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Biomedical subjects

P Alberto

Publications and source records attributed to P Alberto.

At least 19 recordsLinked to original sources
PubMed2001

Isospin asymmetry in the pseudospin dynamical symmetry.

Pseudospin symmetry in nuclei is investigated considering the Dirac equation with a Lorentz structured Woods-Saxon potential. The isospin correlation of the energy splittings of pseudospin partners with the nuclear potential parameters is studied. We show that, in an isotopic chain, the pseudospin symmetry is better realized for neutrons than for protons. This behavior comes from balance effects among the central nuclear potential parameters. In general, we found an isospin asymmetry of the nuclear pseudospin interaction, opposed to the nuclear spin-orbit interaction which is quasi-isospin symmetric.

Journal Article↗
PubMed2000

Emerging potentials for an antioxidant therapy as a new approach to the treatment of systemic sclerosis.

Oxidative stress, favoring disease progression by a rapid degeneration of endothelial cell function is deeply involved in Systemic Sclerosis (SSc) pathogenesis. Raynaud's phenomenon (RP), present in 90% of patients with SSc, provoking frequent daily episodes of hypoxia-reperfusion injury, produces several episodes of free radicals-mediated endothelial derangement. These events results in a positive feedback effect of luminal narrowing and ischemia and therefore to the birth of a vicious cycle of oxygen free radicals (OFR) generation, leading to endothelial damage, intimal thickening and fibrosis. Thus ischemia and reperfusion are two criticals events that may induce oxidative stress and inactivation of antioxidant enzymes. In RP and SSc, a reduced concentration of ascorbic acid, alpha-tocopherol and beta-carotene as well as low values of Selenium have been reported. This antioxidative potential deficiency increases the propensity to oxidative stress. favoring the development of injury mediated by OFR. We reviewed several antioxidant compounds, aiming at their capacity of reverting endothelial dysfunction and damage, scavenging lipid peroxidation and reducing multiple episodes of hypoxia-reperfusion injury. In order to interrupt SSc vicious cycle, we propose a main strategy for SSc treatment by a supplementation of antioxidants and different kind of drugs with antioxidant property, such as Lazaroids, Resveratrol, Melatonin and Probucol.

Antioxidants↗
PubMed2000

Docetaxel (Taxotere)-cisplatin (TC): an effective drug combination in gastric carcinoma. Swiss Group for Clinical Cancer Research (SAKK), and the European Institute of Oncology (EIO).

PURPOSE: A multi-centric trial was performed to explore the clinical activity, in terms of response and toxicity (primary objectives), duration of response and survival (secondary objectives), of docetaxel with cisplatin in advanced gastric cancer (AGC). PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma, performance status < or = 1, normal hematological, hepatic and renal functions and not pretreated for advanced disease by chemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2 dl, cisplatin 75 mg/m2 dl) q3w. Dose escalation to 100 mg/m2 was performed in five patients and was discontinued for excessive toxicity. RESULTS: Forty-eight patients were accrued. A median of 5 cycles/patient was given. We observed 2 complete and 25 partial responses for an overall intent to treat response rate of 56% (95% CI: 41%-71%). Twelve patients had stable disease for > or = 9 weeks (3 cycles). The median time to progression and overall survival were 6.6 and 9 months, respectively. Grade > or = 3 toxicities were neutropenia 81%, anemia 32%, thrombocytopenia 4%, alopecia 36%, fatigue 9%, mucositis 9%, diarrhea 6%, nausea/vomiting 4%, neurologic 2%, and one anaphylaxis precluding treatment administration. We recorded nine episodes of non-fatal febrile neutropenia in eight patients, two of them with docetaxel at 100 mg/m2. There were no direct treatment-related deaths. CONCLUSIONS: TC is active in AGC with a high response rate in a multicentric trial. Despite its hematotoxicity, this regimen is well tolerated and can be recycled as originally planned in 78% of the cases. These results may serve as basis for further developments of docetaxel containing regimens in this disease.

