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PubMed1997

Methotrexate use in systemic lupus erythematosus.

Low dose pulse oral methotrexate (MTX) is a well established treatment for rheumatoid arthritis, and short term open studies have suggested beneficial effects of MTX in SLE. This study was designed to investigate MTX treatment maintenance rates in SLE using life table analysis, and to determine whether MTX use was associated with a dose reduction of concomitant steroid therapy. All SLE patients managed by physicians affiliated with a single centre were studied cross-sectionally. Information regarding disease variables and drug use were ascertained by interview and chart review. Drug therapy data including dates of treatment and indications for treatment were analysed using Kaplan-Keier life table methods. Among 101 subjects with SLE, 25 MTX treatment episodes were observed in 24 subjects. The period studied totalled 19766 patient-days, with a median (range) duration of observed MTX treatment of 14.4 (5.1-41.6) months. The median (range) initial and peak MTX doses with 7.5 (2.5-10)mg/wk and 10 (7.5-15) mg/week respectively. The principal indication for commencing methotrexate therapy was arthritis. Only two subjects terminated treatment for toxicity, with the most common reason for termination being remission. The cumulative probability of continuing treatment was 68% at 12 months and 61% at 24 months, or 75% and 71% respectively if cessations for remission were excluded. The median (interquartile range) monthly steroid intake during MTX therapy [279.4 (193.4-492.9)mg] was somewhat lower than during the 6 months prior to [298.1 (237.9-531.4)428.8)mg] MTX therapy, but this difference was not significant. A total of 36% of subjects reduced their steroid dose during MTX therapy, but this reduction was not significant. Treatment of SLE with MTX, predominantly for arthritis, was well tolerated over prolonged periods of observation. Toxicity of sufficient severity to lead to treatment termination was uncommon. A subset of subjects were able to reduce steroid intake during MTX therapy, but no overall reduction in steroid dose was observed.

Adult↗
PubMed2002

Potential cost savings of erythropoietin administration in end-stage renal disease.

BACKGROUND: In a Department of Veterans Affairs randomized controlled trial, a lower dose of recombinant human erythropoietin (epoetin) was shown to attain target hematocrit levels when administered subcutaneously compared with intravenously. Since epoetin is expensive, optimizing the therapeutic effect of epoetin using a strategy that includes subcutaneous administration could lead to substantial cost savings. METHODS: We used an economic cost projection model to estimate potential savings to the Medicare End-Stage Renal Disease Program that could occur during a transition from intravenous to subcutaneous administration of epoetin among hemodialysis patients. Data included clinical results from the Department of Veterans Affairs randomized controlled trial, the 1998 Centers for Medicare and Medicaid Services' End-Stage Renal Disease Core Indicators Survey, and the 1997-1998 Medicare claims files. In sensitivity analyses, we varied the expected dose reductions (10% to 50%) and the proportion of patients (25% to 100%) who switched to subcutaneous administration. RESULTS: Medicare cost savings were estimated at $47 to $142 million annually as 25% to 75% of hemodialysis patients who received epoetin intravenously switched to subcutaneous administration while reducing the dose by 32%. A minimal reduction (10%) in epoetin dose would result in Medicare cost savings of an estimated $15 to $44 million annually. CONCLUSION: Administering epoetin subcutaneously would provide substantial cost savings to Medicare. For the transition to occur, consensus among stakeholders is needed, especially among patients whose treatment satisfaction and health-related quality of life would be most affected.

Costs and Cost Analysis↗
PubMed2006

Assessment of tube current modulation in pelvic CT.

An anatomically shaped polymethylmethacrylate (PMMA) phantom was used to assess the effect of the Siemens CARE Dose mA modulation system on pelvic CT scans. The effect of the system on absorbed dose to air, image percentage noise and the signal to noise ratio of clinically relevant details was assessed. The signal to noise ratio was calculated using Polytetrafluoroethylene (PTFE) and distilled water inserts; PTFE was used to represent bony structure and distilled water was used to represent soft tissue abscess. Pelvis protocols identified from local hospitals and the UK CT Dose Survey (2002), were assessed and compared with those provided by Siemens Medical (UK). These protocols were tested on a Siemens Sensation 4 CT scanner, both with and without CARE Dose. Results were obtained which showed that dose savings were possible with no significant increase in image noise. Dose reductions were 8% in the lateral positions in the phantom and 42% in the centre, top and bottom. The calculated "CTDIvol" was 32% lower with CARE Dose than without CARE Dose. This is slightly greater than the 25% change in the effective mAs values that was found. This implies that the reduction in the effective mAs values is a reasonable predictor of the total reduction in absorbed dose to air, whilst slightly underestimating the actual change. The results also showed a non-significant trend towards decreased signal to noise ratios for clinically relevant CT numbers when CARE Dose was activated. This suggests that tube current modulation may detrimentally affect signal detection due to changes in image noise.

