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L Goedhals

Publications and source records attributed to L Goedhals.

At least 19 recordsLinked to original sources
PubMed2002

Phase II trial of pemetrexed disodium (ALIMTA, LY231514) in chemotherapy-naïve patients with advanced non-small-cell lung cancer.

BACKGROUND: To evaluate the efficacy and safety of pemetrexed therapy for chemotherapy-naïve patients with surgically incurable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients received pemetrexed 600 mg/m2 every 3 weeks. Restaging was performed after every two cycles of therapy and toxicity was assessed at each cycle of pemetrexed. In the absence of disease progression or undue toxicity, treatment was continued for a maximum of 12 cycles. RESULTS: Fifty-nine patients (median age 59 years; range 39-74 years) received a median of four cycles of pemetrexed. Nineteen patients (32%) had a ECOG performance status (PS) of two and 39 patients (66%) had stage IV disease. The most common histological sub-types were adenocarcinoma (20 patients, 34%) and large cell (18 patients, 31%). Sixteen patients (27%) had received prior radiotherapy. Nine patients achieved a partial response for an overall response rate of 15.8% (95% confidence interval CI 7% to 28%). The median duration of response was 4.9 months, and the median survival was 7.2 months. The principal toxicities were myelosuppression and rash. While grade 3 or 4 neutropenia was seen in 25 patients (42%), only two patients (3%) developed grade 3 infection. Eighteen patients (31%) developed grade 3 or 4 cutaneous toxicity, which improved with prophylactic oral dexamethasone administered for 3 days beginning the day before pemetrexed treatment. Asymptomatic elevations in hepatic biochemistry (especially alanine transaminase and aspartate transaminase) were seen in 47 patients (80%); however, these did not interfere with the dose or schedule of pemetrexed and returned to normal levels throughout the study. CONCLUSIONS: This is the largest study confirming the encouraging single-agent activity of pemetrexed in chemotherapy-naïve patients with NSCLC. In addition, this study demonstrates that a dose of 600 mg/m2 can be delivered safely; however, treatment should be restricted to patients with a PS of 0 or 1. The results of combination studies are awaited with interest.

Adult↗
PubMed2001

Comparison of the Batho, ETAR and Monte Carlo dose calculation methods in CT based patient models.

This paper shows the contribution that Monte Carlo methods make in regard to dose distribution calculations in CT based patient models and the role it plays as a gold standard to evaluate other dose calculation algorithms. The EGS4 based BEAM code was used to construct a generic 8 MV accelerator to obtain a series of x-ray field sources. These were used in the EGS4 based DOSXYZ code to generate beam data in a mathematical water phantom to set up a beam model in a commercial treatment planning system (TPS), CADPLAN V.2.7.9. Dose distributions were calculated with the Batho and ETAR inhomogeneity correction algorithms in head/sinus, lung, and prostate patient models for 2 x 2, 5 x 5, and 10 X 10 cm2 open x-ray beams. Corresponding dose distributions were calculated with DOSXYZ that were used as a benchmark. The dose comparisons are expressed in terms of 2D isodose distributions, percentage depth dose data, and dose difference volume histograms (DDVH's). Results indicated that the Batho and ETAR methods contained inaccuracies of 20%-70% in the maxillary sinus region in the head model. Large lung inhomogeneities irradiated with small fields gave rise to absorbed dose deviations of 10%-20%. It is shown for a 10 x 10 cm2 field that DOSXYZ models lateral scatter in lung that is not present in the Batho and ETAR methods. The ETAR and Batho methods are accurate within 3% in a prostate model. We showed how the performance of these inhomogeneity correction methods can be understood in realistic patient models using validated Monte Carlo codes such as BEAM and DOSXYZ.

Algorithms↗
PubMed1999

Efficacy of an ondansetron orally disintegrating tablet: a novel oral formulation of this 5-HT(3) receptor antagonist in the treatment of fractionated radiotherapy-induced nausea and emesis. Emesis Study Group for the Ondansetron Orally Disintegrating Tablet in Radiotherapy Treatment.

