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Biomedical subjects

J P Droz

Publications and source records attributed to J P Droz.

At least 19 recordsLinked to original sources
PubMed1992

Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms.

The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor markers for nongonadal malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free hCG alpha and hCG beta subunits have been used to reevaluate the presence of these molecules in the serum of patients with a wide variety of tumors. Serum samples from patients with newly diagnosed, persistent, or recurrent malignancies of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors (n = 309), and nonmalignant disease controls (n = 86) were studied using four highly specific and sensitive monoclonal based immunoradiometric assays to hCG and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found to be common in cancer patients, normal subjects, and disease controls. However, serum levels greater than 1000 pg/ml were highly diagnostic of gonadal tumors and specifically identified nonseminomatous testicular tumors. Significant serum elevations of free hCG alpha subunit (as high as 3000 pg/ml) were found in approximately 96% of cancer patients, normal individuals, and disease controls. In contrast, free hCG beta subunit levels (greater than or equal to 100 pg/ml) were detected in 70 and 50% of patients with nonseminomatous and seminomatous testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and 30% of cervical carcinomas. All normal subjects and disease controls had free hCG beta levels less than 100 pg/ml. Thus, the detection of the free hCG beta subunit in serum of nonpregnant subjects was highly diagnostic of malignancy in general and specifically defines a subgroup of aggressive nongonadal malignancies.

Adult↗
PubMed1992

[Biopathology of renal cancer in adults].

Most renal cancers are clear cell adenocarcinoma. The classification is based on the tumor size, the renal vein and lymph node involvement, and metastases. Renal cancer originates from the proximal convoluted tubule. The murine Renca tumor and the Wistar-Lewis rat renal adenocarcinoma are experimental models which well reproduce the evolution of the human renal cell carcinoma. They allow the study of the effect of chemotherapeutic agents, of lymphokines and of transfected cytokines. However, experimental models have limited value.

Adult↗
PubMed1992

[Renal cell cancer: oncogenes and tumor suppressor genes].

Recently, there has been a significant increase in the knowledge about the molecular basis of renal cell carcinoma. Its sporadic form is characterized by a deletion on the short arm of chromosome 3, even for localized stages. The same genetic abnormality is found in renal cell carcinomas associated with the von Hippel-Lindau disease. Such findings strongly suggest the presence of a common tumor suppressor gene which seems involved in the genesis of sporadic renal cell carcinoma and in the predisposition of hereditary cancers. Other tumor suppressor genes located on other chromosomes, as well as over expression of growth factors, seem to be related to the progression of this malignancy. Further studies of the molecular events associated with cellular transformation should help to better understand the behavior of such cancers and to find new therapeutical approaches.

Carcinoma, Renal Cell↗
PubMed1992

[Therapeutic strategy in metastatic renal cancer].

Prognostic factors have been described in metastatic renal cell cancer: performance status, weight loss, elevated erythrocyte sedimentation rate, presence of liver metastases. The treatment for a patient with good prognosis consists of: surgical exeresis of solitary metastasis, immunotherapy by either interferon or interleukin 2. Treatment in case of a rom prognosis is a combination of supportive care, orthopedic surgery for pathologic fracture or medullar compression, antalgic radiotherapy, embolization, nephrectomy for hematuria, and analgesic treatments.

Blood Sedimentation↗
PubMed1992

[Gestational trophoblastic tumors].

The term gestational trophoblastic tumours covers hydatidiform moles, invasive moles and choriocarcinomas. These are rare diseases remarkable for their high chemosensitivity. The current objective is to cure all patients while preserving their potential for child bearing. Several studies have elicited prognostic factors, so that treatment can be adjusted to each individual patient. Advances in immunochemistry have led to the discovery of a highly reliable marker (HCG and beta-HCG) which has proved valuable to confirm the diagnosis and to follow the patients during and after treatment.

Choriocarcinoma↗
PubMed1992

Phase I clinical trial and pharmacokinetic evaluation of doxorubicin carried by polyisohexylcyanoacrylate nanoparticles.

