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Biomedical subjects

M Espie

Publications and source records attributed to M Espie.

13 recordsLinked to original sources
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↗