A significant number of patients who are receiving radiotherapy experience the distressing side effects of emesis and nausea. Although prophylactic antiemetics are often given to patients who are receiving single-fraction, high-dose radiotherapy to the abdomen, a survey has revealed that antiemetic prophylaxis is not routinely offered to those receiving fractionated radiotherapy. Hence there is a need for an effective treatment of emesis for use in this group of patients. Ondansetron is an effective and well-tolerated antiemetic, which is used for the prevention of both chemotherapy and radiotherapy-induced emesis and nausea. This agent has been developed as a novel freeze-dried oral formulation. Ondansetron orally disintegrating tablets (ondODT) disperse rapidly when placed on the tongue. As the tablet does not need to be swallowed with water, it is a particularly useful formulation for patients who have difficulty with swallowing or who do not feel able to drink. This study was undertaken to investigate the efficacy of ondODT in the treatment of established emesis and nausea induced by radiotherapy. Two doses of ondODT, 8 mg and 16 mg, were compared with placebo in patients who developed emesis and/or moderate/severe nausea after receiving fractionated radiotherapy to sites located between the thorax and the pelvis. The study showed that ondODT was clinically superior to placebo in treating emesis and nausea successfully over a 12-hour period after taking the medication. There were no statistically significant differences between the two doses of ondODT. In the 2 hours after taking the study medication, patients who received ondODT (8 mg and 16 mg) had significantly fewer emetic episodes compared with those who received placebo. They also experienced significantly less nausea. In conclusion, ondODT 8 mg is effective in the treatment of radiotherapy-induced emesis and nausea and provides an effective alternative to the conventional ondansetron tablet.

Administration, Oral↗
PubMed1999

Phase II trial of i.v. vinorelbine and cisplatin in inoperable locally advanced or disseminated non-small-cell lung cancer: the South African experience.

PURPOSE: This multicentre phase II trial was conducted in South Africa to evaluate the activity of a combination of vinorelbine, administered in a new schedule, and cisplatin, in chemonaive patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between September 1995 and December 1996, 35 patients were enrolled. All patients had at least one bidimensionally measurable lesion. Vinorelbine was administered intravenously on day 1 and day 8 at a dose of 30 mg/m2 and cisplatin was administered intravenously on day 1 at a dose of 100 mg/m2. The chemotherapy cycle was repeated every three weeks. RESULTS: Of 35 evaluable patients, 14 (40%) achieved a response (one complete response and 13 partial responses). The median time to progression was 6.4 months (range 12-572 days) and the median survival was 15.7 months (range 12-882+ days). One-year survival was 56%. Toxicity was manageable and consisted of nausea and vomiting (grade 3 in 45% of patients) and grade 3-4 neutropenia seen in 13 patients with three patients experiencing grade 3 infection. Other side-effects were mild, including constipation grade 3 in 9.1%. A total of 153 courses were administered with patients receiving a median dose intensity of 81.7% for vinorelbine, while that of cisplatin was 74.1%. CONCLUSION: The combination of vinorelbine and cisplatin demonstrated substantial activity in terms of objective response and survival with manageable side-effects in patients with advanced NSCLC. These findings confirm the data from previous randomised studies. Further studies are ongoing in order to evaluate the efficacy of this combination in the neoadjuvant and adjuvant setting.

Adult↗
PubMed1998

Control of delayed nausea and vomiting with granisetron plus dexamethasone or dexamethasone alone in patients receiving highly emetogenic chemotherapy: a double-blind, placebo-controlled, comparative study.

