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Biomedical subjects

M Aapro

Publications and source records attributed to M Aapro.

At least 55 records · Page 3Linked to original sources
PubMed1995

Docetaxel in advanced ovarian cancer: preliminary results from three phase II trials. EORTC Early Clinical Trials Group and Clinical Screening Group, and the MD Anderson Cancer Center.

Docetaxel has been evaluated in 293 patients with advanced ovarian cancer in three phase II trials. All patients had previously received cisplatin and/or carboplatin as first-line treatment. In all three studies, treatment comprised docetaxel 100 mg/m2 as a 1 h intravenous infusion every 3 weeks, without premedication for hypersensitivity reactions or emesis. To date, 200 patients are evaluable for response. Of these, 63 patients achieved complete or partial response, giving an overall response rate of 31.5% (95% confidence interval 24-39%) for all evaluable patients, or 21.5% for all patients entered in the studies. Of the 57 patients whose disease had progressed either during previous therapy or within 4 months of discontinuing previous therapy, 13 (23%) responded to docetaxel (EORTC data). Major adverse effects of docetaxel observed in approximately half the patients (particularly those who received more than four courses) included skin reactions and fluid retention. Grade III or IV neutropenia was common but short-lived. Severe acute hypersensitivity reactions occurred in approximately 5% of patients. Docetaxel now warrants evaluation as part of first-line therapy. Studies aimed at reducing the incidence of fluid retention and skin reactions with docetaxel are ongoing.

Adult↗
PubMed1994

Weekly carboplatin and VM-26 for elderly patients with small-cell lung cancer.

BACKGROUND: Elderly patients are excluded from chemotherapy trials, even though they represent 25% of those with small cell lung cancer. An effective chemotherapy regimen with limited toxicity should be developed with the aim not only of increasing the survival of these patients, but also of improving their quality of life and their independence. PATIENTS AND METHODS: Twenty-four patients with a median age of 72 years and small-cell lung cancer (SCLC) were included in the trial. Chemotherapy consisted of a weekly intravenous regimen of Carboplatin 80 mg/m2 and Teniposide 80 mg/m2 administered on an outpatient basis. RESULTS: Eight patients had limited and 16 extensive disease. After a median of 12 chemotherapy courses (2-31) the overall response rate was 66.7% (95% Cl: 44.7-84.4), with 5 patients in complete and 11 in partial remission. The median overall survival was 33 weeks, with 4 patients alive at more than one year. Improvement of symptoms occurred in 86% of patients. Toxicity, mainly hematological, was moderate. CONCLUSIONS: Weekly Carboplatin and VM-26 is an effective and non-toxic regimen for elderly patients, leading to results similar to those obtained with a more intensive regimen in a younger age group.

Aged↗
PubMed1993

Commission of the European Communities "Europe Against Cancer" Programme. European school of oncology advisory report. Cancer treatment in the elderly.

Within the EC approximately one million cases of cancer are diagnosed every year. At present, more than 55% of cancers occur in subjects aged over 65 years. There has been little clinical attention to the problem of neoplasia in the elderly. They are not receiving the same standard of specialised oncological care as younger patients. Other diseases (co-morbidity conditions) associated with cancer, and influencing its treatment and outcomes are not being properly considered. Information on surgery, radiotherapy and chemotherapy in younger patients exists for all cancers and could be adapted for the elderly. Controversial aspects of neoplasia in the elderly concern the intensity of chemotherapy, extent of surgery and the relative roles of specialised cancer centres, community hospitals and primary care providers. Future research should aim to replace subjective opinions on presence of frailty with objective instruments such as the multidimensional geriatric assessment scale. New trials could then seek to improve treatment in well-defined populations in terms of both efficacy and quality of life. Funding priorities should firstly consider that clinical trials for tumours in the elderly must be organised from cancer institutes and specialised referral centres in collaboration with geriatricians, primary care and community hospital physicians. Continuing education of doctors should be reported. A document such as this with appropriate modifications might be used as an initial message on neoplasia in the elderly to be published for information to clinicians and the public throughout Europe. Specific measures of quality assurance need financial support to evaluate the improvements in patterns of care. The 10 points of the 'Europe Against Cancer Guidelines' need reemphasising.

Aged↗
PubMed1993

Early clinical trial of MDL 73.147 EF: a new 5-HT3-receptors antagonist for the prevention of chemotherapy-induced nausea and vomiting.

