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Biomedical subjects

J F Morere

Publications and source records attributed to J F Morere.

At least 19 recordsLinked to original sources

Vinorelbine and ifosfamide for unresectable non-small cell lung cancer.

PURPOSE: The study assessed the efficacy of combination therapy with vinorelbine and ifosfamide in patients with unresectable non-small cell lung cancer. PATIENTS AND METHODS: Forty patients with non-small cell lung cancer whose tumour was unresectable by virtue of the extent of disease or severity of impairment of lung function and who were considered unsuitable for treatment with a cisplatin based treatment were entered onto the study. Thirty-four patients received two cycles of treatment and were considered to be evaluable for response. The treatment schedule consisted of vinorelbine (Navelbine, Pierre Fabre Medicament) 25 mg/m2 on days 1 and 8, and ifosfamide 2 g/m2 per day with mesna 0.5 g/m2 three times daily given on days 1 to 3; cycles were repeated every 21 days and treatment continued in responding patients until progression occurred. RESULTS: Objective responses were observed in 12 patients (30%; CI95, 16-44) with one completed response (CR) and 11 partial response (PR). CONCLUSION: This schedule achieves good levels of response without the use of cisplatin so it is suitable for patients whose performance status or concomitant medical condition precludes the use of platinum based chemotherapy.

Aged↗

[Treatment of advanced kidney cancer using recombinant erythropoietin].

OBJECTIVES: Study of the antitumour effects of erythropoietin on metastatic renal cell carcinoma. METHODS: After giving their informed consent, 20 patients with histologically proven metastatic renal cell carcinoma received subcutaneous recombinant erythropoietin three times a day at a dose of 150 IU/kg when haemoglobin was less than or equal to 12 g/dL or 75 IU/kg when haemoglobin was higher than 12 g/dL. Treatment was continued for a minimum of 8 weeks before reassessment and was continued thereafter, except in the case of progression or excessive toxicity. A staging assessment was performed every 8 weeks and the response was assessed on the basis of WHO criteria. A clinical and laboratory assessment was performed every two months to evaluate toxicity, graded according to the WHO scale. All but one of the patients had received immunotherapy or chemotherapy prior to inclusion in the study. RESULTS: One complete response (> 12 months), one partial response (8 months), two minor responses, 10 cases of stabilisation and 6 cases of progression were observed. 15 patients received treatment at full doses. In 5 patients, the duration of treatment was reduced before the 8 weeks initially defined because of tumour progression in one patient and because of haemoglobin persistently greater than 15 g/dL in 4 other patients. Adverse effects consisted of 1 case of moderate headache, 2 cases of transient bone pain, and 1 case of transient hypertension. CONCLUSION: Erythropoietin exerts a moderate antitumour effect which needs to be confirmed by a phase II trial of first-line treatment in selected patients.

Aged↗

Somatostatin receptor imaging in small cell lung cancer.

To determine its usefulness, we evaluated 111In-DTPA-Octreotide (octreotide scintigraphy) in the initial staging of 19 patients with histologically proven small cell lung cancer (SCLC) and compared the results to those of conventional imaging. Images performed during initial staging demonstrated 21 known pulmonary lesions and two known supraclavicular nodes. We detected a previously unknown mediastinal lesion. The number of metastases was underestimated, with no liver (5), brain (1) or skin metastases detected. Bone lesions were identified in 4 out of 5 patients. There were fewer lesions detected with octreotide scintigraphy than with bone scintigraphy (except for one case). We therefore conclude that octreotide scintigraphy is a highly effective method for detecting SCLC primary tumour and supraclavicular nodes; the procedure is of limited value for distant metastasis. Further studies are needed to establish its ability for detecting residual intrathoracic disease, and confirm the value of octreotide scintigraphy in differentiating residual disease from other benign lesions.

Adult↗

Sequential functional imaging with technetium-99m hexakis-2-methoxyisobutylisonitrile and indium-111 octreotide: can we predict the response to chemotherapy in small cell lung cancer?

A case of small cell lung carcinoma (SCLC) demonstrating uptake on functional indium-111 octreotide scintigraphy is presented. Technetium-99m hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy clearly delineated an absence of radionuclide uptake at the tumour site. This suggested the presence of multidrug resistance-mediated P glycoprotein (Pgp) on tumour cells, which recognizes certain chemotherapeutic agents as well as MIBI as a substrate and avoids radionuclide concentration. Following three courses of chemotherapy, the patient failed to improve and eventually died. This case demonstrates the importance of functional images, which have the potential to predict the outcome in response to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Cisplatin-5-fluorouracil in small cell lung cancer. A phase II study in 109 patients.

One hundred nine previously untreated patients with small cell lung cancer were treated for five consecutive days with 20 mg/m2/day of cisplatin and 600 mg/m2/day of 5-fluorouracil. One cycle of chemotherapy was administered every three weeks. The patients received a median number of three cycles. Then they were transferred to CAE chemotherapy. A 77% overall response rate (95% confidence interval of 0.70-0.85) was observed after initial cisplatin-5FU treatment. Twenty-three complete responses (21%) and 62 partial responses (56%) were obtained. In cerebral metastases the response rate was high at 91% (21 out of 23), with 43% complete responses. In the limited forms, statistical survival at 1 year was 25%. A Grade 3-4 thrombocytopaenia was observed in 10 patients (9%) and a Grade 2-3 leukopaenia in four patients. Three patients suffered from a Grade 2 cardiac toxicity. The cisplatin-5-fluorouracil combination demonstrates promising initial response rate in small cell lung cancers. Its main interest is in its important action on cerebral metastases and its moderate haematological toxicity.

