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Biomedical subjects

P Fournel

Publications and source records attributed to P Fournel.

At least 19 recordsLinked to original sources
PubMed1998

Microsatellite instability and loss of heterozygosity at chromosomes 9 and 17 in non-small cell lung cancer.

BACKGROUND: Microsatellite instability (MI) and loss of heterozygosity (LOH) are described in lung cancer specimens. However, their importance in tumorigenesis remains unknown. The aim of this study was to identify the presence of MI and LOH in human tumor and normal bronchial mucosa DNA. METHODS: We performed biopsies with fiberoptic bronchoscopy and took specimens from the tumor and from the opposite site normal bronchial mucosa in 20 patients with non-small-cell lung cancer (NSCLC). Four patients had an adenocarcinoma, while 16 had a squamous cell carcinoma. Also, 6 patients had an early-stage disease (stages I and II), while 14 patients had an advanced-stage disease (stages III and IV). All paired specimens were studied for MI and LOH on chromosome 17p, 17q, 9p, and 9q, with 10 polymorphic markers. RESULTS: Sixteen of 20 tumors displayed genetic alterations (80%). Six tumors (30%) exhibited MI, five tumors (25%) exhibited LOH, while five tumors exhibited MI and LOH concurrently. The marker HBX had the most frequent incidence of LOH (4/20, 20%), indicating that the hbx gene becomes a strong candidate tumor suppressor gene, whereas of MI it was D17S515 (4/20, 20%). No relationship was observed between the presence of LOH or MI and the histologic subtype of NSCLC or the stage of the disease. CONCLUSION: Results suggest that genetic alterations exist in tumor, compared with the normal mucosa DNA. They may have a role in carcinogenesis as they exist in all stages and in both NSCLC histologic subtypes studied.

Adenocarcinoma↗
PubMed1997

Long-term survivors of small-cell lung cancer (SCLC): a French multicenter study. Groupe d'Oncologie de Langue Française.

BACKGROUND: The aim of this study was to analyze SCLC patients beyond 30 months, particularly their outcome, their way of life, and factors which could influence relapses, second-primary cancers and death. PATIENTS AND METHODS: Between January 1986 and May 1995, 263 SCLC patients who survived longer than 30 months were included from 52 French institutions. The analysis was performed on the 155 cases confirmed by a pathologic review. RESULTS: Physical, mental and psychological states were considered as normal at 30 months in respectively 70.3%, 87.7% and 67.7% of patients, not influenced by prophylactic cranial irradiation, number of chemotherapy cycles, CCNU or cisplatin. Therapeutic sequelae were neurological impairment (13%), pulmonary fibrosis (18%) and cardiac disorders (11%) at 30 months. Return to work was possible for 40% of patients in the first two years following diagnosis. Among 43 relapsing patients, 33 benefited from a second-line treatment. Their median survival was 12 months since retreatment, and seven patients have survived again longer than 30 months. Age > 60 at the time of diagnosis was found as an independent factor increasing the risk of relapse beyond 30 months (OR = 2.46, IC 95% (1.16-5.26), P = 0.01). The risk of relapse became less than 10% beyond five years. Twenty patients (13%) developed a second primary cancer in a mean time of 58.6 months. The risk of second primary cancer was increased by a number of chemotherapy cycles > 6 (OR = 3.25, IC 95% (1.08-9.8) P = 0.02) and by an age > 60 (OR = 2.92, IC 95% (1.07-7.97), P = 0.03). Five- and 10-year survival rates were respectively 68% and 44%. In these patients having reached a 30-month survival, three independent factors were predictive of a survival longer than five years: age < or = 60 at the time of diagnosis (OR = 2.85, IC 95% (1.23-6.6), P = 0.01), chest radiotherapy (OR = 3.1, IC 95% (1.28-7.69), P = 0.006) and absence of relapse (OR = 4.5, IC 95% (1.75-12.5), P = 0.002). This study suggests that: 1) therapeutic sequelae are rather mild, allowing return to work in 40% of patients; 2) relapsing 30-month survivors can benefit from second-line treatment; 3) SCLC cure can be achieved with a 10-year follow-up.

