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PubMed1999

Phase II study of vinorelbine and gemcitabine for inoperable stage IIIB-IV non-small-cell lung cancer.

PURPOSE: To evaluate the efficacy of the combination of vinorelbine and gemcitabine as a non-platinum chemotherapy regimen in patients with inoperable locally-advanced or metastatic non-small-cell lung cancer (NSCLC). Efficacy was assessed primarily in terms of response rate, and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Patients with cytologically- or histologically-proven stage IIIB-IV NSCLC, bi-dimensionally measurable lesions, adequate haematological, hepatic and renal function, WHO performance status < or = 2 and no previous chemotherapy or radiotherapy were eligible. The first 12 patients were entered in a pilot study and received vinorelbine (VNR) 30 mg/m2 on days 1, 8, 15 and 22, and gemcitabine (GEM) 1000 mg/m2 on days 1, 8 and 15, of a 28-day cycle. Subsequently, patients were entered in a phase II trial of VNR 35 mg/m2 and GEM 1200 mg/m2 on days 1 and 15 of each 28-day cycle. Treatment consisted of three cycles of the chemotherapy, with a further three cycles for those patients who achieved stable disease or a complete or partial response (CR/PR) to the first three cycles. Patients who had achieved CR or PR after six cycles continued with the treatment until relapse. RESULTS: The dosage and scheduling of VNR and GEM in the pilot study resulted in neutropenia necessitating reductions or delays in treatment, and consequently low dose intensity. The schedule was thus modified to VNR 35 mg/m2 and GEM 1200 mg/m2 on days 1 and 15 of each 28-day cycle for the phase II trial. Thirty-three patients were enrolled in the phase II trial, and 28 were evaluable for response. The overall intent-to-treat response rate of all 45 patients was 40% (18 of 45), comprising 4 CR (9%) and 14 PR (31%). For the 28 evaluable patients who received the fortnightly chemotherapy the response rate was 46% (13 of 28), CR 11% (3 of 28) and PR 36% (10 of 28). Seven patients (25%) had stable disease. The one-year cumulative survival rate for the 33 patients receiving the fortnightly chemotherapy was 24% and median time-to-progression 4 months (range 1-16 months). Median survival for these patients was eight months. Nine out of twelve patients in the pilot study (75%) suffered grade 3-4 neutropenia. There was one toxic death, attributed to neutropenic fever and sepsis, and two cases of pulmonary embolism. One patient suffered Grade 4 thrombocytopenia. Only eight patients (24%) on the fortnightly schedule suffered grade 3-4 neutropenia, resulting in dose reductions or delays for three of them (9%). None of the patients on the fortnightly schedule suffered thrombocytopenia or anaemia. CONCLUSIONS: The fortnightly schedule of gemcitabine and vinorelbine was a well-tolerated out-patient regimen, producing response and survival rates comparable to those of cisplatin combination regimens, but with a more favourable toxicity profile. Gemcitabine and vinorelbine should now be tested in a triplet combination with a taxane as the third drug, or against a platinum-containing regimen in a phase III study.

Adult↗
PubMed1997

Nasal administration of retinal antigens maintains immunosuppression of uveoretinitis in cyclosporin-A-treated Lewis rats: future treatment of endogenous posterior uveoretinitis?

PURPOSE: Current treatment of autoimmune endogenous posterior uveoretinitis (EPU) is limited by drug toxicity, unpredictable relapses on dose reduction and resistance to therapy. Administration of autoantigens via gastrointestinal or respiratory mucosa prior to antigen exposure induces immune hyporesponsiveness (mucosal tolerance) to further antigen sensitisation. In this study we assessed whether mucosal tolerance induction was possible after immunisation with retinal antigens in experimental autoimmune uveoretinitis (EAU) in animals that were short-term immunosuppressed with cyclosporin A (CsA) to determine whether mucosal administration of retinal antigens can maintain immunosuppression in sensitised and immunosuppressed individuals. METHODS: Female Lewis rats were immunised with retinal extract (RE) and then treated as follows. Group 1 received no specific therapy and served as control; group 2 were fed CsA from day 7 to day 20 post-immunisation; group 3 received inhalational tolerance therapy with RE in addition to CsA; tolerance therapy was continued after day 20 when CsA was stopped. Experiments varying the timing and dosage of both tolerising and immunising antigen were also performed, the details of which are described. Incidence, day of onset and clinical activity were recorded and histopathological assessment of intraocular inflammation, in particular the extent of autoimmune target-organ damage, was graded semiquantitatively. RESULTS: Compared with controls and group 2, group 3 showed both a marked delay in disease onset and a reduction in disease severity. This effect was both dose and dose-timing dependent. Tissue damage assessed in terms of preservation of rod outer segments was significantly less in group 3. CONCLUSIONS: The success of combination therapy, clinically, remains unknown at present but these results support continuing present clinical trials of mucosal tolerance therapy and in particular have future implications for either maintaining or inducing immunosuppression in autoimmune diseases in combination with present immunosuppressive therapies.

