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M Espie

Publications and source records attributed to M Espie.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Metastatic eye neoplasms. Review of the literature apropos of 4 cases].

Malignant disease metastatic to the eye is a common entity afflicting hundred patients each year. Breast carcinoma is the most common carcinoma responsible for ocular metastases with an estimated range probably closer to 30% and prevalence of 11.000 women by year in United-States. Breast carcinoma is followed by lung cancer and adenocarcinoma of an unknown primary. The diagnosis should be suspected in patient with history of carcinoma and a decreased visual acuity or any other visual symptom. The most useful diagnostic techniques include direct ophthalmoscopy, ultrasonography, computed tomography and magnetic resonance imaging. The cornerstone of treatment of ocular metastases remains radiation therapy. The overall response rates of earlier diagnosis, according to measurement of visual acuity, may be ranged from 72 to 94%. Early diagnosis and treatment of those lesions are a primary concern to maximize the quality of life until death of patients with metastatic disease. We report four cases of women with breast cancer metastatic to the eye.

Breast Neoplasms↗
PubMed1994

p53 mutations and overexpression in locally advanced breast cancers.

Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti-human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (chi 2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (chi 2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53 mutations could be a late event in this non-familial form of breast cancer.

Base Sequence↗
PubMed1994

Megestrol acetate in advanced breast carcinoma.

Hormonal therapy of breast cancer is the oldest treatment in advanced disease. Durable remissions can be obtained with a wide variety of hormonal manipulations. Oophorectomy was first used to reduce endogenous hormonal levels. Surgical procedures have been supplanted by drugs that reduce hormone secretion or block steroid hormone activity. Tamoxifen is the agent most widely used because of few side effects. Agonists can also be effective. Estrogens, androgens, and progestins have the same level of activity as surgical ablation or drug antagonists (20-40% overall response rate). More than 2,000 patients with advanced breast cancer worldwide have been treated with megestrol acetate in clinical trials. Reports of the trials show a response rate of 27%. In randomized trials, efficacy of megestrol acetate is comparable with tamoxifen and with other hormonal treatments. At the standard dose of 160 mg/day, the major side effect is weight gain. Studies are ongoing to evaluate if high doses of megestrol acetate may increase the response rate with acceptable toxicity.

Aminoglutethimide↗
PubMed1994

Taxoids: a new class of cytotoxic agents.

Taxoids (paclitaxel and docetaxel) are a new class of cytotoxic agents. Their mechanism of action (enhanced polymerization of tubulin and inhibition of its depolymerization) acts thereby as mitotic spindle inhibitors. Significant experimental antitumor activity, although more marked with docetaxel, has been observed with both agents. Their main side-effects are reversible non cumulative neutropenia and alopecia; significant hypersensitivity reactions using cortico-steroids antiHT1/2 premedication are seen in < 5% of patients receiving paclitaxel as a pulsed (3 h) infusion; neurotoxicity appears dose-related; docetaxel can induce a peculiar skin toxicity often associated with edema. Paclitaxel at the recommended dose of 175 mg/m2 achieves responses in 20-30% of patients with relapsed ovarian carcinoma; its activity in advanced breast cancer although significant is clearly dose-related with an optimal dose still debatable; responses are observed in approximately 30% of patients with non small cell lung cancer (NSCLC). Docetaxel (100 mg/2) is active in first line treatment of advanced breast cancer (50-72% RR) as well as 2nd line treatment (> 40% RR); an activity in the range of that observed with paclitaxel is reported in NSCLC.

Animals↗
PubMed1993

[Promising results of bimonthly chemotherapy with high dose cyclophosphamide and epirubicin in induction treatment of inflammatory cancer of the breast].