Equipment Design↗
PubMed1999

Calculated effects of displacement errors in external beam radiotherapy of prostatic adenocarcinoma.

In order to evaluate the impact on the biological effective dose (BED) of irradiation delivered to a tumour with large displacement errors (LDE) and to estimate the effect on local control, simulated treatment of prostatic adenocarcinoma was performed. The calculation of BED in combination with the critical-voxel model and the LQ model was used to evaluate the effect of different combinations of LDEs. The model is called the Dose Volume Inhomogeneity Corrected BED (DVIC-BED) model. The dose-response curve was assumed to follow Poisson statistics. Different combinations of radiobiological parameters were used to test the model. A simulated clinical treatment with a dose of 66-80 Gy in 2 Gy fractions was carried out to evaluate displacement errors and non-optimal dose distributions. Five random LDEs excluding 33% of the target volume corresponded to an overall dose reduction of 3-5 Gy compared with a 10 Gy reduction if 100% of the target is missed five times. A 5 Gy decrease in dose corresponds to a reduction in clinical or chemical control up to 10-25% in the interval 65-85 Gy. LDEs in different directions are less deleterious than errors occurring in the same direction. Different alpha/beta-ratios (3-15) had little effect on the DIC-BED, but the effect of different alpha values (0.05, 0.2 and 0.5) was large. However, the results depend on radiobiological parameters for prostatic adenocarcinoma, which not are well known, and further studies in the field should be encouraged.

Adenocarcinoma↗
PubMed2006

Quantitative assessment of selective in-plane shielding of tissues in computed tomography through evaluation of absorbed dose and image quality.

This study aimed at assessment of efficacy of selective in-plane shielding in adults by quantitative evaluation of the achieved dose reduction and image quality. Commercially available accessories for in-plane shielding of the eye lens, thyroid and breast, and an anthropomorphic phantom were used for the evaluation of absorbed dose and image quality. Organ dose and total energy imparted were assessed by means of a Monte Carlo technique taking into account tube voltage, tube current, and scanner type. Image quality was quantified as noise in soft tissue. Application of the lens shield reduced dose to the lens by 27% and to the brain by 1%. The thyroid shield reduced thyroid dose by 26%; the breast shield reduced dose to the breasts by 30% and to the lungs by 15%. Total energy imparted (unshielded/shielded) was 88/86 mJ for computed tomography (CT) brain, 64/60 mJ for CT cervical spine, and 289/260 mJ for CT chest scanning. An increase in image noise could be observed in the ranges were bismuth shielding was applied. The observed reduction of organ dose and total energy imparted could be achieved more efficiently by a reduction of tube current. The application of in-plane selective shielding is therefore discouraged.

Humans↗
PubMed1996

A linear quadratic analysis of gynaecological brachytherapy.

Four hundred and fourteen patients were treated by radical radiotherapy alone for cervical carcinoma at the Western Infirmary and the Royal Beatson Memorial Hospital between April 1982 and December 1987. All patients received external beam radiotherapy in addition to brachytherapy, using either manually inserted caesium (n = 107) or the Selectron afterloading machine (n = 307). Three mean Selectron dose rates were used: 0.91 Gy/h, 1.195 Gy/h and 1.74 Gy/h. During this period of time, the cumulative radiation effect formula was used to calculate an overall brachytherapy dose reduction to compensate for the increase in point 'A' dose rate. We have compared the local control rates and the incidence of late effects seen in these patients with theoretical parameters calculated using the linear quadratic (LQ) model. This model predicts a small rise in late effects as the dose rate increases, which is also seen in clinical practice; it also predicts a reduction in local control, partially offset by the addition of external beam radiotherapy, which would be most marked for early stage disease. There was a small fall in local control associated with Selectron treatment, but of a smaller size than predicted by the LQ model.