Administration, Intranasal↗
PubMed2004

Dose intense triplet chemotherapy with gemcitabine, carboplatin, paclitaxel with peripheral blood progenitor cell support for six cycles in advanced epithelial ovarian cancer.

The interval required for haematological reconstitution following myelosuppressive chemotherapy can be reduced by the infusion of autologous peripheral blood progenitor cells (PBPCs). When carboplatin (C) and paclitaxel (P) are followed by granulocyte colony-stimulating factor (GCSF), multiple courses can be given at 10-day intervals with the autologous PBPCs from a unit of whole blood with each cycle. We extended this approach and defined the dose-limiting toxicity and maximum-tolerated dose for the addition of gemcitabine (G) to CP for patients (pts) with EOC in a phase I-II study of increasing doses of G (0, 800, 1000 and 1250 mg x m(-2)) over four cohorts with C at area under curve (AUC) 6, plus P at 175 mg x m(-2) 3 h(-1) every 10 days for six cycles. Granulocyte colony-stimulating factor 5 microg x kg(-1) day(-1) was given s.c. days 1-10 and 450 ml whole blood was venesected before each treatment, stored untreated at 4 degrees C and reinfused 24 h later. In all, 17 patients with EOC either bulky stage IV or recurrent after treatment-free interval >12 months were treated over 30 months. Of the 17 patients, 13 completed six cycles (one patient stopped early with PD, three with toxicity), interdose interval 9-28 (median 10) days. Delays occurred in four patients due to infection or malaise, and there were no dose reductions. Haematological toxicity was not considered to be dose limiting. Febrile neutropenia was uncommon (2 patients), but grade III/IV thrombocytopenia was seen across all cohorts. Treatment was not delayed for thrombocytopenia and no bleeding complications occurred. Grade III transaminitis was seen in all patients in cohort 4 and grade IV toxicity, considered to be dose limiting, occurred in one. Responses were observed at all dose levels with six CR, seven PR, three SD and one PD. Dose intense GCP was deliverable over six cycles with manageable haematological toxicity, but with dose-limiting hepatic toxicity in cohort 4. The MTD was gemcitabine 1000 mg x m(-2), carboplatin AUC 6, paclitaxel 175 mg x m(-2) given every 10 days for six cycles.

Adolescent↗
PubMed2004

Evaluation of the radioprotective effect of bael leaf (Aegle marmelos) extract in mice.

PURPOSE: To investigate the radioprotective activity of a leaf extract of bael leaf (Aegle marmelos) (AME) in mice exposed to different doses of gamma-radiation. MATERIALS AND METHODS: The acute toxicity of AME was evaluated in Swiss albino male mice administered various intraperitoneal single doses of AME. For radioprotection studies, mice were administered different doses, 0, 5, 10, 15, 20 or 40 mg kg(-1), of AME or sterile physiological saline intraperitoneally once daily consecutively for 5 days before exposure to 10 Gy 60Co gamma-radiation or five doses of 15 mg kg(-1) AME before exposure to 6, 7, 8, 9, 10 or 11 Gy. The animals were monitored for symptoms of radiation sickness and mortality up to 30 days post-irradiation. Glutathione and lipid peroxidation were estimated in the surviving animals of both groups on day 31 post-irradiation. RESULTS: AME was non-toxic up to a single dose of 1750 mg kg(-1). The optimum radioprotective dose was five consecutive doses of 15 mg kg(-1) AME, where the highest survival to 10 Gy radiation was observed. The irradiation caused a dose-dependent decline in survival, while treatment of mice with AME enhanced survival. The dose reduction factor was 1.15. Irradiation caused a dose-dependent decline in the level of glutathione accompanied by an elevation in lipid peroxidation. AME pretreatment arrested glutathione decline and lipid peroxidation significantly. CONCLUSION: AME treatment reduced the symptoms of radiation-induced sickness and increased survival. The radioprotective action might be due to free-radical scavenging and arrest of lipid peroxidation accompanied by an elevation in glutathione.