BACKGROUND: The efficacies of granisetron plus dexamethasone and dexamethasone alone in controlling delayed nausea and vomiting after cisplatin chemotherapy (> or = 69 mg/m2) were compared in a multicentre, double-blind, placebo-controlled comparative study. PATIENTS AND METHODS: In all, 654 patients (of whom 619 were evaluable) received prophylactic granisetron plus dexamethasone before chemotherapy on day 0; on day 1 complete responders and non-responders were randomized separately to receive dexamethasone, 8 mg b.d. p.o., with either granisetron, 1 mg b.d. p.o., or matching placebo for six days. RESULTS: Over days 1-6 the complete response rates were 54.5% (dexamethasone group) and 52.1% (dexamethasone plus granisetron group). Response rates were higher over days 4-6 (71.8% and 70.7%, respectively) than over days 1-3 (60.4% and 57.9%, respectively). Significantly more patients who responded to antiemetic treatment during day 0 were responders over days 1-6 (63% vs. 17%; P < 0.001). No other treatment-related differences were found. Adverse events tended to be minor, with constipation and headache the most common. Overall, there were no significant differences in the safety profiles of the two regimens, but constipation and abdominal pain were significantly more common in the dexamethasone plus granisetron group. CONCLUSIONS: Granisetron plus dexamethasone did not appear to confer additional benefit over use of dexamethasone alone in controlling delayed nausea and vomiting following cisplatin chemotherapy. Control of acute nausea and vomiting, however, appeared to be an important factor influencing delayed nausea and vomiting.

Adult↗
PubMed1998

A multicenter, double-blind comparison of i.v. and oral administration of ondansetron plus dexamethasone for acute cisplatin-induced emesis. Ondansetron Acute Emesis Study Group.

A total of 530 patients were treated in this multicenter, double-blind, double-dummy, parallel group study to compare the anti-emetic efficacy and safety of a once daily ondansetron oral regimen with a once daily i.v. dosing regimen over a 24 h period, administered to patients prior to receiving cisplatin (50 mg/m2 or greater) chemotherapy. Patients were randomized to receive a single dose of ondansetron plus dexamethasone given either orally (ondansetron 24 mg and dexamethasone 12 mg, n=262) or i.v. (ondansetron 8 mg and dexamethasone 20 mg, n=268). Complete control of emesis (i.e. no emetic episodes, no rescue and no premature withdrawal) was achieved for 85% of patients (224 of 262) in the oral group and 83% (223 of 268) in the i.v. group. No nausea was reported in 70% of patients in the oral group and 68% in the i.v. group. There were no statistically significant differences between the two groups for any of the assessments of efficacy, which included time to first emetic episode, number of emetic episodes and the worst grade of nausea occurring over the 24 h study period. Once daily ondansetron oral and i.v., in combination with dexamethasone, was well tolerated in this study. In conclusion, once daily oral ondansetron 24 mg plus dexamethasone is equally effective in the control of emesis and nausea induced by highly emetogenic chemotherapy as once daily ondansetron 8 mg i.v. plus dexamethasone.

Administration, Oral↗
PubMed1998

The indirect use of CT numbers to establish material properties needed for Monte Carlo calculation of dose distributions in patients.

A number of Monte Carlo codes are available, which can be used to calculate dose distributions n patients with high accuracy. Patient geometry can readily be derived with adequate spatial resolution from CT scans. To perform the Monte Carlo calculation with the same spatial resolution, it is necessary to enter the atomic composition and density of the tissue in each voxel of the CT image. This means entering 65,536 discrete values for a CT slice with a 256 x 256 matrix size. The need for automated methods of setting up the material data files is obvious. Because there is no direct unique relationship between CT numbers and material composition, the aim of our work was to devise a method whereby the atomic composition and density in each voxel could be assigned automatically by indirect derivation from the CT numbers. The set of all tissues types in the human body was divided into subsets that are dosimetrically equivalent, based on Monte Carlo calculated depth dose curves in homogeneous phantoms of each tissue. CT number ranges corresponding to each tissue subset were determined from the calibration curve linking electron density with CT number for the specific CT scanner. Further subdivision was found to be necessary for the lung and bone type tissues. This was done by keeping the atomic composition constant and varying the physical density. It was found that 57 distinct tissue subsets were needed to represent the 16 main tissue types in the body at a 1% dose level. Corresponding CT number intervals of 30 HU were needed in the lung and soft tissue region, whereas in the bone region the intervals could be increased to 100 HU. A computer algorithm was set up to convert automatically from CT number to corresponding equivalent material number for the Monte Carlo preprocessor code.