Algorithms↗
PubMed2006

The effect of thalidomide on corticosteroid-dependent pulmonary sarcoidosis.

STUDY OBJECTIVE: To determine the benefit and corticosteroid-sparing potential of thalidomide in corticosteroid-dependent pulmonary sarcoidosis. METHODS: The study was a prospective open-label pilot study. Ten subjects were enrolled who had pulmonary sarcoidosis, required corticosteroid therapy for at least six months, and experienced a flare of pulmonary sarcoidosis within the previous 2 years when corticosteroids had been reduced or discontinued. Thalidomide was given at a dose of 200 mg/day for 24 weeks. Dose reductions were allowed in 50 mg/day increments for side effects. After 12 weeks, the baseline corticosteroid dose was halved for the remaining 12 weeks of the study. RESULTS: There were no clinically or statistically significant changes in spirometry (FVC% predicted: week 0: 72 +/- 4, week 12: 75 +/- 5, week 24: 73 +/- 4; p = NS), quality of life (as measured by the Short Form-36), or dyspnea (as measured by the Transitional Dyspnea Index) between weeks 0, 12, and 24. Three (30%) subjects demonstrated clinical evidence of a corticosteroid-sparing effect from thalidomide. Three (30%) subjects had to withdraw from the study; two at week 4 because of an acute pulmonary flare of sarcoidosis, and one because of possible side effects. Although nine of 10 (90%) of subjects required a reduction of the thalidomide dose because of side effects, no adverse effects were severe. The most common final dose of thalidomide was 100 mg/day. CONCLUSIONS: Thalidomide does not significantly improve pulmonary function or quality of life in patients with corticosteroid-dependent sarcoidosis. Few patients can tolerate doses of greater than 100 mg/day. Thalidomide may have been corticosteroid-sparing in a subgroup of these patients.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Chemotherapy dose intensity determination as a quality of care measure for managed care organizations in the treatment of early-stage breast cancer.

The objective of this study was to demonstrate how a clinical practice database can be used to illustrate the variations in adjunctive chemotherapy for breast cancer, to describe a measure of dose intensity (DI) to monitor that variation, and to design interventions to maximize a full-planned dose. An arbitrary sample of oncology practices across the United States was selected, each providing data on 10-20 patients treated with adjuvant chemotherapy for early-stage breast cancer. Data on 17,566 patients from 1,438 sites were collected, consisting of patient characteristics including age, number of positive nodes, planned and delivered chemotherapy agents, and a sample of absolute neutrophil or white blood cell counts by cycle. Mean age of the patient cohort was 48.5 years, and 54% of patients were below the age of 49. Treatment for the disease has changed during the 2 periods studied, 1983-1994 and 1995-1999. Use of Adriamycin/Cytoxan (AC) increased, whereas use of Cytoxan/Adriamycin/Fluorouracil (CAF) and full-dose Cytoxan/Methotrexate/Fluorouracil (CMF1) decreased. However, the less intense Cytoxan/Methotrexate/Fluorouracil combination (CMF2) has seen an actual increase in use during the 2 periods. Within the context of oncology care, including chemotherapy, full-dose intensive therapy and cure has always been the ultimate goal. In this study only 10% of the patients given AC received less than 85% of the full referenced dose, whereas about 20% of those receiving the other combinations fell into this category. Also, the summation dose intensity (SDI), a measure tying level of dose to survival, was highest in the AC group and lowest in the CMF2 group. Dose delays and dose reductions appear to account for the decrease in DI in the CMF1, CMF2, and CAF groups. DI, particularly SDI of adjuvant chemotherapy, which ties level of dose to survival in breast cancer patients, appears to be a reliable measure with which to assess the quality of care in community oncology practices. The 2 measures presented in this paper may be useful to managed care organizations for monitoring quality outcomes in this serious disease. Because one of the major reasons for reduction in chemotherapy dose appears to be neutropenia and its complications, these organizations can establish programs using DI as a basis for developing guidelines to optimize the clinical benefits of growth factors.

Adult↗
PubMed1999

Carcinoma in situ of the testis: review of biological and clinical features.