Adult↗
PubMed1997

[An unusual cause of aorto-bronchial fistula: tuberculosis aortitis].

The aortic rupture in the pulmonary parenchyma or the bronchi rarely results in an haemoptysis. It means in most of the cases the rupture of an aortica aneurysm. We relate the observation of a aorto-bronchial fistula from a tuberculosa origin in an old woman case. Although the tuberculosa aortitis is becoming very exceptional, it still remains the cause of aorta rupture, with the formation of a false aneurysm which is rapidly fatal and so, it is important to search for it before any capricious haemoptysis.

Aged↗
PubMed1997

[Spontaneous chylothorax. Apropos of a further case].

The authors describe a case of spontaneous chylothorax occurring in a 50-year-old woman after stretching exercises of the upper limbs. A positive diagnosis was made based on pleural aspirate and a biochemical study of the pleural liquid (triglycerides > 3 gm/l). The chylothorax is said to be spontaneous when detailed investigations are negative. The outcome was satisfactory with complete regression of the symptoms after pleural aspirate and a low diet in long chain triglycerides but the authors recall that treatment may be surgical in cases of multiple recurrence.

Chylothorax↗
PubMed1996

Cisplatin and ifosfamide with various doses of vinorelbine (navelbine) in advanced non-small lung cancer.

From November 1992 to March 1994 we concluded a phase II trial of the combination of cisplatin 75 mg/m2 and ifosfamide 3 g/m2 on day 1 and increasing doses of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France). Group A was given vinorelbine 25 mg/m2 on day 1, group B 25 mg/m2 on days 1 and 8, and group C 25 mg/m2 on days 1 and 15 and 12.5 mg/m2 on day 8. Inclusion criteria were histologically proven non-small cell lung cancer, stage IIIB or IV disease, no underlying disease, performance status < 2, no previous chemotherapy or radiotherapy, not older than 75 years, and informed consent. Treatment was given for 3 weeks. Eighty-six patients were included: 34 in group A, 28 in group B, and 24 in group C. One patient in group B was excluded because of false histology on review. Thirty-seven patients had stage IIIB and 48 had state IV disease, and 37 had squamous cell carcinoma, 32 had adenocarcinoma, and 16 had large cell carcinoma. The median age was 59.2 years (age range, 36 to 73 years). Evaluation was made 3 weeks after the third course of therapy. Thoracic radiotherapy (60 Gy) was given in stage IIIB disease; in stage IV disease, when an objective response was achieved, three additional courses of chemotherapy were given. The response rate after three cycles was 32% in group A, 44% in group B, and 67% in group C. Dose intensity, using Hryniuk's method, was the same for cisplatin and ifosfamide in the three groups. Dose intensity for vinorelbine was 8.1 mg/m2/wk in group A, 14.7 mg/m2/wk in group B, and 16.9 mg/m2/wk in group C. This study shows that increased dose intensity with vinorelbine is feasible and seems to increase the response rate and median survival, which was 28 weeks in group A and 38 weeks in group B. Median survival had not been reached in group C.

Adenocarcinoma↗
PubMed1996

[Mediastinal adenopathies metastatic from a basocellular skin carcinoma].

Skin basocellular carcinoma is very frequent, and does not usually cause distant metastasis. However, a few cases of distal lymph node, pulmonary, bone metastasis have been described in the literature. In the present case, we report a basocellular mediastinal lymph node metastasis. Some precise histological characteristics described by Lattses must be present to admit authenticity of these metastasis. The treatment of such cases is based on surgery, radiotherapy and chemotherapy containing cisplatinum. However, the overall prognosis of these metastases remains poor.

Biopsy↗
PubMed1995

Limbic encephalitis and immunological perturbations in two patients with thymoma.