Forty-eight patients with inflammatory breast cancer were treated by an induction regimen with cyclophosphamide (1200 mg/m2), and epirubicin (75 mg/m2). Four to six courses were given every two weeks, whatever the absolute leukocyte counts, before mastectomy, loco-regional radiation, and conventional, or reinforced, for selected patients, chemotherapy. Main toxicity was leukopenia, with grade IV in 25% of cases. However, febrile neutropenia was rare, and relative dose intensity was 102% after four courses, and 97% after six courses. Complete disappearance of inflammatory signs was observed in 90% of patients. Three patients had a pathological complete response, and ten patients had negative axillary lymph nodes. Furthermore, 13 patients had a major pathological response. With a median follow-up of 42 months, progression-free survival and overall survival are 48% and 66%, respectively.

Adolescent↗
PubMed1990

Phase I study of oxaliplatin in patients with advanced cancer.

Oxaliplatin, or trans-1-diaminocyclohexane-platinum, was tested in a phase I study. A total of 44 patients received 116 courses with dose escalation from 45 to 200 mg/m2. Neither renal nor hematologic toxicities were observed at doses up to 200 mg/m2. Gastrointestinal toxicity was practically constant and often of grade 3-4 on the WHO scale (53% of patients). The dose-limiting toxicity was a peculiar sensory neuropathy; the first neurologic phenomena appeared at a dose of 135 mg/m2 and continued thereafter, occurring after 75% of the courses with mild to moderate intensity (WHO grade 1-2 after 67% of the courses). Neurotoxicity was cumulative and six patients developed grade 3 disabling neuropathy after a cumulative dose of 500 mg/m2, with walking and handwriting difficulties being slowly regressive in three cases. A peculiar symptom was the influence of temperature, with exacerbation of parethesias when patients touched cold surfaces. Nerve-conduction studies carried out in six cases showed a predominantly sensory neuropathy with axonal degeneration. No other toxicities were observed, although audiograms were not systematically done. We observed four partial responses that lasted 6-13 months in patients with oesophageal (2 cases), lung (1), and urothelial cancer (1); two of these patients had been pretreated with cisplatin. Since neurologic side effects occur very frequently and may produce a long-lasting sensory neuropathy, for phase II studies we recommend a starting dose of 135 mg/m2, with a careful neurologic survey.

Adult↗
PubMed1990

5HT3-antagonist receptors: their role in drug-induced emesis.

Chemotherapy-induced emesis is the most severe side effect in term of patient's perception. Current anti-emetic regimen as high dose metoclopramide can achieve a complete response in less than 60% of patients. The HT3 receptors appear to be the principal mediator of the emetic effect and their blockade have a clear activity in the prevention of acute drug-induced emesis, superior to reference regimens.

Antiemetics↗
PubMed1989

[Cancer of the breast: intensive treatment with bone marrow autografts].

High dose chemotherapy with autologous bone marrow transplantation has been proposed in metastatic and inflammatory breast cancer. Data in the literature reported an improvement of the quality and of the rate of response. However, the impact on survival remains to be demonstrated. Since 1985, a pilot study in inflammatory and directly metastatic breast cancer has been started in order to determine the impact of high dose chemo-radiotherapy. Patients were treated with an induction regimen consisting of cyclophosphamide 1,200 mg/m2 and 4'epi-adriamycin 75 mg/m2 every 15 days x 4. Mastectomy was performed associated for patients younger than 50 years with bone marrow collection and cryoconservation. In this group, late intensification with cyclophosphamide 2.2 g/m2 day 1 and 2, TBI and autologous bone marrow transplantation was performed. Fourteen patients have been treated: 9 inflammatory breast cancers T4 b N1 M0, 5 metastatic cancers at presentation including 3 with inflammatory breast cancer T4 b N1 M1 and 2 metastatic T2 N1 M1. Relapses had occurred in 7 patients, of them 4 were metastatic. Five patients died from their disease, and one from CMV interstitial pneumonitis. Six patients are alive free of disease but only one was metastatic. On this limited number of patients, survival of metastatic breast cancers does not seem to benefit from this regimen.

Adult↗
PubMed1989

Advances in vinca-alkaloids: Navelbine.