Carcinoma in situ of the testis (CIS) is the uniform precursor of testicular germ-cell tumours. Morphologically, CIS consists of large, intratubular, gonocyte-like cells with large nuclei and abundant glycogen. CIS cells are probably derived from primordial germ cells and are supposed to be present in the testis of a future testis cancer patient at the time of birth. CIS cells appear to spread inside the seminiferous tubules until CIS progresses to invasive cancer. Diagnosis is best achieved by surgical biopsy of the testis and subsequent immunohistological staining of placental alkaline phosphatase (PlAP). This enzyme is present in embryonal germ cells, CIS and seminoma as well as several other types of germ-cell tumour but usually not in normal germ cells. CIS is found in testicular tissue adjacent to testicular germ-cell tumours in about 90% of cases, and it is observed in all clinical groups known to be at risk for testicular cancer: cryptorchidism (2% to 4%), infertility (0% to 1%), ambiguous genitalia (25%) and contralateral testis of patients with testicular cancer (5%). Conversely, CIS is found in less than 1% of the normal male population, and this prevalence corresponds well to the life-time risk of testicular cancer in males. If CIS is left untreated, there is a 50% probability of progressing to frank germ-cell neoplasm within 5 years. Localised low-dose radiotherapy to the testis eradicates CIS and germ cells, while Leydig cells are preserved. The patient can thus be spared orchiectomy and hormone supplementation. Currently, dose-reduction studies are looking for the optimal radiation dose, which is expected to be around 14 to 16 Gy. After chemotherapy, there is a cumulative risk of 42% for recurrence of CIS within 10 years. The concept of CIS offers the chance of very early detection of testicular cancer and organ-preserving early treatment.

Carcinoma in Situ↗
PubMed1991

A phase I, II study of high-dose 5-fluorouracil and high-dose leucovorin with low-dose phosphonacetyl-L-aspartic acid in patients with advanced malignancies.

Twenty-eight patients with refractory advanced malignancies were treated with a 24-hour infusion of 5-fluorouracil (5-FU), leucovorin (LV), and N-(phosphonacetyl)-L-aspartic acid (PALA) weekly. Twenty-seven patients were evaluable to assess toxicity and antitumor activity. The PALA was administered as an intravenous bolus over 15 minutes at a fixed dose (250 mg/m2) 24 hours before the start of the 5-FU and leucovorin infusions. Initially the dose of 5-FU was 750 mg/m2; this was increased incrementally to 2600 mg/m2. The LV was administered in a fixed dose of 500 mg/m2 concurrently with the 5-FU over a 24-hour period. This regimen was repeated weekly. Diarrhea, stomatitis, nausea, and vomiting were among the dose-limiting toxicities. Others were hand-foot syndrome, hair loss of the scalp and eyelashes, overall weakness, rhinitis, and chemical conjunctivitis. The maximum tolerated dose of 5-FU in this combination and schedule was 2600 mg/m2. Seven of 14 patients treated with 2600 mg/m2 were able to tolerate the chemotherapy on a weekly basis without interruption. The other seven patients required dose reductions, but most received 5-FU at a dose of 2100 mg/m2. Twenty-three of 27 patients were treated previously. Eight patients had a partial response; five of these were treated previously. A complete response was observed in one patient with pancreatic carcinoma, previously untreated. The overall response rate for patients treated with 2100 or 2600 mg/m2 of 5-FU was nine of 18 patients (50%). Three of four previously untreated patients with pancreatic cancer responded to this treatment (two responded partially, and one had a complete response). One of three heavily pretreated patients with non-small cell lung cancer had a partial response as did a patient with breast cancer. Four of ten patients with colorectal cancer responded to the treatment (four partial responses), of whom three had been treated previously.

Adult↗
PubMed1987

Further experience with recombinant interferon alfa-2a with vinblastine in metastatic renal cell carcinoma: a progress report.