Adenocarcinoma↗
PubMed2000

Intra-arterial chemotherapy in locally advanced or recurrent carcinomas of the penis and anal canal: an active treatment modality with curative potential.

The prognosis of locally advanced or recurrent carcinomas of the penis (PE) and of the anal canal (AC) after conventional treatment is dismal. We report 16 patients (eight with AC carcinomas and eight with PE cancers) treated by intra-arterial (IA) chemotherapy. Fifteen of them were treated for locally advanced or recurrent disease and one in an adjuvant setting. The chemotherapy was administered via a femoral IA catheter with its tip located above the aortic bifurcation, under the inferior mesenteric artery. It consisted of eight push injections, given over a 48-h period, of the following drug combination: cisplatin 8.5 mg m(-2), 5-FU 275 mg m(-2), methotrexate 27.5 mg m(-2), mitomycin C 1.2 mg m(-2), and bleomycin 4 mg m(-2). Leucovorin was given po, 4 x 15 mg day(-1), during the chemotherapy and for 3 days thereafter. A total of 52 cycles of treatment were administered. Of the 15 patients evaluable for response, six obtained a CR (three PE, three AC) and eight a PR. Among the complete responders, four are alive and disease-free 2-15 years after treatment. The other patients enjoyed an objective response lasting 3-25 months (median 7 months). Four patients developed grade III/IV haematological toxicity with three episodes of febrile neutropenia, one of them with a fatal outcome due to patient's failure to obtain medical attention at the onset of his fever, one a grade III mucositis of the glans, and four a grade III/IV cutaneous toxicity, the latter caused by the IA administration of bleomycin. In conclusion, IA chemotherapy is effective and potentially curative in locoregionally advanced or recurrent carcinomas of the penis and of the anus. Its contribution in the primary management of advanced penile or anal carcinoma should be prospectively investigated.

Administration, Oral↗
PubMed2000

Phase II trial of up-front accelerated thoracic radiotherapy combined with chemotherapy and optional up-front prophylactic cranial irradiation in limited small-cell lung cancer. Groupe d'Oncologie Thoracique des Régions Alpines.

PURPOSE: To investigate the feasibility and outcome of bifractionated, up-front thoracic radiotherapy (TR) (45 Gy in 30 fractions of 1.5 Gy twice daily over 3 weeks) combined with chemotherapy (CT) (six cycles of cisplatin and etoposide) and optional low-dose, up-front prophylactic cranial irradiation (18 Gy in 10 fractions of 1.8 Gy twice daily over 5 days) in limited small-cell lung cancer. PATIENTS AND METHODS: CT (etoposide 100 mg/m(2) for 3 days and cisplatin 25 mg/m(2) for 3 days) was started on day 8 or 15 after the first TR treatment. In the five subsequent cycles, cisplatin was given as a single 100-mg/m(2) dose on day 1 every 4 weeks. A total of 52 patients were entered (41 men and 11 women); the median age was 55 years (range, 33 to 67 years). World Health Organization performance status was 0 in 34 patients, 1 in 16 patients, and 2 in two patients. Thirty-six patients (69%) received the full planned six cycles of CT. RESULTS: All treated patients were assessable for response. Thirty-one patients (60%) achieved a complete response, and 16 (30%) had a partial response. One-, 3-, and 4-year survival rates were 74% (95% confidence interval [CI], 60% to 84%), 34% (95% CI, 21% to 49%), and 32% (95 CI, 16% to 46%), respectively. The median survival time was 18 months. Event-free survival at 1 year was 45% (95% CI, 32% to 58%) and at 3 years, 30% (95% CI, 18% to 44%). The main radiation-related acute toxicity was esophageal: 38% of the patients experienced grade 3 or 4 acute toxicity. CT was well tolerated. Although grade 3/4 neutropenia was observed in 86% of the patients, only 4% presented with associated fever. Grade 3/4 nausea and vomiting was seen in 35% of patients. CONCLUSION: This trial demonstrates that up-front accelerated TR associated with CT is feasible, has acceptable toxicity, and shows considerable long-term survival potential.