Adult↗

[Cancer of the kidney: changes in blood lymphocyte subsets induced by treatment with interferon alpha-2b and interleukin-2r].

Twenty patients (6 females and 14 males), age range 36-70 years-old, with metastatic renal cell carcinoma (MRCC), received interferon alpha-2b (IFN-A) 10 x 10(6) units/day IM for 5 days followed by continuous i.v. infusion of interleukin-2 (IL-2) 18 x 10(6) units/day for 5 days. The median follow-up was 10 months. We observed four partial responses (20%), 13 stable (65%) and three progressive diseases (15%). The mean CD4/CD8 ratio, obtained before therapy in patients with MRCC, was compared with CD4/CD8 ratio in 51 patients with different advanced malignancy and in patients with no cancer. The CD4/CD8 ratio was higher in patients with MRCC (2.55) than in other cancers (1.474) and than in populations with no cancer (1.66 x chi 2 = 17,378). The surface phenotypes of peripheral lymphocytes were analysed by cytofluorometry in patients with MRCC during and after treatment with IFN-A and IL-2. Immune modulatory effects of therapy immediately induced a decrease of different sub-populations of lymphocytes except CD25+. Far from the first course, a rise in lymphocyte count was observed. The proliferation effect was as follows: CD4+, CD8+, CD4+ CD45RA- and CD16+ CD8- cells. Far from the second and 3rd course, the sub-populations of lymphocytes decreased, except the CD4+ and CD4- CD45RA+ cells. The CD4/CD8 ratio increased progressively during treatment. Before each course, the CD4/CD8 ratio of patients with response to treatment was higher than the CD4/CD8 ratio of patients with no response. Results were non-significant due to the small number of subjects with responses in this study.

Adult↗

[Malignant melanoma of the uvea].

Intraocular melanoma is the most common primary ocular malignancy in Whites. Epidemiologic studies demonstrated the role of sun exposure as a risk for uveal melanoma. Conservative treatment techniques are indicated for localised tumors when feasible. External radiation therapy and radioactive eye plaque brachytherapy seem as effective as surgery in term of survival. High tumor doses can be safely administered with either helium or proton beams. A partial preservation of the vision is possible in most of patients. However, even for locally controlled patients, distant metastases can occur. Liver is the most frequent metastatic site, and also the first involved. Liver metastases are associated with a low response rate, to dacarbazine and nitrosourea. Recent studies using a new nitrosourea, fotemustine, administered locally through an intra-arterial catheter, show that it produces encouraging results with a good hepatic and hematologic tolerance.

Antineoplastic Agents↗

Inhibitory effect of substituted dextrans on MCF7 human breast cancer cell growth in vitro.

Substituted dextrans can reproduce some of the properties of heparin and can thus be used to alter cellular growth. We studied the effect of heparin (H108), dextran (D), carboxymethylbenzylamide dextran (CMDB) and carboxymethylbenzylamide sulfonate dextran (CMDBS) on the growth of human mammary cells of the MCF7 tumor line. The cells were cultured in minimum Eagle's medium containing 2% fetal calf serum without biopolymer, or with increasing concentrations of H108, D, CMDB or CMDBS. Growth curves were accurately based on cell counting using a Coulter counter. Cell distribution in the various phases of the cycle was analyzed by flow cytometry. Dose-dependent growth inhibitory effects (400-4000 micrograms/ml) were observed. The effect on MCF7 tumor cells was most apparent with CMDBS. The percentage of cells in the S phase decreased with preferential blocking in the G0/G1 phase. Pre-clinical studies can be anticipated as there is an absence of in vivo toxicity.

Aged↗

[Brain metastases of malignant melanomas].

Cerebral metastases of malignant melanoma are correlated with a very poor prognosis. Surgery of an isolated metastase can lead to a long survival but the brain lesions are frequently numerous and associated with an extracerebral diffusion. Dacarbazine (DTIC) gives a mean response rate of 21% on visceral localisations but doesn't cross the blood brain barrier (BBB). Neither do the biological response modifiers like Interleukin 2 (Il2) that leads to 25% response rate in disseminated melanoma. Nitrosoureas like carmustine (BCNU) and semustine (CCNU) have been investigated in different non randomised studies and the clinical results didn't illustrate their theorical ability to cross the BBB. Radiotherapy is also used as a palliative therapy with 7 to 16 weeks survival. Fotemustine (muphoran), a new amino acid linked nitrosourea, can give a response rate up to 28.2% in patients with cerebral metastases and the increased survival of responding patients is significant. The availability of this new drug may suggest associations with surgery and radiotherapy in the future to improve the survival of such patients.

Antineoplastic Agents↗