Doxorubicin (DXR) incorporated into biodegradable acrylate nanoparticles such as polyisohexylcyanoacrylate (PIHCA) has been shown to increase DXR cytotoxicity and reduce cardiotoxicity by modifying tissue distribution in preclinical studies. We have conducted a phase I clinical trial of DXR-PIHCA in 21 patients with refractory solid tumors (10 male, 11 female, median age: 53 years, median PS: 1, prior free-DXR therapy: 7 patients). A total of 32 courses at 28 day intervals were administered at 6 dose levels (15, 30, 45, 60, 75 and 90 mg/m2). The drug was given as a 10 minute IV infusion on day 1 to the first 5 patients: 2 of them presented a grade 2 allergic reaction (W.H.O. criteria) during infusion, which was rapidly reversible once drug administration was discontinued. Subsequently, in the other 16 patients, the administration was modified to a 60 minute i.v. perfusion diluted in 250 cc of Dextrose 5%: only 1 patient presented the same allergic reaction. Grade 2 fever and vomiting occurred in 9 patients and 7 patients respectively during the first 24 h after treatment. There was no cardiac toxicity among the 18 evaluable patients. Grade 3 or 4 hematologic toxicity occurred at the 75 and 90 mg/m2 dose level. The dose limiting toxicity was neutropenia. The maximum tolerated dose was 90 mg/m2 and the recommended phase II dose was 75 mg/m2. A pharmacokinetic evaluation of DXR-PIHCA was conducted in 3 patients each at a different dose level (60, 60 and 75 mg/m2) and was compared with free DXR given to the same patients in the same conditions.

Adult↗
PubMed1992

Phase II trial of pirarubicin in the treatment of advanced bladder cancer.

Doxorubicin is one of the standard drugs in the chemotherapy of advanced urothelial tumors. Pirarubicin, a new anthracycline, turned out to be equally active and less toxic than its parent compound in preclinical studies. Twenty one patients with either metastatic or inoperable locally advanced bladder carcinoma were treated with intravenous infusion of pirarubicin: 25 mg/m2/day for 3 days every 4 weeks in the first 15 patients and 20 mg/m2/day for 3 days every 3 weeks in the others. Fifteen patients were not pretreated and 6 received prior chemotherapy (5 patients with doxorubicin containing regimen). Twenty patients were evaluable for response; there were 2 partial response, 8 stable disease and 10 progressive disease. All pretreated patients progressed. Hematological toxicity was moderate, however there was one toxic death with grade 4 neutropenia which occurred in a heavily pretreated patient receiving a dose of 25 mg/m2/day for 3 days. There was no clinical cardiac toxicity. Single agent Pirarubicin displays an objective response rate of 10% (95% of CI 0 to 23%) which reaches 14% (95% CI 0 to 29%) when non pretreated patients are analyzed separately. This rate is in the range of doxorubicin activity.

Adult↗
PubMed1992

Ovarian dysgerminoma metastatic to the breast.

A 16-year-old girl underwent a right salpingo-oophorectomy for a pure dysgerminoma limited to the right ovary. One month later, she developed a right pelvic mass along with abdominal lymphadenopathies, peritoneal carcinomatosis, left breast mass, and left axillary node. Cytology of the breast mass was suggestive of a pure dysgerminoma. Breast metastases of epithelial ovarian carcinoma are uncommon. In the literature, this is the first case of a breast metastasis of an ovarian dysgerminoma.

Adolescent↗
PubMed1992

Non-nephrotoxic empiric antimicrobial therapy in febrile neutropenic cancer patients.

We evaluated the efficacy of piperacillin-pefloxacin as a non-nephrotoxic antibiotic combination in febrile neutropenic cancer patients treated with nephrotoxic chemotherapy. 40 patients: 34 with solid tumours and 6 with non-Hodgkin lymphoma, were treated during 55 episodes with: piperacillin 4 g intravenously every 8 h and pefloxacin 400 mg intravenously every 12 h. If the patient remained febrile after 72 h, 1 g vancomycin intravenously was added every 12 h. The mean duration of neutropenia was 7 days (range 3-13). Infection was microbiologically documented in 13 episodes (8 gram-positive cocci and 7 gram-negative bacilli). Temperature became normal in 38 patients with piperacillin-pefloxacin and 12 further episodes were resolved by the addition of vancomycin. 2 patients had an early change of antibiotics because of clinical deterioration, there were 2 protocol violations and 1 patient's temperature became normal after the addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and warrants further comparative trials.

Adolescent↗
PubMed1992

Vinblastine in metastatic renal cell carcinoma: EORTC phase II trial 30882. The EORTC Genitourinary Group.