Vinorelbine (Navelbine) is a new semisynthetic vinca alkaloid which chemically differs from vinblastine by substitutions on the catharantine moiety of the molecule. It has shown promising experimental antitumor activity against experimental murine tumors as well as continuous cell lines of human neoplastic origin and human tumor xenografts in nude mice. Acute subacute and chronic toxicity extensively studied in rodents, dogs and primate has shown that hematotoxicity was almost the sole side-effect; neurotoxicity appears very limited. Almost exclusive affinity of NVB for mitotic tubulin and tubulin associated protein accounts for this pattern of toxicity. Phase I and II studies have been conducted in humans. Dose limiting side-effect appears to be neutropenia: the drug is slightly emetogenic, induces little alopecia, almost no neurotoxicity, and no other toxicity. Although preliminary, results of phase II studies already suggest significant activity of NVB in non small lung cancer (33% response rate in 78 evaluable patients), advanced breast cancer (53% response rate in 33 pts without significant chemotherapy for the target progression) and Hodgkin's disease (90% response rate after 4 weekly courses in 31 pts). Thus extensive pharmacological studies and ongoing clinical studies confirm that chemical modifications of the catharantine moiety of vinca alcaloid can lead to active agents with broader spectrum of activity and easily manageable side effects.

Animals↗
PubMed1988

[Organoplatinum compounds. 1987 update].

Cisplatin is one of the best available cytotoxic agents particularly in testicular, ovarian and head and neck cancer. However gastrointestinal and renal toxicities preclude greater utilisation. High dose cisplatin (200 mg/m2) has serious neurological side effects. Carboplatin gives the same therapeutic results as cisplatin in ovarian, small cell lung and head and neck cancers with a better tolerance, the main toxicity being haematological. Iproplatin seems to have no advantage over carboplatin. New derivates such as diaminocyclo-hexane-platinum seem to be promising in preclinical and phase I studies.

Carboplatin↗
PubMed1988

[Isolated internal breast adenopathy. Late recurrence of breast cancer].

Invasion of the internal mammary lymph nodes is common in tumoral pathology of the breast, but an isolated internal mammary lymphadenopathy occurring long after treatment of the primary tumour is a rare event. The authors report one case and discuss the prognostic and therapeutic factors involved.

Adenocarcinoma↗
PubMed1987

Hereditary epidermolytic palmoplantar keratoderma associated with breast and ovarian cancer in a large kindred.

We report a large kindred in which palmoplantar keratoderma occurred in association with breast or ovarian cancer or both. This kindred consisted of 61 members of four generations. Thirty-five individuals had palmoplantar keratoderma, including eight women who also had breast or ovarian cancer or both. Five of the six women with breast cancer and both the women with ovarian cancer have died. The proband presented with a yellowish, uniform hyperkeratosis surrounded by a red border covering the entire surface of the palms and soles. Light microscopic examination showed features of epidermolytic hyperkeratosis, and ultrastructural examination revealed the typical markers for this entity, cytolysis and clumps of keratin filaments. This kindred is the first, to our knowledge, to have an association of epidermolytic hyperkeratosis and internal malignancy.

Adult↗
PubMed1987

[Value of initial chemotherapy in the treatment of advanced cancers of the uterine cervix].

Eleven patients who had advanced cancer of the cervix were treated with combination chemotherapy containing Cisplatin as a primary treatment. The cases were: 3 stage II B N+, 2 stage III not involving the bladder, 3 stage III involving the bladder and 3 stage IV. The response rate was 40% with 6 patients responding. The response was better than 50% in 3 and there were 5 failures. In the 6 patients where the treatment was helpful, 2 could have extended surgery whereas the others had follow-up radiotherapy without developing urinary fistulae. Just as it to be found in the literature, it was not possible to pick out prognostic criteria for sensitivity to chemotherapy. A protocol for treatment is suggested, starting with a therapeutic test of chemotherapy. If this is successful it should be followed by extended surgery or radiotherapy. It if is not successful, conventional treatment with radiotherapy will be undertaken. It is essential to carry out multicentre studies in future to find out whether this attitude is going to be successful.

Adult↗