Adult↗
PubMed1999

Cladribine with cyclophosphamide and prednisone in the management of low-grade lymphoproliferative malignancies.

The feasibility of combining cladribine with cyclophosphamide and prednisone in the management of indolent lymphoid malignancies was determined. Nineteen patients [nine chronic lymphocytic leukaemia (CLL), seven non-Hodgkin's lymphoma (NHL) and three macroglobulinaemia (M))] received cladribine 0.1 mg kg(-1) per day as a subcutaneous bolus injection on days 1-3 (up to 5 injections) with intravenous cyclophosphamide 500 mg m(-2) on day 1 and oral prednisone 40 mg (m-2) on days 1-5 at 4-weekly intervals up to a maximum of six courses. A total of 80 courses were given. Overall response rate was 88%, with four patients achieving a complete clinical and haematological response and 12 achieving a partial response. Neutropenia WHO grade 4 in two patients and WHO grade 3 infection in one patient were the limiting toxicities on treatment. During the follow-up, WHO grade >3 haematological complications occurred in five patients and WHO grade >3 non-haematological complications in five patients. There were no treatment-related deaths. This study demonstrates the feasibility of the cladribine/cyclophosphamide/prednisone (CCP) combination that appears highly active and safe in the management of indolent lymphoid malignancies.

Aged↗
PubMed1999

High dose etretinate and interferon-alpha--a phase I study in squamous cell carcinomas and transitional cell carcinomas.

Simultaneous exposure to retinoids and interferons can result in enhanced antiproliferative and differentiating effects on malignant lesions. We studied the toxicity and the potential efficacy of an association of high dose etretinate and Interferon-alpha (IFN-alpha) in squamous cell carcinomas of the lung, head and neck, the esophagus, cervix and the penis, as well as in transitional carcinomas of the bladder. The treatment consisted of etretinate (Tigason) 4 mg/kg/d on 2, 3, 4 and finally 5 consecutive days every other week and IFN-alpha (Roferon) 6 Mio IU sc. q.d. for 5 days every week. Of 24 patients enrolled, 23 were assessable for toxicity and 20 for response. With two occurrences of grade 3 cutaneous toxicity, the administration of etretinate (Tigason) 4 mg/kg/d on 5 consecutive days every other week and IFN-alpha (Roferon) 6 Mio IU sc. q.d. for 5 days every week was considered to be the MTD. Toxicity was mild otherwise, mostly at grades 1 and 2 level, causing fatigue, skin peeling and erythema, mucositis and cheilitis; 3 PR (partial response) and 8 SD (stable disease) were recorded. Of the responders, one patient had become resistant to cisplatin-based chemotherapy and the other two had at no time ever received systemic therapy. We conclude that the association of high doses of etretinate and IFN-alpha has moderate activity in squamous cell carcinomas, is well tolerated, and that IFN-alpha plays a role in the improved tolerance of the retinoid.

Adult↗
PubMed1998

Alternating radiotherapy and chemotherapy for inoperable Stage III non-small-cell lung cancer: long-term results of two Phase II GOTHA trials. Groupe d'Oncologie Thoracique Alpine.