Two patients with clinical and radiological evidence of limbic encephalitis associated with an invasive lymphoepithelial thymoma who improved after thymectomy and radiotherapy are reported. The serum of both patients and the CSF of one of them contained different types of antibodies that immunoreacted with human and rat brain and newborn rat thymus. After treatment of the tumour, the antibody titres decreased. Similar antibodies were not found in various controls. Two out of 16 patients with thymoma, myasthenia gravis, and no CNS involvement had low titres of antibodies reacting with the brain. It is suggested that in some patients with thymoma, an autoimmune reaction involving antigens common to the brain and thymus is possibly misdirected against the CNS.

Aged↗
PubMed1995

[Study of chemosensitivity in patients believed to have sleep apnea syndrome].

We performed polysomnography and measured hypoxic ventilatory (HVR), hypercapnic ventilatory responses (HCVR) in 42 patients (60 +/- 11 years) with obesity and a clinical suspicion of sleep apnea syndrome (SAS) in order to determine whether an altered chemosensitivity was associated with SAS. The apnea/hypopnea index was 38 +/- 20 events per hour of sleep in 28 patients (SAS+ group) and less than 10 in the 14 others (SAS- group). The 2 groups differed only by a lower waking PaO2 in SAS+ as compared to SAS- (71.0 +/- 9 vs 77.4 +/- 8 mmHg, p < 0.05). HVR and HCVR were not significantly different in the 2 groups (0.82 +/- 0.58 vs 0.86 +/- 0.37 l.min-1.%-1; 1.41 +/- 0.81 vs 1.40 +/- 0.67 l.min-1.mmHg-1, respectively). In SAS+ group, HVR or HCVR did not change 3 or 12 months after continuous positive airway pressure (CPAP) therapy while both polysomnography and PaO2 returned to normal. We conclude that in patients with mild obesity and SAS there is no difference in chemosensitivity due to the presence of sleep apnea and that CPAP therapy does not alter these measurements. These results suggest no direct effect of SAS on chemosensitivity in the population studied.

Aged↗
PubMed1995

Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? The French Navoban Study Group.

The purpose of this study was to evaluate and compare the antiemetic effectiveness and tolerability of Navoban (tropisetron) and Zofran (ondansetron) following high-dose (> or = 50 mg/m2) cisplatin chemotherapy. In a randomised, multi-centre, double-blind, double-dummy, parallel group study, 117 evaluable chemotherapy-naive patients who received Navoban were compared with 114 who received Zofran. Patient diary cards were used to assess both acute (Day 1) and delayed (Days 2-6) nausea and vomiting. Total control of acute vomiting was achieved in 54% of Navoban and 65% of Zofran patients (p = 0.052), and total control of acute nausea in 66% and 62% respectively (p = 0.655). Total control of delayed vomiting was achieved in 44% of Navoban patients and 46% of Zofran patients (p = 0.765), and of delayed nausea in 56% and 47% respectively (p = 0.207). Both reactions combined were totally prevented during the entire 6-day trial period in 22% of Navoban and 24% of Zofran patients (NS), while a further 42% of patients in both groups remained largely free from both nausea and emesis. The few adverse reactions (e.g. headache, constipation, diarrhoea) were mainly mild and typical of the 5-HT3-receptor antagonists. In conclusion, there were no significant differences in efficacy and tolerability between Navoban 5 mg once daily and the highest recommended dose of Zofran (32 mg on Day 1, followed by 8 mg three times a day).

Antiemetics↗
PubMed1994

[Delayed detection of cystic fibrosis in a patient with Mycobacterium avium complex infection].

We report a case of pulmonary infection by Mycobacterium avium complex revealing in a 21 years old patient a cystic fibrosis heterozygous for the delta F 508 deletion. The role of this bacteria in the lung infection is suggested by repeated isolation. This infection caused bronchitis, hypoxemia and pulmonary nodules at CT scan. The clinical and radiological signs improved after treatment with four antibiotics whereas only clarithromycin showed in vitro activity. An obstructive disease due to allergic bronchopulmonary aspergillosis developed and was controlled by steroid therapy.

Adult↗
PubMed1993

Limited disease small cell lung cancer: alternating combination of doxorubicin, etoposide, ifosfamide and hyperfractionated radiotherapy. Final results of a multicentric pilot study for the Groupe Lyonnias d'Oncologie Thoracique (GLOT).