Thirty-three patients with measurable metastatic renal cell carcinoma were entered into 2 consecutive phase II protocols using interferon alfa-2a. In protocol I, 20 patients were treated with interferon alfa-2a at a dose of 36 X 10(6) IU i.m. t.i.w. Vinblastine was also given to 18 of these patients at a dose of 0.10-0.15 mg/kg i.v. every 2-3 weeks, depending on the blood cell count. In protocol 2, 13 patients received interferon alfa-2a at a dose of 18 X 10(6) i.m. t.i.w. with stepwise dose escalations of 3 X 10(6) IU being given every 2 weeks to 8 patients. Vinblastine, at a dose of 0.1 mg/kg every 3 weeks, was also given to 12 patients in protocol 2. Partial responses were seen in a total of 9 evaluable patients (lung, 5; lymph nodes, 2; liver, 1; and bone, 1), comprising 6 of 18 from protocol 1 and 3 of 13 from protocol 2. The median response duration was 89 days (range 91-540). No clinical parameter could be identified which was predictive for response. The subjective toxicity (flu-like symptoms and muscle pain) was considerable and necessitated dose reduction in 19 patients from protocol 1. The dose schedule of protocol 2 was tolerated better even after slight dose escalation. The considerable interpatient variation in toxicity, however, made any demonstration of a clear dose-toxicity relationship impossible. High dose interferon treatment of metastatic renal cell carcinoma combined with vinblastine results in a 33% response rate (95% confidence interval: 11-55%).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed2005

Neutropenia management with granulocyte colony-stimulating factors: from guidelines to nursing practice protocols.

Neutropenia, a problem that oncology nurses face in daily practice, is the major dose-limiting toxicity in patients with cancer who are treated with myelosuppressive chemotherapy. The incidence of chemotherapy dose reductions or treatment delays, which can impact overall dose intensity and compromise treatment outcomes, may be reduced by the proactive use of granulocyte colony-stimulating factor (G-CSF). National and international guidelines have been developed to promote the cost-effective use of G-CSF. Nursing care protocols for the management of chemotherapy-induced neutropenia (CIN) can be developed based on the national guidelines and modified for use by individual clinical practices. Risk assessment for CIN, which considers the prescribed chemotherapy regimen, patient risk factors, and treatment intent, should be a key component of the practice guidelines. Because most neutropenic events occur in the first cycle of chemotherapy, risk assessments should be conducted before the initiation of chemotherapy. Patients identified as at high risk for neutropenic complications should be given G-CSF in the first and subsequent cycles to allow the delivery of chemotherapy at full dose and on schedule. Nurses are instrumental in the development and implementation of neutropenia management protocols, which have the potential to markedly improve the quality of care and outcomes for patients with cancer.

Algorithms↗
PubMed2004

Thalidomide in patients with malignant pleural mesothelioma.

OBJECTIVES: The purpose of this study was to describe the experience with the anti-angiogenic agent thalidomide in the treatment of patients with a malignant pleural mesothelioma (MPM). MATERIALS AND METHODS: Patients with a histological confirmed diagnosis of malignant mesothelioma received thalidomide orally at night. Increasing doses of 100, 200 or maximally 400 mg were given till progression or unacceptable toxicity. Patients that did not show signs of progression for > or =6 months were considered responders. Neurological examination included the use a sensory nerve action potential (SNAP) test. RESULTS: Forty patients were evaluable for toxicity and efficacy. Twenty of them (50%) had received prior treatment. Thirty patients (75%) received a dose of 400 mg, 11 (37%) required dose reduction and 10 patients were confined to a dose of 200 mg or less. The major toxicity elicited by thalidomide concerned constipation (18/40 grade I and II) and two patients developed grade II neurotoxicity. A decline in SNAP test (>50%) did not seem to be related to the extent of neurological complaints. Eleven patients (27.5%) showed disease stabilization for >6 months and the median survival was 230 days (CI 130-330). CONCLUSIONS: The advised dose for future studies in these patients is 200 mg/day. At this dose level, the toxicity is mild and routine monitoring of neurological toxicity (SNAP test) can be omitted. The percentage of patients seen with prolonged disease stabilization upon thalidomide treatment warrants phase III studies in MPM.

Administration, Oral↗
PubMed2006

Phase I and pharmacologic study of sequential topotecan-carboplatin-etoposide in patients with extensive stage small cell lung cancer.

