeks in a matched patient population. However, patients treated with PLD 40 mg/m(2) every 4 weeks experienced less PPE and mucositis and required clearly less dose reductions and treatment delays. CONCLUSION: The favorable safety profile observed in this study leads us to recommend the use of PLD 40 mg/m(2) every 4 weeks for patients with advanced breast cancer.

Adult↗
PubMed1995

Can cytotoxic dose-intensity be increased by using granulocyte colony-stimulating factor? A randomized controlled trial of lenograstim in small-cell lung cancer.

PURPOSE: The use of granulocyte colony-stimulating factor (G-CSF) to increase cytotoxic dose-intensity was assessed in a randomized trial in better-prognosis small-cell lung cancer (SCLC). Both control and G-CSF arms were subject to the same dose-intensification strategy. PATIENTS AND METHODS: Patients with newly diagnosed SCLC and either no or one adverse prognostic factor were randomized to receive vincristine, ifosfamide, carboplatin, and etoposide (VICE) alone or with recombinant human (rHu)G-CSF (lenograstim) 5 micrograms/kg/d between cycles. Six chemotherapy cycles were given, with prophylactic cranial irradiation after cycle 1 and thoracic irradiation after cycle 3. There was no fixed dose interval. In both arms, patients were eligible for re-treatment when the WBC count was > or = 3 x 10(9)/L and platelet count was > or = 100 x 10(9)/L. No dose reductions were permitted. Dose-intensity was expressed relative to standard every-4-weeks VICE. RESULTS: Sixty-five consecutive patients in one institution were randomized to control (n = 31) or G-CSF (n = 34). WBC and neutrophil counts were consistently higher in G-CSF patients than in the control group, but there were no significant differences in the incidence of febrile neutropenia, antibiotic or transfusion requirements, or days in hospital. In both treatment arms, the median dose-intensity was greater than one for each cycle (control group, P = .0009; G-CSF group, P = .0001). The G-CSF group received a significantly higher dose-intensity than the control group, with the greatest difference in the first three cycles (1.34 v 1.17, P = .001). There were more chemotherapy-related deaths in the G-CSF group than in the control group (six v one), but this group had a better 2-year survival rate (32% with G-CSF, 95% confidence interval [CI], 16 to 48; 15% with controls, 95% CI, 2 to 27). CONCLUSION: The dose-intensity of VICE chemotherapy was increased in both groups. Patients randomized to receive G-CSF achieved a significantly higher dose-intensity than controls. Despite early toxicity, they had a better 2-year survival rate.

Adolescent↗
PubMed1997

Comparative study of dose escalation versus interval reduction to obtain dose-intensification of epirubicin and cyclophosphamide with granulocyte colony-stimulating factor in advanced breast cancer.

PURPOSE: A potential application of hematopoietic growth factors is to obtain an increased dose-intensity. This can be achieved by either higher doses of chemotherapy with standard intervals, or by standard doses with shorter intervals. The potential of these approaches has not been investigated systematically. PATIENTS AND METHODS: In a randomized, multicenter study, 49 advanced breast cancer patients were treated with granulocyte colony-stimulating factor (G-CSF) and either increasing doses of epirubicin and cyclophosphamide with fixed intervals (arm one) or progressively shorter intervals with fixed doses of epirubicin and cyclophosphamide (arm two). A cohort of at least six patients was studied at each interval/dose. A more intensified interval/dose was given if less than 50% of patients encountered a dose-intensity limiting criterium (DILC) in the first three courses. RESULTS: In arm one, epirubicin 140 mg/m2 and cyclophosphamide 800 mg/m2 every 21 days was too toxic. Subsequently, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 was tested with two of 10 patients encountering a DILC. All initial DILCs consisted of febrile neutropenia. In arm two, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely with 14- and 12-day intervals. In the 10-day interval, eight of 12 patients completed the first three cycles without a DILC. In the 8-day interval, seven of eight patients encountered a DILC. Incomplete neutrophil recovery, and to a lesser extent stomatitis, were dose-limiting. CONCLUSION: In combination with G-CSF, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 every 21 days was feasible (projected dose-intensity, 40 mg/m2/wk and 233 mg/m2/wk, respectively). Epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely every 10 days, allowing a projected dose-intensity of 52.5 mg/m2/wk and 350 mg/m2/wk, respectively.

Adult↗
PubMed1993

Selection of anti-scatter grids for different imaging tasks: the advantage of low atomic number cover and interspace materials.