In order to evaluate the effect on prolonging survival of alternating chemotherapy and radiotherapy schedules in patients with limited disease small cell lung cancer, 89 patients were included in a multi-institutional pilot study between January 1986 and May 1989. Treatment consisted of induction chemotherapy using the combination of doxorubicin, etoposide and ifosfamide (AVI) for four consecutive courses, followed by two cycles of the VI chemotherapy alternating with three hyperfractionated radiotherapy courses and then followed by two additional courses of AVI. Objective response to the four cycles of AVI combination was observed in 65 patients (75%). Thirteen out of 30 patients (44%) who were in partial response (PR) after induction chemotherapy were converted into complete response (CR) after the three alternating courses of chemotherapy and radiotherapy. The principal side effect related to combined modality treatment was acute radiation pneumonitis (21.5% cases) reversible except one which resulted in toxic death, and a second with chronic lung fibrosis with permanent WHO Grade 2 dyspnea (14%). Local relapse was observed in 47% of the patients who were considered in CR at the end of the treatment program and cerebral metastases were the first site of detectable relapse in 25% cases. The 3-year actuarial disease-free survival of the 89 patients is 5%, and the median actuarial survival is 14 months. This study shows that the promising survival rates seen in our previously published interim analysis were not maintained. Reasons for this might include the choice of a non cisplatinum containing induction chemotherapy, the late introduction of thoracic irradiation and/or to the use of non-restrictive criteria for selecting patients.

Adult↗
PubMed1993

[Results of a combination of platinum-vindesin-ametycin-bleomycin (CEMB) in the treatment of stage IV non-small-cell lung cancers].

From July 1987 to July 1988, 35 patients with non small cell lung cancer, stage IV, were included in a phase II trial (GLOT NPC 87/01). The treatment was as follows: cisplatin 50 mg/m2 day 1, vindesin 3 mg/m2 day 1, mitomycin 6 mg/m2 day 2, and bleomycin 15 mg/day, day 1 + 2 by continuous infusion. The evaluation for response was assessed after three courses of chemotherapy. The results were poor: an objective response was observed in three patients: three partial responses and no complete response. Because of tumor progression (18 patients) or toxicity (three patients), 21 patients did not complete the three cycles of chemotherapy. The median survival rate was 100 days. Toxicity was mild: grade III neutropenia occurred in one patient, grade IV thrombocytopenia was also observed in one patient. We conclude that this treatment has only a poor efficacy in stage IV non small cell lung cancer.

Adenocarcinoma↗
PubMed1992

Initial combined cryotherapy and irradiation for unresectable non-small cell lung cancer. Preliminary results.

In unresectable non-small cell lung cancer (NSCLC) with a patent mainstem bronchus, some studies of obstructive tumors, showed (1) a poor role for irradiation in obtaining efficient debulking and (2) an interest in preliminary laser treatment in these patients. Cryotherapy is another method to obtain debulking. Moreover, several studies showed that cryotherapy would increase the radiosensitivity of a tumor. We performed a preliminary protocol combining successively initial cryotherapy followed by irradiation in inoperable NSCLC (either for local or functional contraindications). Thirty-eight patients were included and treated first by cryotherapy performed under general anesthesia and then with external irradiation in a curative intent. The efficiency of cryotherapy assessed on bronchoscopy was found to be volume-efficient (VE) in 26 of the 38 patients and non-volume-efficient (NVE) in the other 12 patients. After irradiation in the VE group, 17 of the 26 patients had no bronchial residual tumor (NRT). In contrast, all of the patients in the NVE group had a bronchial residual tumor (RT). Survival in the VE group (median, 397 days) was significantly higher than the survival of the NVE group (median, 144 days). Survival was found to be independent of the surgical contraindication (local or functional). The best survival was associated both with the efficiency of the initial debulking (VE) by cryotherapy and with the local control (NRT) induced by the irradiation (median, 560 days). Local control was obtained in 65 percent (17/26) of the cases in the VE group and was never observed in the NVE group. In our study the VE group's local control is better than the 35 percent usually reported after irradiation alone. These results argue for the efficient potentiation of irradiation by cryotherapy.