Aegle↗
PubMed2005

Imaging dose management using multi-resolution in CT-guided radiation therapy.

In image-guided radiation therapy, megavoltage computerized tomography (MVCT) delivers higher dose to the patient for lower image quality than diagnostic kilovoltage CT (kVCT). One way to reduce the mean imaging dose is to reduce the imaging volume, which is often sufficient for registration and dosimetry purposes. The filtered back projection using truncated data causes artefacts that degrade the image quality. Those artefacts can be effectively reduced by wavelet-based multi-resolution analysis (WMRA), in which the detail and approximate information are reconstructed separately to bypass the non-locality of filtered back projection. In this study, WMRA was used to reconstruct local images from both very low-dose kVCT scans from a bench-top tomotherapy unit and MVCT scans from helical tomotherapy. Results show that mean imaging dose can be significantly reduced by imaging a small region of interest. In simulation, the root-mean-square error brought by the truncation is smaller than 1-2% and depends on the level of dose reduction. On the other hand, the same mean dose that would have been delivered by a low-quality global CT can be conformed to a smaller volume to improve the visibility of low-contrast organs and fine structures using WMRA. Organs at risk can be avoided during repeated daily CT imaging when irregular-shaped reconstruction areas are used. WMRA does not involve computationally expensive iterations and is suitable for image-guided radiation therapy where imaging speed is essential. Compared with extrapolation methods, errors are further reduced to improve the detection of low contrast and fine structures.

Algorithms↗
PubMed1992

Chemotherapy of cervix cancer with mitolactol (dibromodulcitol, NSC 104800) and cisplatin. A phase I study of the Gynecologic Oncology Group.

In this Phase I study, thirteen women with advanced cervix cancer were treated with mitolactol (dibromodulcitol) plus cisplatin to determine a maximum tolerable dose schedule. Response was not an objective of this study, but four partial responses were seen in nine patients with measurable lesions. In general, the therapy was well tolerated, but of the ten patients treated at the first dose level (cisplatin 50 mg/m2 intravenously on day 1 plus mitolactol 180 mg/m2 orally on days 2-6 every 3-4 weeks), 5 required de-escalations and 8 required delays because of toxicity. All three patients treated with cisplatin plus a higher dose of mitolactol (270 mg/m2 x 5) required dose reductions and delays for hematologic toxicity. The first dose level appears tolerable by patients with, and promising in treating, advanced cervix cancer.

Adult↗
PubMed2002

Gastrointestinal pneumatosis after docetaxel chemotherapy.

Breast cancer is one of the most frequent neoplasms in women. New drugs, including taxanes, have improved survival in patients with metastatic disease. Quality of life and efficacy are important goals during treatment of these women. Herein, we report a 51 year-old woman with metastatic breast cancer who developed gastrointestinal pneumatosis (GIP) after the first cycle of treatment, which consisted of docetaxel and pamidronate. The symptoms disappeared after 7 days with supportive management, nasogastric intubation, parenteral fluids, and wide-spectrum antibiotics. Thereafter, weekly fractionated chemotherapy with an initial 50% dose reduction was administered. Because of adequate tolerance, the dose was increased by 25% after the second cycle, and full-dose docetaxel was administered after the third cycle. After 6 months of follow-up, the patient remained under treatment, with an Eastern Cooperative Oncology Group performance status of 1. Gastrointestinal pneumatosis has been reported in association with chemotherapy. In most patients, it is reported to be associated with neutropenia, which was not present in this patient.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients.

A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady-state heroin treatment for at least 12 months. For safety reasons, there was no crossing-over between heroin injection or inhalation. In a double-blind randomised study, 67-100-150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6-monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS-MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels were inversely related to creatinine clearance. After heroin administration, the reaction time was significantly prolonged with 28+/-5.3 msec. in injecting and 13+/-4.9 msec. in inhaling patients. Cardiovascular changes were only mild after heroin administration. Craving-scores declined immediately after heroin administration in both administration groups. Subjective heroin effect was rated more positively in heroin inhaling than in injecting patients, despite the lower C(max) levels following heroin inhalation. In both groups, in this blinded study heroin dose increments were more appreciated than dose reductions. Increments of 50% of the regular heroin dose did not cause any serious side effect.

Administration, Inhalation↗
PubMed1992

Double blind dose-response study of zidovudine in AIDS and advanced HIV infection. Nordic Medical Research Councils' HIV Therapy Group.

