PubMed Health⌕ Search

Biomedical subjects

J M Extra

Publications and source records attributed to J M Extra.

At least 55 records · Page 3Linked 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

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

Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion.

Taxotere (N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl Taxol; RP 56976; NSC 628503) is a semisynthetic analogue of Taxol. It is twice as active in inhibiting tubuline depolymerization and has a better in vivo activity on B16 melanoma, with responses in advanced colon 38 and PO3 adenocarcinoma. Sixty-five patients (49 women, 16 men), with a median age of 57 years, received 248 courses of Taxotere given as a 1-2-h i.v. infusion every 2 or 3 weeks. Ten distinct dose levels from 5 to 115 mg/m2 were studied. Dose-dependent, reversible neutropenia was the limiting toxicity. Delayed and cumulative skin reactions occurred beyond 70 mg/m2. Alopecia was observed in the majority of patients beyond 70 mg/m2. Four partial responses were achieved in patients with ovarian carcinoma, breast carcinoma, small cell lung cancer, and carcinoma with unknown primary. The pharmacokinetics of Taxotere, determined in 23 patients receiving 20 to 115 mg/m2, was linear. At the highest doses, the Taxotere plasma profile was typically triphasic, with a terminal half-life of 13.5 +/- 7.5 (SD) h, a plasma clearance of 21.1 +/- 5.3 liters/h/m2, and a distribution volume of 72 +/- 40 liters/m2. AUC correlated with the percentage decrease of neutrophils in a sigmoid Emax model. The renal excretion of unchanged Taxotere was very low (< 5% of the dose). The recommended dose for phase II trials with this schedule is 100 mg/m2 every 3 weeks.

Adult↗
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↗
PubMed1993

[High dose chemotherapy with autologous bone marrow transplantation in ovarian adenocarcinoma].

The present treatment of advanced ovarian adenocarcinoma patients is unsatisfactory, with 5-year survival rates of less than 15%. To obtain better results, one possibility is the use of therapeutic intensification with autologous bone marrow support. In effect, there is a known dose-response relationship in ovarian carcinoma, especially with alkylating agents. To date, a 69% response rate has been achieved with this kind of treatment in 39 patients refractory to standard therapy. However, responses are of short duration, with a median range of 6-7 months. Therapeutic intensification has been used in over 100 patients, as consolidation therapy, following first-line chemotherapy. For these patients, projected 3-year overall survival and disease-free survival rates are 30-50% and 20-40% respectively. These results compare favorably to those of standard therapy. Early deaths are more frequent in refractory patients (18%). Complete hematological recovery usually occurred within 3-4 weeks. Extra-hematological toxicity is related to previous treatment and to cytotoxic drugs used during intensification. These preliminary results, limited to a small series of patients, are sufficiently promising to continue and extend these trials.

Adenocarcinoma↗
PubMed1992

A review of the antitumour activity of vinorelbine in breast cancer.

The use of vinorelbine 30 mg/m2/week as a single-agent treatment in advanced breast cancer has achieved response rates of > 20% as second-line treatment and 40 to 50% as first-line treatment. The major toxicity of the drug is reversible neutropenia; 35 to 50% of treated patients have grade IV neutropenia. The agent did not induce thrombocytopenia and proved mildly emetogenic and neurotoxic. Activity was confirmed in combination with fluorouracil or doxorubicin, when response rates ranging from 60 to 74% were achieved. Thus, vinorelbine appears to be a promising agent in the treatment of advanced breast cancer.

Adult↗
PubMed1992

[Esophageal cancer: did combined treatments improve prognosis?].

Prognosis of esophageal cancer is very poor. Five-year survival does not exceed 20% after radical surgery, the best available treatment. Unfortunately, only 40% of the patients are amenable to surgery because of poor general status and/or locoregional extension. Adjuvant treatment did not yield survival improvement. Preoperative radiotherapy (three randomized trials) or postoperative radiotherapy (one randomized trial) showed only a decrease of regional relapses, perhaps only for the nodes negative patients. Neoadjuvant chemotherapy obtains some interesting response rate (20-60%), but there has been no evidence yet for survival improvement. Recently, promising results were presented after combination of radiotherapy and chemotherapy. In this paper, we review the present status of combined treatment for esophageal cancer. Our multicentric group (OSOF) is now completing a phase II trial, that should soon form the basis for a phase III prospective study.

Combined Modality Therapy↗
PubMed1991

Non-Hodgkin's lymphoma with cardiac presentation: evaluation and follow-up with echocardiography and MR imaging.

Cardiac presentation of non-Hodgkin's lymphoma is rare and usually associated with a short survival. Two cases were documented and followed-up with echocardiography and magnetic resonance imaging (MRI). The tumoral masses were accurately delineated by MRI. A non-delayed diagnosis ensued and, in association with a multiple drug antimitotic therapy, an improved prognosis obtained.

Adult↗
PubMed1991

Surgical restaging of advanced Hodgkin's disease after first line chemotherapy.

47 patients with stages IIIB and IV Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first-line chemotherapy (CT) which included 4 cycles of CT ABV/IMEP/PCAV/ABV. After surgical restaging (SR), all patients were scheduled to receive 2 additional cycles IMEP/PCAV followed by TNI 20 Gy and patients with residual clinical abnormality or positive restaging surgery received a 20 Gy boost to these areas. 11 patients (23.4%) were found to have active disease in the spleen (10 patients) and/or the lymph nodes (3 patients) after SR. In the spleen, foci of active disease had a size in millimeters and confirm the limits of clinical restaging. According to the response to CT, 5 of the 35 patients (14%) clinically restaged as good responders had active disease; 6 of the 12 patients (50%) clinically restaged as poor responders had active disease. SR is of interest in selected patients with slowly responding disease to determine the indication of an extended field RT for responding patients and salvage therapy for patients resistant to CT.

Adult↗
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↗