Adult↗
PubMed1992

[Comparison of 2 cisplatin and etoposide dosages in relapsing small cell lung cancer].

The synergistic combination of cisplatinum and etoposide appears as the best second line treatment in patients relapsing from small cell lung carcinoma (SCLC). In order to test the dose-effect relationship of cisplatinum and etoposide in this situation, we have performed a randomised phase II trial comparing 2 five-day regimens: cisplatinum 20 mg/m2/day+etoposide 60 mg/m2/day (arm A) versus cisplatinum 40 mg/m2/day+etoposide 100 mg/m2/day (arm B) every 4 weeks. Thirty-seven patients were included (arm A: 18, arm B: 19), and 32 were considered to be eligible (arm A: 15, arm B: 17). Eight patients were non evaluable, five of them because of toxic death occurring prior to the second course (arm A: one from neutropenia; arm B: three from neutropenia and one from thrombopenia). The two groups were well balanced with regard to the main prognostic factors (age, sex, performance status, LDH level, response to induction chemotherapy). An objective response was observed in 10/24 evaluable patients (arm A: 4, arm B: 6) and was considered as complete in one patient in arm A and in 2 pts in arm B; these two patients presented with cerebral metastases and their response lasted 9 and 15 weeks respectively. The mean duration of response was 11 weeks in arm A and 10.5 weeks in arm B. The median actuarial survival of the overall population of eligible patients was 15 weeks: 13 weeks in arm A and 16.5 weeks in arm B. The study was discontinued because of the 23.5% toxic deaths rate in the high doses arm in this heavily pre-treated population of patients. However, the high response rate (54% overall, 35% considering toxic death as a failure) is impressive and presents evidence for the dose/effect relationship in SCLC.

Aged↗
PubMed1990

Hyperfractionated radiotherapy alternating with multidrug chemotherapy in the treatment of limited small cell lung cancer (SCLC). Groupe Lyonnais d'Oncologie Thoracique.

From January 1986 through December 1988, 227 patients were included in a multi-institutional pilot study for small cell lung cancer (SCLC). Out of the 211 patients who fully completed the staging procedures, 77 (35%) appeared to have SCLC limited to the thorax. All patients received combination therapy consisting of AVI (Adriamycin, VP-16 and Ifosfamide), except during radiotherapy when the Adriamycin was omitted, plus twice daily fractionated 18 MV radiotherapy. Treatment protocol consisted of 4 initial courses of AVI, followed by 3 courses of radiotherapy alternating with modified chemotherapy (VP-16 and Ifosfamide), completed by 2 courses of initial chemotherapy (AVI). Radiotherapy consisted of 1.5 Gy/fraction, 2 fractions/day, 5 days/week in the first course, and 1.8 Gy/fraction, 2 fractions/day, 5 days/week, in the second and third courses, for a total tumor dose of 51 Gy, felt to be equivalent to 60 Gy at normal fractionation. CT treatment planning was employed to design a treatment consisting of multiport radiotherapy, using AP-PA and laterals or obliques beams. During the first course, the homolateral hemithorax received 9 Gy total dose on days 1, 3, 5. During the third course, 360 degrees arctherapy was generally used to boost the reduced tumor volume to a 51 Gy. Besides chest X ray and CT scan, staging and restaging procedures included fiberoptic bronchoscopy. Response rate after irradiation is 61%, with 46% complete responders and 51% local control. The median survival is 14 months, and disease-free survival 42% at 1 year. Complications consisted of cardiac toxicity in 2 patients, 1 death of acute pulmonary toxicity, and 4 instances of moderate chronic radiation pneumonitis. Thus, high doses of radiation can be delivered combined with chemotherapy using this protocol, with an acceptable toxicity and encouraging results in response rate and local control. A longer follow-up is needed to evaluate the impact of these results on survival.

Adult↗