OBJECTIVE: To compare the efficacy and side effects of 400 mg, 800 mg, and 1200 mg zidovudine daily in patients with AIDS or advanced HIV infection. DESIGN: Randomised, double blind, parallel group multicentre study. SETTING: Hospital departments of infectious diseases and dermatology in Denmark, Sweden, Norway, Finland, and Iceland. SUBJECTS: 474 patients: 126 (27%) with AIDS; 248 (52%) with HIV related symptoms; 100 (21%) with low CD4+ cell counts. INTERVENTIONS: Zidovudine 400 mg (160 patients), 800 mg (158), or 1200 mg (156) daily. All patients received one capsule from each of three bottles four times daily. MAIN OUTCOME MEASURES: Survival; incidence of new HIV related events; CD4+ cell count; quality of life; incidence of haematological side effects. RESULTS: 460 (97%) of the 474 patients had not received zidovudine previously. The median follow up period was 19 months, during which the death rates in the three treatment groups were 23% (36/160 patients), 23% (36/158), and 19% (30/156) respectively (p = 0.49; log rank test). One year after the trial was terminated the death rates were 38% (61/160), 41% (64/158), and 44% (68/156) respectively (p = 0.54). There was no significant difference between the groups in time to a new AIDS defining event or death, average number of events per patient, decline in CD4+ cell counts, wellbeing (visual analogue scale), or Karnofsky score. Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related. CONCLUSION: Zidovudine should be limited to 400-600 mg daily in patients with AIDS or advanced HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Radiation exposure at chest CT: a statement of the Fleischner Society.

The introduction of helical single-detector row computed tomography (CT) and, more recently, multi-detector row CT has greatly increased the clinical indications for CT. Correspondingly, CT examinations now account for greater than one-half of the radiation dose due to medical procedures in the population of North America. The level of CT radiation dose, especially in the pediatric population, is of concern to radiologists, medical physicists, government regulators, and the media. This review addresses this problem with particular reference to radiation dose in chest CT. Specifically it outlines the topics of measurement units used to quantify radiation exposure, factors affecting CT scanner dose efficiency, scanner settings that determine the administered radiation dose, and radiation dose reduction in chest CT. A table of reference dose values is provided. Given the wide variation documented in chest CT radiation exposure, the authors suggest that reference standards be promoted to minimize excessive CT radiation exposure. In addition, further research into the complex relationship between radiation exposure, image quality, and diagnostic accuracy should be encouraged in order to establish the minimum radiation dose necessary to provide adequate diagnostic information for standard clinical questions.

Child↗
PubMed2001

Intracranial germinoma: radiation therapy with tumor volume-based dose selection.

PURPOSE: To prospectively investigate whether intracranial germinomas, except large ones, can be cured with radiation doses lower than 50 Gy and to determine 10-year follow-up results. MATERIALS AND METHODS: Between 1985 and 1995, 38 patients with intracranial germinoma diagnosed histologically or with established criteria were enrolled. Total radiation doses to the primary tumor site were 36 Gy after total removal, 40 Gy for tumors less than 2.5 cm in diameter, 45 Gy for those 2.5-4.0 cm, and 50 Gy for those greater than 4.0 cm, with 1.6-1.8-Gy daily fractions. Patients underwent irradiation of the primary tumor site or cerebrospinal axis (20-24 Gy), depending on findings at diagnosis. No chemotherapy was allowed. RESULTS: All patients completed radiation therapy. Thirty-five patients were treated according to protocol, and three with relatively slow tumor regression or presence of a cyst received additional radiation (5-7 Gy, 50-52 Gy total). Ten-year overall and relapse-free survival rates were 91% and 95%, respectively. Two patients developed meningeal dissemination, but none had local failure. Treatment complications included chordoma in one patient and internal carotid artery occlusion in another. No treatment-related decline of performance status was observed in the other patients. CONCLUSION: All tumor volume-based radiation doses were effective, without risk of local failure. Intracranial germinoma 4 cm or less in diameter can be cured with doses of 40-45 Gy. Investigation of further dose reduction seems worthwhile. Radiation therapy alone with these doses should be compared with ongoing chemotherapeutic protocols plus low-dose (24-30-Gy) irradiation in future studies.

Brain Neoplasms↗
PubMed2002

High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study.