32 patients with metastatic renal cell carcinoma (MRCC) who had had no prior chemotherapy received vinblastine 0.15 mg/kg intravenously once weekly for 6 weeks, thereafter every second week, provided no major toxicity. Dose modifications were based on haematological and neurological side-effects. Only one complete response was observed among 26 evaluable patients (response rate: 4%; 95% confidence interval: 0-20%). 4 out of 29 patients developed grade 3 leukopenia. Grade 3 peripheral neurotoxicity was recorded in 2 patients. 2 patients had grade 3 alopecia. Vinblastine has no major significance on the clinical management of MRCC.

Adult↗
PubMed1992

Monoclonal antibodies to the free beta-subunit of human chorionic gonadotropin define three distinct antigenic domains and distinguish between intact and nicked molecules.

The present study was designed to characterize monoclonal antibodies (mAbs) specific for the free beta-subunit of hCG (free hCG beta), to develop two-site immunoradiometric assays (m-IRMAs) specific for free hCG beta, and to study the reactivities of various molecular forms of hCG beta in these assays. We attempted first to delineate the antigenic regions present specifically on the free hCG beta by studying the binding pattern of seven mAbs directed preferentially to hCG beta, designated FBT11, P8E, P10F, HB2, P5D, P5H, and INN-64. Competitive inhibition experiments performed by RIA demonstrated the specificity of these mAbs for the free hCG beta as noncross-reacting with the beta-subunit of human (h) LH beta. m-IRMAs were used to analyze the arrangement of epitopes on hCG beta. Experiments performed with the seven mAbs used either as capture antibodies or radiolabeled indicators confirmed the specificity of the seven mAbs for the free hCG beta, and that mAbs FBT11, P8E, and P10F bound to equine LH beta (eLH beta), but did not bind to a fragment of hCG beta called the beta-core fragment (beta CF). These antibodies defined an antigenic domain identified as A. In contrast, mAb HB2 bound neither to eLH beta (e beta) nor to beta CF and was directed to domain B (e beta negative, beta CF negative). Finally, mAbs P5D, P5H, and INN-64 bound to beta CF, but did not bind to eLH beta, and defined a third domain identified as C (e beta negative, beta CF positive). Collectively, these results demonstrate that at least six antigenic domains are present on the free hCG beta and that a limited set of amino acids was shared among these domains; domains A, B, and C are present only on the free beta-subunit, while three other domains recognized by mAbs FB19, FBT10, and 518B7 are present on both free hCG beta and hCG. Thus, most of the surface of the hCG beta appears to be antigenic and accessible to antibody binding. Three different m-IRMAs specific for free hCG beta were then constructed using either mAb FBT11 (domain A) or HB2 (domain B). The study of the reactivities of various molecular forms of hCG beta in these assays demonstrated that the recognition of hCG beta forms nicked at position 43 (beta 43), 44, and/or 51 (beta 44/51) varied between assays.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Primary mediastinal germ cell tumors. Results of a French retrospective study.

Eighty-seven patients with primary mediastinal germ cell tumors treated between 1983 and 1990 were studied. Among the 23 patients classified as pure seminoma, eight (35 percent) underwent surgery followed by radiotherapy (n = 6), radiotherapy and/or chemotherapy (n = 2); two patients underwent radiotherapy; 13 patients (57 percent) underwent induction cisplatin-based chemotherapy (ten complete responses) followed by radiotherapy (n = 9), second line chemotherapy (n = 2) and surgical resection of residual tumor (n = 2). On completion of treatment, 22 patients (96 percent) with seminoma were free of disease. The two-year Kaplan-Meier survival rate of these patients was 86 percent. Among the 64 patients with nonseminomatous germ cell tumor, 19 patients (30 percent) underwent surgery as first treatment (ten complete resections) followed by chemotherapy (n = 17) and radiotherapy (n = 5). On completion of treatment, 12 of 19 patients were disease free. Forty-five patients (70 percent) underwent induction cisplatin-based chemotherapy (ten complete responses), and 22 of them underwent resection of residual tumor (19 complete resections). Twenty-three patients were treated with first line chemotherapy without postchemotherapy surgery (three complete responses). In summary, 33 patients (52 percent) with nonseminomatous germ cell tumors became free of disease, and seven patients (21 percent) relapsed after achieving a complete response. The two-year Kaplan-Meier survival rate of the nonseminomatous germ cell tumor patients was 53 percent (87 percent if a complete response), with a median survival of 28 months. Despite a worse prognosis than nonseminomaous tumors from other primary sites, this series of mediastinal germ cell tumors has confirmed the efficacy of therapy.