A Monte Carlo computer program has been developed for the study of anti-scatter grids used in diagnostic radiology. The program estimates the scatter from soft tissue phantoms representative of either adult or paediatric examinations and uses dose increase, signal-to-noise ratio improvement and contrast improvement factors to study grid performance. It has been used to quantify the advantage of replacing grids with aluminium covers and interspaces by grids using materials of low atomic number for these components. Two approaches are used. First, the aluminium and low atomic number alternatives are compared for five grid ratios at fixed strip density and width and for tube potentials of 50, 70, 100 and 150 kV. Second, 44 commercially available grids are compared for three different imaging situations (lumbar spine, chest and paediatric). The results demonstrate that grids made with carbon fibre cover and cotton fibre interspace result in greater improvements in contrast and signal-to-noise ratio, and lower dose increase factors, than do grids made with aluminium. The dose reduction varies with irradiation conditions and is generally larger at lower tube potentials, higher grid ratios and lower strip densities. A typical reduction in mean absorbed dose in the patient is 30% in an adult lumbar spine (AP view) at 70 kV with a grid with 36 strips per centimetre and ratio 12.

Adult↗
PubMed2003

Neurotoxic complications of chemotherapy in patients with cancer: clinical signs and optimal management.

Neurotoxic side effects of chemotherapy occur frequently and are often a reason to limit the dose of chemotherapy. Since bone marrow toxicity, as the major limiting factor in most chemotherapeutic regimens, can be overcome with growth factors or bone marrow transplantation, the use of higher doses of chemotherapy is possible, which increases the risk of neurotoxicity. Chemotherapy may cause both peripheral neurotoxicity, consisting mainly of a peripheral neuropathy, and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even coma. In this article we describe the neurological adverse effects of the most commonly used chemotherapeutic agents. The vinca-alkaloids, cisplatin and the taxanes are amongst the most important drugs inducing peripheral neurotoxicity. These drugs are widely used for various malignancies such as ovarian and breast cancer, and haematological cancers. Chemotherapy-induced neuropathy is clearly related to cumulative dose or dose-intensities. Patients who already have neuropathic symptoms due to diabetes mellitus, hereditary neuropathies or earlier treatment with neurotoxic chemotherapy are thought to be more vulnerable for the development of chemotherapy-induced peripheral neuropathy. Methotrexate, cytarabine (cytosine arabinoside) and ifosfamide are primarily known for their central neurotoxic side effects. Central neurotoxicity ranges from acute toxicity such as aseptic meningitis, to delayed toxicities comprising cognitive deficits, hemiparesis, aphasia and progressive dementia. Risk factors are high doses, frequent administration and radiotherapy preceding methotrexate chemotherapy, which appears to be more neurotoxic than methotrexate as single modality. Data on management and neuroprotective agents are discussed. Management mainly consists of cumulative dose-reduction or lower dose-intensities, especially in patients who are at higher risk to develop neurotoxic side effects. None of the neuroprotective agents described in this article can be recommended for standard use in daily practise at this moment, and further studies are needed to confirm some of the beneficial effects described.

Antineoplastic Agents↗
PubMed1989

Combination chemotherapy with vinblastine, ifosfamide and cisplatin in bulky seminoma.

Since 1982, 24 patients with bulky seminoma were treated with the VIP-regimen consisting of vinblastine 6 mg/m2 days 1+2, ifosfamide 1.5 g/m2 days 1-5, cisplatin 20 mg/m2 days 1-5. One patient showed primary progression, another patient partial remission, and one patient died during the first cycle. All the other patients had complete remission (21/24 = 87%), which was documented histologically in 9 patients. One patient relapsed but obtained complete remission after repeated treatment. Thus 21 patients are currently living without disease after a median observation time of 30+ months. Bone marrow toxicity was severe, leading to dose reduction in more than 50% of the patients. No other severe side effects were observed. We conclude that the regimen is highly effective in bulky seminoma. Reduction of the vinblastine dose is recommended because of bone marrow toxicity.

Adult↗
PubMed2006

Brief communication: sirolimus-associated pneumonitis: 24 cases in renal transplant recipients.