With the intention of starting an international protocol between Italy and Scandinavia on neoadjuvant treatment of extremity osteosarcoma using the four active drugs at maximum doses (doxorubicin 75 mg/m2 pre-operatively, and 90 mg/m2 post-operatively, cisplatin 120 mg/m2, methotrexate 12 g/m2, and ifosfamide 15 g/m2), a single center (the Rizzoli institute) performed a pilot study to closely monitor toxicity, safety, and tumor necrosis. Only 7 patients (10%) had a reduced number of the scheduled cycles. A total of 1,050 of the expected 1,076 cycles (98%) were administered. Delays and dose reduction were minimal, leading to a mean received dose intensity of 89%. Limb salvage surgery was performed in 59 cases (87%), with 6 amputations and 3 rotation plasties. Chemotherapy-induced necrosis higher than 95% was observed in 38 patients (56%). Eleven patients had total necrosis (16%). At a median follow-up of 60 months (range 50-65 months), 53 patients (73%) were continuously disease-free. Six of the relapsed patients were rescued with further treatments leading to an overall survival of 87%. Hematological toxicity was remarkable despite the use of G-CSF and hospitalization due to febrile neutropenia occurred in 25 patients (37%). Platelet transfusions were required in 77 of the 194 episodes of grade 4 thrombocytopenia, but no case of major bleeding was observed. Red blood cell transfusions were necessary in all patients (in 15 cases perioperatively only). Non-hematological toxicity comprised grade 1-2 nephrotoxicity in 3 cases, CNS toxicity in 2 cases, and dilata- tive cardiopathy leading to heart transplantation in 1 case. In conclusion, the pilot study was feasible in the vast majority of cases with toxicity not superior to that of the previous protocols where chemotherapy was given in lower doses. The rate of limb salvage procedures, event-free survival and overall survival seemed to be higher than in previous protocols. On the basis of this study, in March 1997 the Italian and Scandinavian Sarcoma Groups started a new protocol for osteosarcoma of the extremities.

Adolescent↗
PubMed1984

Toxic deaths in the Second National Wilms' Tumor Study.

There were 122 deaths among 803 children registered, randomized, and followed in the second National Wilms' Tumor Study; 17 occurred in children apparently free of disease and were attributable to causes other than tumor progression. Seven deaths were attributed to infection during periods of drug-induced leukopenia; four were due to liver failure; and one each was attributable to radiation pneumonopathy, intestinal obstruction, renal failure, myocardial disease, and encephalopathy. The cause of one death was unexplained. Of particular concern were four (of 47) infants under one year of age with group I or II disease who had toxic deaths. Subsequent to these experiences the doses of all chemotherapeutic agents were reduced by 50% for infants under one year of age. No deaths from toxicity were observed thereafter in infants. An analysis of the therapeutic effect of this dose reduction showed three of 47 relapsed on full dose and five of 54 on half dose. The difference is not statistically significant. This report is a further demonstration of the potentially serious vulnerability of infants to standard doses of anticancer drugs even when they are calculated on a per kilogram basis.

Age Factors↗
PubMed1993

Dose-ranging study of oxycodone for chronic pain in advanced cancer.

PURPOSE AND METHODS: We assessed the analgesic efficacy and safety of single-entity oxycodone solution at doses greater than 10 mg orally every 4 hours in 24 patients with chronic cancer pain not controlled by weaker analgesics. RESULTS: Twenty of 24 patients completed the study. Pain relief was obtained with doses up to 60 mg every 4 hours. When oxycodone was taken for long periods, further dose increments could be made safely. The side effects of oxycodone are mild, and common to all opioids, with sedation and constipation most frequent. Nausea was more common in females in all age groups and in patients of either sex less than 50 years of age. Episodes of serious toxicity were rare, and responded to dose reduction. Patients older than 65 years required lower doses, suggesting pharmacokinetic similarities between oxycodone and morphine. Patients changed from oral oxycodone to morphine remained pain-free when relative milligram potency ratios of 1:1 to oral morphine and 3:1 to intravenous morphine were used. CONCLUSION: Oxycodone has been shown for the first time to be as versatile and flexible as oral morphine in the management of chronic pain in patients with advanced cancer.