BACKGROUND: Like MDL 72.222, one of the first selective 5-hydroxytryptamine3 (5-HT3) receptors antagonist discovered, MDL 73.147 EF has been shown to possess antiemetic properties in the ferret model. We conducted a phase I study with MDL 73.147 EF in 31 patients, treated with emetogenic drugs over one to five days (cisplatin, cyclophosphamide, doxorubicin, dacarbazine). PATIENTS AND METHODS: 5 groups of at least 5 patients received rising unit doses of MDL 73.147 EF (10 to 50 mg) intravenously before chemotherapy, with two more doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting recorded by an independent observer. RESULTS: 51.6% of the patients were complete responders on day one and 40% on days two to five. One patient was given other rescue antiemetic therapy. Adverse events included constipation (25.8%), mildly elevated blood pressure (12.9%) and other minor events. No extrapyramidal effects have been reported. There was no suggestion of dose-dependent efficacy at the dose levels studied in this limited set of patients. CONCLUSIONS: We conclude that MDL 73.147 EF is a well tolerated and possibly effective antiemetic.

Adolescent↗
PubMed1992

Phase II study of tauromustine in malignant glioma.

46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.

Adult↗
PubMed1991

Loss of heterozygosity for the short arm of chromosome 11 (11p15) in human milk epithelial cells immortalized by microinjection of SV40 DNA.

We have developed, by microinjection of SV40 DNA into human milk epithelial cells, a new mammary cell line, Hu-MI, which exhibits the phenotype of luminal cells or so-called "breast cancer precursor cells." This cell line retains the phenotype of primary cells as demonstrated by the expression of keratins 18 and 19 and of polymorphic epithelial mucins. However, the cells do not grow in agar after more than 80 passages, nor do they form tumors in nude mice. Established cells contain 2 copies of SV40 DNA integrated into the cellular genome and up to 14 copies of free SV40 DNA. A deletion of the short arm of chromosome 11 (11p15) including the c-Ha-ras and the beta-globin genes was found in the immortalized cells when the DNA from these cells was compared to the DNA from peripheral blood mononuclear cells obtained from the same donor. In addition, this cell line showed a good transfection efficiency for other DNA sequences using classical transfection and selection techniques with a neomycin resistance gene (pKOneo). Selective microinjection of DNA into tumor precursor cells may prove useful for the study of the molecular mechanisms involved in breast carcinogenesis. The possible significance of the loss of 11p13-15 in malignant progression of breast cancer is discussed.

Aneuploidy↗
PubMed1990

Effects of recombinant human erythropoietin in infants with the anemia of prematurity: a pilot study.

In an attempt to stimulate endogenous erythrocyte production and thereby provide an alternative to erythrocyte transfusions, we administered recombinant human erythropoietin (rHuEpo) in doses of 75 to 300 units/kg/wk to seven infants with the anemia of prematurity. Treatment was started between 21 and 33 days of life, maintained for 4 weeks, and was well tolerated. All the patients had low baseline serum erythropoietin levels. After rHuEpo therapy, the number of reticulocytes increased from a mean baseline count of 75 x 10(9)/L to 95, 141, and 165 x 10(9)/L on days 7, 10, and 14 of therapy, respectively. Correction or stabilization of the anemia was observed in six of seven patients, whose estimated total erythrocyte volume increased by 49% during therapy (vs a predicted increment of 18% in the absence of rHuEpo). In one patient, however, the hematocrit declined during the treatment, and in three of the responders a secondary fall in hematocrit was noted either during therapy or after its discontinuation. Serum iron and ferritin levels rapidly decreased after the initiation of rHuEpo therapy, and in most patients transient early thrombocytosis and late neutropenia were observed. These data suggest that rHuEpo may correct or stabilize the anemia of prematurity. Its effects, however, may be limited by a variety of factors, among which iron availability probably plays an important role. Controlled studies will be needed to confirm these preliminary observations.

Anemia↗
PubMed1990

Histiocytic necrotizing lymphadenitis or Kikuchi's disease. Anatomo-clinical study of 4 cases.