Algorithms↗
PubMed1997

Radiation dose estimates of 186Re-hydroxyethylidene diphosphonate for palliation of metastatic osseous lesions: an animal model study.

A common complication in patients with breast or prostate cancer is bone metastases causing pain. New radionuclide therapy methods have recently been proposed for palliation, including 186Re-hydroxyethylidene diphosphonate (186Re-HEDP). This paper reports on the local development of 186Re-HEDP and the biodistribution studied in animals for eventual use in patients. Adult dose was computed assuming a 70 kg standard man. The 186Re was labelled to HEDP using standard techniques. The biodistribution in five Chacma baboons (Papio ursinus) was studied. Doses ranging from 39.4 to 44.9 MBq kg(-1) (mean 43.6 +/- 2.8 MBq kg[-1]) were administered, corresponding to an adult human dose of 2960 MBq (80 mCi). Whole-body images of the animals were obtained with a dual-headed scintillation camera on an hourly basis for 6 h post-injection and then daily for 3 days. The bone, soft tissue, kidneys and urinary bladder were considered source organs and data from these organs were used in a compartmental model to obtain the mean residence times of the radionuclide in the different source organs. Radiation dose estimates for 186Re-HEDP were subsequently obtained with the MIRDOSE 3 program. The estimated absorbed radiation doses to some of the organs (expressed in mGy MBq[-l]) were as follows: bone surface 1.69; kidneys 0.09; liver 0.04; ovaries 0.04; red marrow 0.75; total body 0.12; urinary bladder wall 0.43. 186Re-HEDP yielded an effective dose of 0.17 mSv MBq(-1). The radiation dose delivered to the bone marrow in this study did not cause any detrimental effect to the baboons, indicating that locally produced 186Re-HEDP is suitable for clinical use.

Adult↗
PubMed1997

Weekly gemcitabine with monthly cisplatin: effective chemotherapy for advanced non-small-cell lung cancer.

PURPOSE: The aim of this study was to examine the efficacy of a regimen of initial gemcitabine followed by cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-three patients (36 men and 17 women; age range, 35 to 74 years) were enrolled. Patients had bidimensionally measurable disease. Gemcitabine (phase-specific agent) was administered on days 1, 8, and 15 at a dose of 1,000 mg/m2. Cisplatin (cycle-specific agent) was administered on day 15 (100 mg/m2). Chemotherapy was administered in 28-day cycles. RESULTS: Of 53 patients enrolled, 50 were assessable for response. The overall response rate was 52%. There were two complete responses (4%) and 24 partial responses (48%). The median survival duration was 13 months and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization (WHO) grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia occurred in 13.3% and 7.7% of patients, respectively. Most patients experienced mild nausea and vomiting. Few patients had hair loss and oral toxicity was mild. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. For the first two cycles of chemotherapy, the dose-intensity per infusion was 947 mg/m2 for gemcitabine and 85 mg/m2 for cisplatin. CONCLUSION: This regimen of gemcitabine and cisplatin was effective, with high response and survival rates and few dosage modifications during its administration. Prospective randomized studies with other cisplatin-based combination chemotherapy regimens are indicated.

Adult↗
PubMed1997

Weekly gemcitabine and monthly cisplatin for advanced non-small cell lung carcinoma.

