Comments on economic evaluation of chemotherapy.
Explore the source record for details and available documents.
Antineoplastic Agents↗
Biomedical subjects
H Mouridsen
Publications and source records attributed to H Mouridsen.
[Medical treatment of cancer].
Explore the source record for details and available documents.
Antineoplastic Agents↗
Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
PURPOSE: The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas. PATIENTS AND METHODS: This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C). RESULTS: The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar. CONCLUSION: In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.
Antineoplastic Combined Chemotherapy Protocols↗
Phase II study of liposomal muramyl tripeptide phosphatidylethanolamine (MTP/PE) in advanced soft tissue sarcomas of the adult. An EORTC Soft Tissue and Bone Sarcoma Group study.
The EORTC Soft Tissue and Bone Sarcoma Group conducted a phase II study with intravenous muramyl tripeptide phosphatidylethanolamine (MTP/PE) at a dose of 4 mg once weekly in 20 patients with metastatic soft tissue sarcomas. Responses were not seen in 19 evaluable patients. Toxicity consisted mainly of a mild flu-like syndrome after 62% of drug administrations. It is concluded that MTP/PE at this dose and schedule has no activity in metastatic soft tissue sarcoma.
Acetylmuramyl-Alanyl-Isoglutamine↗
Breast cancer screening: methods, human benefits, human costs.
Explore the source record for details and available documents.
Adult↗
Effect of high-dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial.
We performed a randomised single blind trial of high-dose dexamethasone as an adjunct to radiotherapy in patients with metastatic spinal cord compression from solid tumours. After stratification for primary tumour and gait function, 57 patients were allocated randomly to treatment with either high-dose dexamethasone or no steroidal treatment. Dexamethasone was administered as a bolus of 96 mg intravenously, followed by 96 mg orally for 3 days and then tapered in 10 days. A successful treatment result defined as gait function after treatment was obtained in 81% of the patients treated with dexamethasone compared to 63% of the patients receiving no dexamethasone therapy. Six months after treatment, 59% of the patients in the dexamethasone group were still ambulatory compared to 33% in the no dexamethasone group. Life table analysis of patients surviving with gait function showed a significantly better course in patients treated with dexamethasone (P < 0.05). Median survival was identical in the two treatment groups. Similar results were found in subgroup analysis of 34 patients with breast cancer as the primary malignancy. Significant side-effects were reported in 3 (11%) of the patients receiving glucocorticoids, 2 of whom discontinued the treatment. We conclude that high-dose glucocorticoid therapy should be given as adjunct treatment in patients with metastatic epidural spinal cord compression.
Adult↗
Regional trends in breast cancer incidence and mortality in Denmark prior to mammographic screening.
To provide a basis for the evaluation of mammographic screening programmes in Denmark, a study was undertaken of the regional differences in breast cancer incidence and mortality. All 16 regions were followed for the 20 year period, 1970-89, before the start of the first population-based mammographic screening programme in the Copenhagen municipality in 1991. Multiplicative Poisson models were used for the analysis. In general, the incidence increased during this period from 55 to 70 [per 100,000 standardised world standard population (WSP)], and the analysis shows this to be most pronounced among women below age 60. The mortality was more stable, changing only from 24 to 28 (per 100,000 standardised WSP), but a significant increase occurred in the late 1980s. The study showed regional differences in both incidence and mortality of breast cancer in Denmark. Both the incidence and the mortality varied between the regions, with maximum differences of 22%. The analysis showed no variation in the time trends in the different regions, and thus indicates that the use of a regional comparison group would be a valid basis for evaluation of the Copenhagen programme. Our study, however, underlies the difficulties inherent in the evaluation of screening programmes without internal control groups.
Adolescent↗
Vimentin expression in 98 breast cancers with medullary features and its prognostic significance.
The expression of vimentin, as assessed by immunohistochemistry, has been evaluated in 69 medullary carcinomas of the breast: 28 typical medullary carcinomas (TMC), 41 atypical medullary carcinomas (AMC), and 29 invasive ductal carcinomas with subtle medullary features that, however, did not fulfill the strict criteria of TMC or AMC. Immunoreactivity of at least 10% of the component cells was found in 14 of the medullary carcinomas (5 out of 28 TMC, 9 out of 41 AMC whereas only 1 of the invasive ductal carcinomas was vimentin-positive. The patients were followed for 8-13 years. No difference in recurrence-free survival or overall survival could be documented between vimentin-positive and vimentin-negative carcinomas with medullary features. No biological significance could be established for vimentin labelling in these lesions.