Histiocytic necrotizing lymphadentis (HNL) is an uncommon clinical and histologic entity, essentially diagnosed in Japan since 1972. The clinical picture is usually characterized by cervical lymphadenopathy and fever, females being more often affected. Leukopenia and elevated erythrocyte sedimentation rate are frequent. The etiology is still unknown, but a viral origin is most likely. The clinical course is always favorable without treatment, except in one case. The histological picture, with necrotic foci surrounded by histiocytes, immunoblasts, small T lymphocytes and plasmacytoid monocytes (so-called plasmacytoid T cells), is characteristic. Nevertheless, HNL may be mistaken for malignant lymphoma both clinically and histologically. We report 4 cases of HNL. One of these presented severe leukothrombopenia; the serum of this patient significantly suppressed the maturation of granulocytic precursor cells in the bone marrow.

Adolescent↗
PubMed1989

Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas.

We have analyzed genomic DNA sequences from 125 prospectively collected single unilateral primary breast carcinoma samples for the presence of alterations of c-myc, c-erbB-1, c-erbB-2, c-Ki-ras and c-Ha-ras protooncogenes. Amplification of the c-myc gene was found in 18% of the samples, and in one sample a non-germ line c-myc related DNA fragment or rearrangement was detected. We have found a significant association (P = 0.0010) between amplified c-myc gene and inflammatory carcinoma, a particularly aggressive breast cancer. The c-erbB-2 gene was amplified in 22% of the tumor samples and a rearrangement was observed once. Alteration of the c-erbB-2 gene was significantly linked to histological grade III tumors (P = 0.005) and the absence of estrogen and progesterone receptors (P = 0.036). No amplifications were observed for c-erbB-1, c-Ki-ras, and c-Ha-ras genes. About 40% of breast carcinomas contain either amplified c-myc or c-erbB-2 protooncogenes, whereas simultaneous amplification of both was seen in only one sample, suggesting the involvement of two distinct molecular mechanisms in breast cancer. Comparison of DNA from peripheral blood and tumor samples indicated loss of one c-Ha-ras allele in 29% of patients heterozygous for this polymorphism. A significant correlation (P = 0.016) between c-Ha-ras locus (11p14) allele loss and patient survival was found. These data suggest that 11p14 allelic loss plays a role in the evolution of human breast cancer, amplification of c-erbB-2 gene is associated with increasing stage of malignancy, and alteration of the c-myc gene in inflammatory breast carcinoma may contribute to the rapid progression of this human tumor subtype.

Blotting, Southern↗
PubMed1989

ABLETOP, a well-tolerated, effective regimen for relapsing Hodgkin's disease. Swiss Group for Clinical Cancer Research (SAKK).

ABLETOP, a salvage regimen for relapsing Hodgkin's disease consisting of adriamycin, bleomycin and etoposide, has been evaluated in 18 patients, 16 of whom were evaluable for toxicity and 15 for response. Fourteen patients showed maximal grade II nausea and vomiting, whereas 13 patients had grade III/IV alopecia. The median leukocyte nadir was 3.1 x 10(3)/mm3. Twelve of 15 patients evaluable for response reached a complete or partial remission; 10 of 12 pretreated patients reached a remission, 5 a complete remission and 5 a partial remission, for an overall response rate of 83%. We conclude that ABLETOP is a well-tolerated effective regimen for relapsing Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Neo-adjuvant radio-chemotherapy of epidermoid carcinoma of the esophagus].

In spite of progress in surgery and radiation therapy, esophageal squamous cell carcinoma's outlook remains grim with a cure rate of approximately 10%. The high failure rate is not only due to loco-regional failure but also to distant metastasis. The association of preoperative chemotherapy with radiation has gained interest with hope to improve control of this disease. The present pilot study is an alternating treatment of chemotherapy and radiotherapy for poor risk carcinomas of the esophagus, not primarily amenable to surgery. The chemotherapy is composed of Cis-Platinum 60 mg/m2 Day 1 (D), Mitomycin 8 mg/m2 D1 and Vindesin 3 mg/m2 D1 and D8, alternating with radiotherapy twice 20 Gy in fraction of 2 Gy per day. After reevaluation patients are if possible submitted to surgery and if not, to a third course of treatment to a total of 3 courses and 60 Gy. Seventeen patients were entered in our study with 15 evaluable. The radiochemotherapeutic association was overall well tolerated with no toxic deaths due to treatment. Seven patients had symptomatic improvement after the first treatment cycle. The presurgical evaluation showed 8 CR and 3 PR. Eight patients have been operated with 3 pathological CR and 3 PR. Five patients completed the 3 courses of chemo- and radiotherapy (without surgery) with no improvement compared to the workup before the third course. The survival is as follows: among the 8 operated: 4 are alive without evidence of disease and 4 are dead with 2 postoperative deaths and 1 local recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