BACKGROUND: Interstitial pneumonitis is an ill-defined side effect of sirolimus, a new immunosuppressant drug recently introduced for patients having organ transplantation. OBJECTIVE: To evaluate clinical and laboratory features of sirolimus-associated pneumonitis. DESIGN: Case series. SETTING: 1 transplantation center in Paris, France. PATIENTS: 24 patients who had renal transplantation and developed sirolimus-associated pneumonitis, including 8 patients previously reported. MEASUREMENTS: Symptoms; laboratory tests, including bronchoalveolar fluid analysis; and computed tomography (CT) of the chest. INTERVENTION: Withdrawal or dose reduction of sirolimus. RESULTS: Clinical symptoms included cough (23 patients), fatigue (20 patients), fever (16 patients), and dyspnea (8 patients). Computed tomography of the chest showed reticular and ground-glass opacities (4 patients), bronchiolitis obliterans-organizing pneumonia (19 patients), and lobar consolidation (1 patient). Bronchoalveolar lavage showed lymphocytic (19 patients) or eosinophilic (3 patients) alveolitis or pulmonary hemorrhage (2 patients). A reduction in the sirolimus dose resulted in transient clinical improvement in 2 patients, but discontinuation of drug therapy was eventually necessary in all patients. All patients recovered completely within 6 months. LIMITATIONS: The sirolimus trough level in patients from this single center was higher than that usually used in patients having renal transplantation. CONCLUSION: Lymphocytic alveolitis and radiologic bronchiolitis obliterans-organizing pneumonia are the key findings in sirolimus-associated pneumonitis. Sirolimus withdrawal was associated with recovery within 6 months.

Adult↗
PubMedDate not supplied

Oxaliplatin plus raltitrexed in the treatment of patients with advanced colorectal cancer: a phase II study.

UNLABELLED: The combination of Oxaliplatin (OXA) and Raltitrexed (RTX) may represent a more convenient regimen as compared with OXA + 5-FU with Folinic acid (FA) modulation regimens. The present trial has been designed to explore the activity and tolerability of this combination in untreated and pretreated patients with advanced colorectal cancer (ACC). OXA and RTX were administered at the dose of 130 mg/m2 as i.v. 3-hour infusion and 3 mg/m2 over a 15-minute i.v. infusion, respectively, repeated every 21 days. Fifty patients were enrolled between February 1999 and March 2001. A total of 293 cycles were administered, with a median number of 6 cycles (range 1-14) per patient. The median dose intensity for OXA and RTX was 100% (50-100) and 86% (21-100), respectively. Reasons for RTX dose reduction were increases in transaminase serum levels and a reduction in creatinine clearance. Myelotoxicity was limited. A transaminase increase was observed in 74% of patients (14% grade 3 and 10% grade 4). Peripheral sensorial neurotoxicity was the most frequent side-effect (88%), although its intensity was mild in most patients (grade I 48%, grade II 24%, grade III 16%). Of 46 evaluable patients, 3 CR, 5 PR, 22 S and 16 P were observed. The CR + PR remission rate, according to the intention to treat analysis, was 16% with a 95% confidence limit of 7.2%-29.1%; in patients not pretreated for advanced disease the CR + PR rate was 26%, while only 2 out of 27 pretreated patients responded to the treatment (7%). The median time to progression was 5 months (2-11). The median survival was not reached after a median follow-up of 14 months. One-year survival is 60%. CONCLUSION: In this trial the OXA + RTX combination is confirmed to be active in ACC, although the level of activity seems to be lower than that of the other combination including OXA and 5-FU with or without FA modulation. The reasons for the low activity observed could at least in part be related to a reduction in the RTX dose intensity.

Adult↗
PubMed1998

Management of high-risk gestational trophoblastic disease.

Multimodality therapy with combination chemotherapy employing etoposide, high-dose methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO), and adjuvant radiotherapy and surgery, when indicated, has resulted in cure rates of 80-90% in patients with high-risk metastatic gestational trophoblastic tumors. However, approximately 25-30% of high-risk patients will have an incomplete response to first-time chemotherapy or will relapse from remission. Most of these patients will have a clinicopathologic diagnosis of choriocarcinoma, metastases to sites other than the lung and vagina, more than eight metastases and/or failed inappropriate previous chemotherapy, resulting in very high World Health Organization scores. Salvage chemotherapy with cisplatin/etoposide, usually in conjunction with bleomycin or ifosfamide, as well as surgical resection of sites of resistant disease in selected patients, will result in a cure in most patients. New technology, such as the use of colony-stimulating factors to prevent treatment delays and dose reductions or high-dose chemotherapy with or without autologous bone marrow transplantation or peripheral blood stem cell support, may play an important role in the future management of patients who develop drug resistance.

Antineoplastic Combined Chemotherapy Protocols↗