Adult↗
PubMed2001

Phase I/II study of escalating doses of vinorelbine in combination with oxaliplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: Oxaliplatin is a platinum compound active in non-small-cell lung cancer (NSCLC) patients, and vinorelbine (VNB) is an active reference agent. This phase I/II study was performed to determine the dose-limiting toxicity (DLT), the maximum-tolerated dose (MTD), and the recommended dose (RD) of a VNB/oxaliplatin combination given to previously untreated patients with advanced NSCLC. PATIENTS AND METHODS: Oxaliplatin was given at the fixed dose of 130 mg/m2 (2-hour intravenous [IV] infusion) on day 1. VNB was administered on days 1 and 8 (10-minute IV infusion), with doses starting at 22 mg/m2/d and escalated by 2 mg/m2 increments until MTD. Treatment was repeated every 3 weeks. No special hydration measures or prophylactic granulocyte colony-stimulating factors were used. RESULTS: Twenty-seven patients (20 men, 7 women) received 110 cycles total at six different VNB dose levels. Neutropenia was the DLT. Although no patient experienced DLT at the highest dose level (32 mg/m2/d), multiple treatment delays (54% of cycles) and dose reductions (34% of cycles) were required at this dose level. Others toxicities were mainly limited to grade 1 peripheral neuropathy and grade 1/2 nausea/vomiting. The relative dose-intensity of administered VNB from dose levels 3 to 6 (26 to 32 mg/m2) remained stable, whereas grade 3/4 neutropenia increased. All patients were assessable for activity; there were 10 objective responses, including one complete response (37% response rate). CONCLUSION: The present combination can be safely administered in an outpatient setting. The RD is VNB 26 mg/m2 days 1 and 8 with oxaliplatin 130 mg/m2 day 1 every 3 weeks.

Adult↗
PubMed1988

Lead thickness in shielding in the protection of radiodiagnostic staff.

We indicate the principles which can be used to apply cost-benefit analysis to radiation protection of staff in an X-ray department. The cost of saving radiation exposure to staff by varying the lead equivalence of lead gowns and lead protective screens is calculated. The cost is compared with the financial values of the detriment as assessed by the National Radiological Protection Board. The expenditure required to avoid a man-Sv for staff protection in diagnostic departments is suggested. In the examples we take, it is found that the larger staff dose reductions, and often the cheaper reductions, can be obtained by reducing the radiation dose to the patient. There are, of course, major additional advantages to the patient in reducing this dose.

Cost-Benefit Analysis↗
PubMed2001

A computer model of an image intensifier system working under automatic brightness control.

A computer model of a fluoroscopy unit operating under automatic brightness control has been developed. The model has been validated by simulating one particular unit but is very general in nature and can easily be applied to other fluoroscopy systems. The model was developed by breaking the operation of a fluoroscopy unit down into its constituent parts then implementing each part in a module of code. It is controlled using the input air kerma to the intensifier face. Discrepancies from the situation when the model is controlled by the energy deposited in the input phosphor have been investigated and shown to be negligible over the operating range. To calculate entrance surface dose rates (ESDRs) to water and polymethylmethacrylate (PMMA) phantoms, Monte Carlo techniques were used to generate backscatter factors for these materials using the beam geometry and range of possible tube potentials and field sizes of a typical mobile image intensifier unit. The model was validated by calculating ESDRs to different thicknesses of water and PMMA phantoms. The predictions generated by the model were in good agreement with experimental measurements. Potential uses of the model include evaluation of dose reduction techniques, investigation of the balance between patient dose and image quality, and assessment of scatter dose.

Algorithms↗
PubMed2005

Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: an integrated analysis.

The purpose was to conduct an integrated analysis of the cumulative hematologic toxicity of topotecan in patients with relapsed ovarian cancer and small cell lung cancer (SCLC). Data were pooled from eight phase II and phase III clinical studies performed in patients with relapsed stage III/IV ovarian cancer or extensive SCLC treated with topotecan at a dose of 1.5 mg/m(2) per day on days 1-5 of a 21-day course. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. A total of 4,124 courses of therapy was administered to the 879 patients in the pooled population. Grade 4 neutropenia was experienced by 78% of patients. The lowest nadirs for neutrophils and platelets generally occurred after the first course of therapy, followed by improvement or stabilization in subsequent courses. Neutropenia was noncumulative. During the first course, significant risk factors were identified: renal impairment and advanced age (grade 3/4 thrombocytopenia and grade 4 neutropenia) and prior radiotherapy; performance status score > or =2; SCLC; and exposure to both cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb) (grade 3/4 thrombocytopenia only). The most frequent interventions for hematologic toxicities were RBC transfusions, treatment delays, G-CSF support, and dose reductions. Analysis of neutrophil and platelet nadirs and dosing for each course of therapy showed no apparent evidence of cumulative neutropenia or thrombocytopenia. The risk of grade 3 or 4 anemia was higher during the first four courses of therapy and may need to be more aggressively managed with erythropoietin therapy.

Antineoplastic Agents↗