Most chemotherapy for non-small cell lung cancer (NSCLC) currently includes combination chemotherapy based on cisplatin. Gemcitabine is a nucleoside analog with demonstrated activity against NSCLC, yet it has low toxicity. This phase II study was designed to examine the efficacy of a combination chemotherapy regimen consisting of gemcitabine followed by cisplatin. The patient population comprised 53 patients with pathologically confirmed locally advanced or metastatic NSCLC. Gemcitabine 1,000 mg/m2 was administered on days 1, 8, and 15 and cisplatin 100 mg/m2 was given on day 15. Chemotherapy was administered every 28 days. Of the 50 patients evaluable for response, there were two complete responses (4%) and 24 partial responses (48%). The median duration of response was 8.5 months, median survival was 13 months, and the 1-year survival rate was 61%. The regimen was generally well tolerated. World Health Organization grade 3 leukopenia occurred in 28.8% of patients, while grade 3 and 4 neutropenia occurred in 38.8% and 19.2% of patients, respectively. Grade 3 and 4 thrombocytopenia was seen in 13.3% and 7.7% of patients, and grade 3 and 4 anemia occurred in 11.5% and 1.9% of patients, respectively. Alopecia and oral toxicity was mild, although most patients experienced mild nausea and vomiting. Relatively few patients required dose modifications for any of the three weekly doses of chemotherapy. We conclude that the combination of gemcitabine and cisplatin is an effective regimen for NSCLC, resulting in high response and survival rates. Additional prospective randomized studies with other cisplatin-based combination chemotherapy regimens are warranted.

Adult↗
PubMed1996

A multicentre, double-blind study comparing placebo, ondansetron and ondansetron plus dexamethasone for the control of cisplatin-induced delayed emesis. Ondansetron Delayed Emesis Study Group.

BACKGROUND: The purpose of this study was to investigate the efficacy and safety of oral ondansetron, given alone or in combination with dexamethasone in the control of cisplatin-induced delayed emesis. PATIENTS AND METHODS: This was an international, multicentre, double-blind, randomised, placebo-controlled, parallel group study. A total of 640 chemotherapy-naïve patients received ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. for the control of acute emesis prior to cisplatin (> or = 70 mg/m2) on day 1. Patients who were not rescued or withdrawn on day 1 were to be randomised 24 hours after the start of cisplatin administration to one of four groups; group I placebo oral (p.o.), twice daily (bd) on days 2-6 (n = 125); group II ondansetron (8 mg p.o. bd) on days 2/3 followed by placebo (p.o. bd) on days 4-6 (n = 199); group III ondansetron (8 mg p.o. bd) on days 2-6 (n = 214); group IV ondansetron (8 mg p.o. bd) plus dexamethasone (4 mg p.o. bd) on days 2-6 (n = 66). RESULTS: On day 1, 81% of patients had complete control of acute emesis, with 68% having no emesis and no nausea. Over days 2/3 and over days 2-6, significantly more patients receiving ondansetron plus dexamethasone (group IV) reported no emesis and no nausea (49% and 45%, respectively) compared to ondansetron alone (32% and 27%, respectively) or placebo (group I; 33% and 27%, respectively; P < 0.05 for all pairwise comparisons). There were no significant differences in the control of emesis over days 2/3, where 61% of patients had complete emetic control (0 emetic episodes) with ondansetron plus dexamethasone (group IV), 54% with ondansetron (groups II + III) and 49% with placebo (group I). In the distribution of nausea grades, ondansetron plus dexamethasone (group IV) was significantly superior to ondansetron (groups II + III); P = 0.037) and placebo (group I; P = 0.013) over days 2/3. Over days 2-6 there were no significant differences in the control of emesis, however a comparison of the distribution of nausea grades over days 2-6 showed ondansetron plus dexamethasone (group IV) to be significantly superior to ondansetron (group III; P = 0.043) and placebo (group I; P = 0.024). All treatments were well tolerated and no unexpected drug-related adverse events were reported. There were no differences in the overall incidence of adverse events between the active treatment groups or placebo. Constipation and headache, recognised side effects of 5-HT3 receptor antagonists, were the most commonly reported adverse events with the incidence of constipation with ondansetron alone (group III) being significantly greater than with over days 2-6 (14% vs. 6%; P = 0.030). CONCLUSION: In contrast to some previous investigations, in this study, ondansetron alone appears to have a minor role in the control of cisplatin-induced delayed emesis and nausea. In conclusion, the combination of oral ondansetron plus dexamethasone is superior to ondansetron and to placebo.

Adult↗
PubMed1995

Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer.