The inhibition of topoisomerase I by topotecan results in a compensatory increase in topoisomerase II associated with increased in vitro sensitivity of tumors to etoposide. Maximal synergy has been observed for the sequence of topotecan followed by etoposide. Carboplatin has clinical activity when combined with either of these two agents. These interactions were the pharmacologic rationale for topotecan p.o. days 1-5, carboplatin i.v. day 6, and etoposide p.o. days 6-10. Three successive dose levels were explored: (1) topotecan 2mg/day, carboplatin AUC 5, etoposide 150 mg/day; (2) topotecan 3mg/day, carboplatin AUC 5, etoposide 150 mg/day; and (3) topotecan 3mg/day, carboplatin AUC 5, etoposide 200mg/day. Filgrastim 5 microg/kg/day was injected s.c. days 11-18. Up to 6 cycles were administered every 21 days. Eligible patients had measurable or evaluable, extensive disease, small lung cell lung cancer, no prior chemotherapy, ECOG performance status 0-2, and adequate hematologic, renal, and hepatic function. Follow-up was weekly for CBC. Tumor response was assessed after 2 and 6 cycles. Dose limiting toxicity (DLT) was defined as any of the following in cycle 1: grade 3 or 4 non-hematologic toxicity other than nausea and vomiting, grade 4 neutropenia lasting more than 3 days, neutropenic fever or sepsis, grade 4 thrombocytopenia, or failure to recover neutrophils >or=1500/microl or platelets >or=100,000/microl by day 28. Ten patients were enrolled: median age 62 (range, 50-79); female/male 4/6; and performance status 0/1/2 in 2/7/1. Three patients each were treated on dose levels 1 and 2 without DLT. The first 2 patients entered on dose level 3 had no DLT. The third patient on dose level 3 developed grade 4 neutropenia lasting more than 3 days, neutropenic fever, and grade 4 thrombocytopenia on day 15 of cycle 1. The fourth patient on dose level 3 developed grade 4 thrombocytopenia on day 18 of cycle 1. One patient received only 1 cycle and was not evaluable for response. Seven patients completed 6 cycles: 1 had a complete response and 6 achieved a partial response. The third patient on dose level 3 received 2 cycles and had stable disease, but had to be removed from protocol treatment because of grade 4 neutropenia despite dose reduction in cycle 2. The fourth patient on dose level 3 achieved a partial response, but had to be removed from protocol therapy after cycle 5 because of recurrent grade 4 thrombocytopenia. In conclusion, neutropenia and thrombocytopenia were dose-limiting. The maximum tolerated dose (MTD) is topotecan 3mg/day p.o. days 1-5, carboplatin AUC 5i.v. day 6, and etoposide 150 mg/day p.o. days 6-10 with filgrastim.

Aged↗
PubMed2005

Follow-up of kidney graft recipients with cyclosporine-associated hemolytic-uremic syndrome and thrombotic microangiopathy.

The study was based on 462 patients who underwent kidney transplantation from 1986 through 2004. Cyclosporine (CsA)-related thrombotic microangiopathy (TMA) was observed in 15 (3.3%) patients. The donor ages ranged from 9 to 51 years and cold ischemia times from 12 to 31 hours. Hemolytic-uremic syndrome (HUS) developed 2 weeks after transplantation in 14 patients and later in 1 subject. Histopathologic examination demonstrated glomerular-type TMA in 3 patients, a mixed type (glomerular and vascular) in 11 patients, and a nonspecific mesangial widening with tubulointerstitial lesions in 1 patient. Follow-up biopsies revealed resolution of TMA in 4 patients and chronic vascular TMA in 1 patient. Six patients with mixed-type TMA needed transient hemodialysis. No patient with the glomerular-type TMA needed dialysis (P = .103), and 14 of 15 had good resolution of graft function after CsA dose reduction or temporary discontinuation or continuation of optimal dose. Only 1 graft with mixed-type TMA was lost due to irreversible HUS. The mean glomerular filtration rate (GFR), predicted by the Nankivell equation, was 76 +/- 13 mL/min and 80 +/- 27 mL/min at 1 month after discharge for glomerular- and mixed-type TMA, respectively (P > .05). GFRs 1 year after HUS were 82 +/- 12 and 87 +/- 21 mL/min for the glomerular and the mixed types, respectively (P > .05). We concluded that the mixed-type TMA was associated with a more severe early clinical course than the glomerular-type TMA. The 1-year prognosis was good in the majority of patients, with no significant differences between those with the glomerular- and mixed-type TMA.