Breast Neoplasms↗
Phase II study of miltefosine (hexadecylphosphocholine) in advanced soft tissue sarcomas of the adult--an EORTC Soft Tissue and Bone Sarcoma Group Study.
The EORTC Soft Tissue and Bone Sarcoma Group conducted a phase II study with oral miltefosine at a dose of 50 mg thrice daily in patients with metastatic soft tissue sarcomas. No responses were seen in 18 evaluable patients. Toxicity consisted mainly of nausea/vomiting. It is concluded that oral miltefosine has no activity in soft tissue sarcoma.
Administration, Oral↗
Selection of large and objectively measurable target lesions in EORTC phase II trials: impact on recruitment and response rate. EORTC Soft Tissue and Bone Sarcoma Group (STBSG).
The EORTC has recently issued minimum requirements for target lesions in phase II trials, aiming at a decrease in measurement errors [minimum size, computer tomography (CT) scan or ultrasound for deep lesions]. Their impact on recruitment and response has been retrospectively studied in a trial of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), investigating high-dose chemotherapy in patients with advanced soft tissue sarcoma, where 46/103 objective responses were seen, including 10 complete responses. For the 20 patients who did not satisfy the criteria, a similar objective response rate and a significantly higher complete response rate were reported. Among 265 target lesions, the same trends were observed when comparing small to large lesions, for different tumour sites. For deep lesions clinically assessed, significantly higher response rates were reported than for those measured by CT scans or ultrasound. The new stricter EORTC criteria improve the reliability of measurements and have been adopted for future phase II trials of the STBSG. This will not result in the selection of potentially poor responders. Less than 20% of the present recruitment will be lost.
Antineoplastic Combined Chemotherapy Protocols↗
Prednisolone in the treatment of severe malignant hypercalcaemia in metastatic breast cancer: a randomized study.
To determine the effect of prednisolone on severe hypercalcaemia in women with metastatic breast cancer, 30 patients with serum ionized calcium above 1.60 mmol l-1 (reference range 1.15-1.35 mmol l-1) entered a randomized trial. Performance status before entry to the trial and survival time after hypercalcaemia were also noted. All patients received 4 l of isotonic saline daily and 80 mg intravenous furosemide three times daily for 2 d; thereafter they received 3 l of isotonic saline daily and 80 mg furosemide twice daily for 6 d. Fifteen patients were randomized to receive prednisolone, 25 mg orally, three times daily for 8 d. Serum ionized calcium decreased significantly in both groups, but most markedly in the prednisolone group. The median difference was 0.28 mmol l-1 (95% confidence interval (CI), 0.09-0.52) on day 4 and 0.21 mmol l-1 (95% CI, 0.12-0.44) on day 8. In seven prednisolone-treated patients serum ionized calcium normalized, compared to none in the control group (Fisher's exact test; P = 0.028). No severe adverse effects were observed. Prior to detection of hypercalcaemia all patients were severely immobilized, primarily due to bone pain. Only 10 patients were still living after 3 months. Prednisolone, furosemide and rehydration is superior to furosemide and rehydration alone in severely hypercalcaemic patients with metastatic breast cancer in whom immobilization appears to be an early warning sign of life-threatening hypercalcaemia. The short survival time was not influenced by prednisolone.
Administration, Oral↗
Acute monocytic or myelomonocytic leukemia with balanced chromosome translocations to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer.
PURPOSE: To report five cases of acute monocytic or myelomonocytic leukemia after chemotherapy with 4-epidoxorubicin for breast cancer and to evaluate the risk of leukemia after the use of this drug. PATIENTS AND METHODS: One hundred fifty-seven patients with advanced breast cancer were randomized to either 4-epi-doxorubicin plus cisplatin or 4-epi-doxorubicin alone. An additional 203 patients were treated prospectively with 4-epi-doxorubicin alone. All were observed closely for leukemic complications. RESULTS: Three patients from the randomized study developed leukemia; all were in the subgroup of 74 patients who received 4-epi-doxorubicin plus cisplatin, whereas no leukemia was observed among the remaining 83 patients in the randomized study or among the additional 203 patients who were treated prospectively with 4-epi-doxorubicin alone (P = .023, log-rank test). In the subgroup of 74 patients who were treated with 4-epi-doxorubicin plus cisplatin, the cumulative risk of leukemia was 16.0% +/- 9.9% (mean +/- SE) 33 months after the start of therapy; the relative risk was 668 (95% confidence interval [Cl], 138 to 1,953). Two other cases of acute monocytic and myelomonocytic leukemia were observed after 4-epi-doxorubicin plus alkylating agents were administered for breast cancer. Three of five cases of leukemia presented balanced translocations to chromosome band 11q23 and two, loss of a whole chromosome no. 7 or its long arm. CONCLUSIONS: 4-epi-doxorubicin is leukemogenic, and the leukemias are often acute monocytic or myelomonocytic with balanced chromosome translocations to band 11q23, such as in the leukemias after therapy with the epipodophyllotoxins. Furthermore, our results suggest a synergistic effect in leukemogenesis between 4-epi-doxorubicin targeting DNA-topoisomerase II and directly genotoxic drugs such as cisplatin or alkylating agents.