Adult↗
PubMed1992

[Brain metastasis of choriocarcinoma in males. Apropos of a case. Review of the literature].

A 22 year-old male patient had a choriocarcinoma of the mediastinum metastatic to the brain, liver, lung and skin. He was treated with five cycles of chemotherapy containing cisplatinum, vinblastine, VP16 and bleomycin and he achieved a partial remission. Then he developed a progressive disease exclusively located to the brain and he died of an intracranial hemorrhage. The autopsy showed the mediastinum and the lung being free of residual trophoblastic tumor. Pure choriocarcinoma is rare in males, but brain metastases are frequently present in this case. Therapeutic guidelines are uncertain, so they must refer to the experience obtained in gestational choriocarcinoma. Two groups of patients are individualized both in male germ cell tumors and in placental choriocarcinoma: one group of patients with brain metastases at diagnosis, with a better prognosis, and one group of patients with brain metastases occurring in the course of the disease, with a poor outcome. The risk of intratumoral hemorrhage is common to all varieties of choriocarcinoma brain metastases and is not lowered by greater effectiveness of the chemotherapy. Brain metastases found at the moment of the choriocarcinoma diagnosis require chemotherapy and radiotherapy and in some selected cases, a surgical removal.

Adult↗
PubMed1992

Burkitt's lymphoma in adults: a retrospective study of 46 cases.

The prognosis of Burkitt's lymphoma is generally considered to be poor, particularly in the advanced stages of the disease. Although recent chemotherapy protocols have given high rates of cure in children, there are few such reports concerning adults. We therefore conducted a retrospective analysis of the results for treatment of 46 adults in the Institut Gustave Roussy (IGR) between 1978 and 1987, in order to establish an effective treatment strategy for use in a prospective trial. The median age of the patients was 31 years and the majority were Caucasians of European origin. The clinical symptoms and course of the disease were similar to those in the pediatric situation and corresponded to the so-called non endemic forms observed in Europe and the United States. Presentation was generally extra-nodal, usually with abdominal manifestations. As a rule, the disease progressed rapidly and showed a high affinity for the central nervous system in the absence of specific prophylaxis, despite systemic therapy with highly active agents, particularly in the advanced stages. According to Murphy's classification, there were 6 stage I, 11 stage II, 19 stage III and 10 stage IV patients (3 of whom had CNS involvement). Treatment was heterogenous, although all the patients received polychemotherapy including anthracyclins. The best results were obtained from eleven patients treated according to the French Multicenter Protocols for pediatric Burkitt's lymphoma (LMB-84 and LMB-86). Kaplan-Meier 5-year relapse free survival rate among the 46 patients was 42% (stage I: 83%; stage II: 67%; stage III: 30%; stage IV: 30%). In order to standardize our therapeutic approach, we started a prospective study in 1988 using the unmodified pediatric protocol for our adult patients.

Adolescent↗
PubMed1992

Infectious complications associated with granulocytopenia during the treatment of poor risk or relapsed germ cell tumors.

Infectious complications associated with granulocytopenia during the treatment of poor risk or relapsed germ cell tumors were studied in order to assess the frequency, morbidity and characteristics of these complications. Thirty-three cases were investigated at the Institut Gustave-Roussy; 63 episodes of granulocytopenia were observed (mean duration 7.5 days). Twenty-four (38%) of the episodes of granulocytopenia were associated with fever. In 11/24 episodes (46%), fever was associated with a documented infection. Eighteen organisms were isolated. Ten were found to be Gram-positive, 7 Gram-negative, and one Candida. The major site of infection was the lungs. One death from septicaemia occurred. In conclusion, post-chemotherapy granulocytopenia during the treatment of germ cell tumors is associated with fever in less than 50% of cases. Bacterial infection was diagnosed in only 46% of febrile neutropenic episodes and rarely appears to be associated with a fatal outcome.

Adolescent↗
PubMed1992

[The use of antiemetics in cancer chemotherapy].

The development of new chemotherapeutic protocols especially those cisplatin containing regimens, has lead to a dramatic improvement of remission rates in certain cancers. Nausea and vomiting seems to be the most distressing side effect from the patients point of view. A good administration of classical anti-emetic drugs should yield to at least 50% of good protection. The introduction of new drugs should even give more protection to our patients.

Antiemetics↗