Adolescent↗
PubMed1976

Studies in dose-time-volume relationships in bladder and tongue radium implants.

The clinical results of 26 tongue and 31 bladder radium implants were analysed in terms of proposed dose specification parameters that describe the dose-time-volume relationships of the implant. Tongue cases that recurred within two years were mostly those with a relatively short treatment time and in which a relatively large dose reduction factor had to be applied. The dose-time factor did not differ significantly in the groups of bladder implants having different clinical results. A higher incidence of necrosis was noted in bladder cases. This was associated with a significantly higher mean dose and a somewhat greater degree of dose inhomogeneity. Recurrences were generally linked with greater mean dose, target volume and dose inhomogeneity. These unfavourable dose-volume relationships were frequently associated with poor distribution of needles. The reported experimental and clinical findings pertinent to the differential sparing of normal tissues associated with protraction of continuous irradiation are outlined. In the light of these, it is felt that the results of tongue implants could have been improved by omission of the dose-time adjustment factor for treatment time of 3-10 days without undue risk of necrosis. However, bladder results could have been improved by attainment of a better implantation technique while keeping the treatment time within 6-8 days in view of the lower tolerance.

Carcinoma, Squamous Cell↗
PubMed1988

Pergolide: long-term use in Parkinson's disease.

Previous short-term studies have shown that the dopamine agonist pergolide improves control of Parkinson's disease when used in conjunction with carbidopa-levodopa (Sinemet). We assessed the long-term outcome (2 1/2- to 3-year follow-up) in patients with Parkinson's disease who participated in our previous pergolide double-blind trial and were subsequently switched to open-label pergolide therapy. Of 41 evaluable patients who began pergolide therapy, 10 (24%) experienced sustained substantial benefit that persisted to the end of this investigation. A total of 23 patients (56%) remained on pergolide therapy and, as a group, had considerable improvement over baseline at 2 1/2 to 3 years on the basis of several measurements of efficacy. A tendency toward deterioration could be reversed in many patients by larger or more frequent doses of carbidopa-levodopa; nevertheless, all but four patients were still taking the same dose or less of carbidopa-levodopa at the end of this study as at the onset. Patients with the best initial response to pergolide seemed most likely to experience long-term benefit. Confusion and hallucinations were the side effects most likely to necessitate discontinuation of pergolide. Symptoms suggestive of dose-related angina pectoris occurred in four patients in the open-label phase and two patients in the earlier double-blind phase (13% of patients who started pergolide therapy); these symptoms were easily controlled by dose reduction or discontinuation of pergolide, without sequelae. Dose-related leukopenia developed in one patient.

Aged↗
PubMed1998

The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced colorectal carcinoma: results of a phase III trial. Swiss Group for Clinical Cancer Research (SAKK).

PURPOSE: A wide variety of fluorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical use for the treatment of advanced colorectal cancer. Only the monthly low-dose LV-plus-FU regimen, as used by the North Central Cancer Treatment Group, has demonstrated a lasting survival benefit as opposed to FU alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this regimen for a confirmatory phase III trial but used the same dose-intensity of fluorouracil in both treatment arms. PATIENTS AND METHODS: Patients with inoperable or metastatic colorectal cancer were randomized to receive monthly FU 400 mg/m2/day plus LV 20 mg/m2/day as intravenous push daily for five days, or FU alone. RESULTS: Three hundred nine of the 310 patients randomized were eligible and included in the analysis. The objective response rate for patients with measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors for survival were performance status, weight loss, and disease symptoms. WHO > 2 toxicity, consisting of stomatitis (P = 0.001), diarrhea (P = 0.001), and nausea (P = 0.001), was more pronounced for FU-plus-LV, without fatal events. CONCLUSIONS: This is the largest published randomized trial to compare FU-plus-LV to FU alone in advanced colorectal cancer. It confirms the survival benefit obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU-plus-LV were acceptable to most patients, and they responded well to FU dose reductions. In the absence of an ideal dose-intense FU monotherapy regimen, monthly FU with low-dose LV provides a simple and economical means by which to achieve adequate FU efficacy in the treatment of advanced colorectal cancer.

Adult↗