Antineoplastic Combined Chemotherapy Protocols↗
Experience with ifosfamide in the EORTC Soft Tissue and Bone Sarcoma Group.
The Soft Tissue and Bone Sarcoma Group of the European Organization on Research and Treatment of Cancer has conducted a number of studies of chemotherapy in advanced disease over the past 15 years. Following the discovery that the CYVADIC regimen (cyclophosphamide/vincristine/doxorubicin/dimethyl imidazole carboxamide) was less active than had been reported originally, the individual components of CYVADIC were studied. This showed that doxorubicin had considerable activity and that ifosfamide 5 g/m2 given over 24 hours was at least as active as cyclophosphamide. Subsequent studies have therefore centered on a combination of doxorubicin and ifosfamide. A large randomized trial showed no significant benefit of doxorubicin/ifosfamide over single-agent doxorubicin, but the doses of doxorubicin were different. More recently, using bone marrow growth factors, it has been possible to increase the doxorubicin dose to that given as a single agent and also maintain the ifosfamide dose. This is now being tested in a randomized trial to determine whether improved response rates and other indicators of outcome will be seen.
Antineoplastic Combined Chemotherapy Protocols↗
A pharmacokinetic study of prednimustine as compared with prednisolone plus chlorambucil in cancer patients.
The pharmacokinetic characteristics of prednisolone and of chlorambucil and its beta-oxidized metabolite, phenylacetic mustard (PAM) were studied in plasma after the oral administration of 200 mg prednimustine (Sterecyt) and a regimen consisting of 20 mg prednisolone plus 20 mg chlorambucil, respectively. A total of 12 cancer patients completed this trial. The drugs were given in a cross-over study as single doses, and serial plasma samples were collected for 32 h. Chlorambucil and PAM were assayed by a gas chromatographic/mass spectrometry method and prednisolone, by radioimmunoassay. The median relative availability of the prednisolone and chlorambucil moiety in prednimustine was 19% and 16%, respectively. Prednisolone, as well as chlorambucil and PAM, appeared later and at a significantly lower concentration in plasma after treatment with prednimustine as compared with the mixture of chlorambucil and prednisolone. We also found that the elimination phase of chlorambucil and PAM in plasma is prolonged after the administration of prednimustine as compared with chlorambucil per se. In contrast, the elimination of the prednisolone moiety of prednimustine and that following the administration of a plain prednisolone tablet did not seem to differ. The modified plasma profile of the alkylating components following prednimustine administration may be important for the clinical efficacy of prednimustine.
Adult↗
Doxorubicin in relapsed soft tissue sarcoma: justification of phase II evaluation of new drugs in this disease. An EORTC Soft Tissue and Bone Sarcoma Group Study.
Explore the source record for details and available documents.
Adult↗
Adjuvant chemotherapy with doxorubicin in high-grade soft tissue sarcoma: a randomized trial of the Scandinavian Sarcoma Group.
From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.
Adolescent↗
[Medical treatment of cancer--an elucidating report].
Explore the source record for details and available documents.
Antineoplastic Agents↗
Review of the clinical trials activity of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer.
Despite the low incidence of sarcomas, the Soft Tissue and Bone Sarcoma Group has established itself as one of the more active cooperative groups of the European Organization for Research and Treatment of Cancer. Performing over a 10 yr period three phase III protocols (total entry 750 patients), three randomized phase II studies (464 patients), a pilot combination study (185 patients), and 12 phase II studies (406 patients). The new randomized phase III protocol for advanced soft-tissue sarcoma will provide an interesting test of the validity of the current membership policy, which has not discouraged the participation of enthusiastic new members. For extremity sarcomas, improved surgical techniques have increased the number of patients retaining functional limbs but have maintained excellent rates of local control. However, systemic metastasis remains a significant problem and presents a challenge for future adjuvant studies.
Adult↗