PURPOSE: To perform a randomized three-arm comparison of tamoxifen (TAM; 20 mg/d) and two separate doses of toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d [TOR200]) in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer. MATERIALS AND METHODS: Six hundred forty-eight patients with hormone receptor-positive or -unknown metastatic breast cancer were randomly assigned to receive TAM (n = 215), TOR60 (n = 221), or TOR200 (n = 212). RESULTS: The combined response rates (by intent to treat) were as follows;: TAM, 44%; TOR60, 50%; and TOR200, 48%. Complete and partial response rates were as follows: TAM, 19%; TOR60, 21%, and TOR200, 23% (not statistically different). Median times to progression and overall survival were not significantly different. Adverse events (lethal, serious but nonlethal, and important but non-life-threatening) were similar in all three arms, except that patients in the TOR200 arm had a statistically significantly increased rate of nausea (37% v 26% and 26% for TOR200, TAM, and TOR60, respectively; P = .027). Quality-of-life assessments were not different among the three arms. CONCLUSION: The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM. We detected no clear evidence of a dose-response effect for TOR. TOR60 is an effective and safe agent for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer and can be considered an alternative to TAM as first-line treatment for such patients.

Adult↗
PubMed1995

Technical note: computed tomography imaging with a radiotherapy simulator.

An inexpensive system for obtaining cross-sectional information and accurate body outlines of patients destined for radiotherapy, using a radiotherapy simulator without any major modifications, has been investigated. The image intensifier of the simulator was moved laterally and a narrow fan beam of X-rays passed through the phantom onto the intensifier. Several television (TV) lines of the video signal from the TV camera were digitized by a frame grabber and stored for reconstruction. Multiple projections were acquired by rotating the gantry of the simulator. The field of view was enlarged by increasing the offset distance of the image intensifier and taking two sets of projections. Reconstruction was carried out by using the convolution and back-projection method. The gradient between pixel values in the reconstructed images was used to detect the outlines of structures in the images. The accuracy of outline detection was evaluated with images of a Rando phantom. The outlines of the images were compared with the actual outlines of the phantom. The spatial resolution of the simulator computed tomography (CT) was measured to be 4.05 mm. Large inhomogeneities could be clearly seen. The average difference between the measured and the actual outlines was 3.0 mm with a maximum difference of 10.0 mm at sharp curves in the outline. The simulator CT provides an inexpensive, alternative method of obtaining body outlines and does not require any modifications to the simulator. Data acquisition, processing and display can be performed on a personal computer with image processing facilities.

Head↗
PubMed1995

Bioavailability and pharmacokinetic characteristics of dexniguldipine-HCl, a new anticancer drug.

Dexniguldipine-HCl is a new dihydropyridine derivative with antineoplastic activity and potency for overcoming multidrug resistance. In this pharmacokinetic study the bioavailability of 3 doses of an oral formulation of dexniguldipine was to be determined. Fourteen patients with malignant disease not eligible for higher priority treatment and sufficient general condition were included. In 12 patients all pharmacokinetic investigations were available for evaluation. A single 4-h infusion of 2 mg per kg body weight of dexniguldipine was given as reference. Thereafter 3 increasing oral dosages (750, 1,500, 2,250 mg/d) were given on a 3-time daily basis for 3 consecutive weeks. On day 7 (under steady state conditions) of each period, a pharmacokinetic profile was done. Absolute bioavailability at the 3-dose levels was 3, 4, and 5%, respectively, thus slightly increasing with dose, but generally low. After intravenous administration terminal half life was 22.4 h, clearance 36.9 l/h and volume of distribution 1,193 1. Toxicity was tolerable with main adverse events being loss of appetite, nausea, and vomiting. Cardiovascular effects and a decrease in serum calcium were reported in several patients. Patients were allowed to continue treatment if a benefit was expected, and 2 patients showed tumor regression during treatment. One patient with renal cell carcinoma achieved a partial remission. Bioavailability of this oral formulation seems too low for routine clinical use, despite the fact that clinical effects have been observed.

Administration, Oral↗