PURPOSE/OBJECTIVE: To report on two consecutive Phase II cooperative trials in which we evaluated the combination of alternating hyperfractionated accelerated radiotherapy and cisplatin-based chemotherapy in inoperable Stage III non-small cell lung cancer (NSCLC). PATIENTS & METHODS: Between February 1986 and September 1989, 65 patients were entered in the first trial (GOTHA I), and between December 1989 and October 1992 67 were enrolled in the second trial (GOTHA II). In both protocols, radiotherapy (RT) was administered twice daily, at 6 h intervals, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT was given during weeks 2, 3, 6, and 7, over an elapsed time of 6 weeks. In GOTHA I, three cycles of cisplatin, 60 mg/m2 day 1, mitomycin, 8 mg/m2 day 1, and vindesin 3 mg/m2 day 1 and the first day of the following week, were given during weeks 1, 5, and 9; in GOTHA II, cisplatin 70 mg/m2 day 1 and vinblastin 5 mg/m2 day 1 and the first day of the following week were given during weeks 1, 5, 9, 13, 17, and 21. RESULTS: With a minimum follow-up of 3 years, the 1-, 2-, 5-, and 8-year overall survival probability was 56% (95% CI 47-64%), 27% (20-35%), 12% (7-18%) and 9% (3-16%), respectively, with a median survival of 13.6 months (11.4-16.8). Median follow-up for survivors was 6 years (3.3-9.9). There were no survival differences between Stages IIIA and IIIB (p = 0.84), performance status 0, 1, 2 (p = 0.87), sex (p = 0.45) or between the two treatment protocols. At this time, 14 patients are alive, and 118 have died: 102 from NSCLC, 4 from acute toxicity, 2 from secondary surgery, 4 from other medical causes, and 6 from unknown causes. Correlation between response and long-term survival was poor, since of the 24 patients who survived 3 years or more, only 6 (25%) were classified as having a complete response; the remainder having either a partial response (11, 46%), no change (6, 25 %), or "progressive disease" (1, 4 %). First site of relapse was local in 31% of these cases, distant in 43%, local and distant in 15 %, and unknown in 11%. Main grade 3-4 acute toxicities were nausea-vomiting (17%), mucositis (15%), leukopenia (41%), and thrombocytopenia (11%). Eight patients presented with grade 3-4 symptomatic lung radiation pneumopathy. CONCLUSION: Based on this experience with 132 patients, this combination of alternated RT and chemotherapy (CT) for inoperable Stage III NSCLC is feasible with acceptable toxicity, and long-term results suggest a gain in survival when compared to those obtained with conventional RT alone. However, the still high local and distant failure rates indicate that both local and systemic therapies need to be improved.

Adult↗
PubMed1998

Effect of low-dose chest irradiation before chemotherapy on the rate of local failure in small-cell lung cancer.

PURPOSE: To evaluate the rate of tumor recurrence within the irradiated volume after initial low-dose irradiation of limited-stage small-cell lung cancer (SCLC), to assess the tolerance of a sequential combination of low-dose chest irradiation followed by chemotherapy, and to confirm the responsiveness of limited-stage SCLC to low-dose irradiation. METHODS AND MATERIALS: In this pilot study, 26 patients with limited-stage SCLC were treated by first-line 20-Gy thoracic irradiation followed 3 weeks later by chemotherapy (cisplatin, doxorubicin, and etoposide for six cycles). RESULTS: We present our final results with a median follow-up of surviving patients of 7 years. The response rate to this low-dose irradiation was 83%, with an overall response rate to radiochemotherapy of 96% and a median survival of 21 months. No unexpected early or late toxicity was observed. The rate of initial isolated local failure was 8%, which compares favorably with other published series using higher doses of radiochemotherapy. CONCLUSION: An initial chest irradiation of 20 Gy before chemotherapy could be sufficient to reduce the risk of local failure during the time of survival of patients with limited-stage SCLC. Potential advantages of this treatment may be the prevention of resistance mechanisms to radiotherapy induced by preliminary chemotherapy and a reduced radiation-induced toxicity.

Aged↗
PubMed1998

Cisplatin, doxorubicin and etoposide (PAV) in advanced gastric carcinoma: the SAKK experience. Swiss Group for Clinical Cancer Research (SAKK).

EAP (etoposide, doxorubicin, cisplatin), a chemotherapeutic combination given over 8 days, proposed by German investigators in cancer of the stomach, has been considered to be too toxic by others. A positive experience with a similar regimen (PAV) developed by the SAKK given over 3 days in small cell lung cancer led us to test it in gastric adenocarcinoma. 41 patients with metastatic gastric cancer were enrolled in the study and 38 were evaluable for response and toxicity. One complete response and 12 partial responses were recorded, giving a response rate of 34% (95% confidence interval (CI) 20-51%). Median progression-free and overall survival were 3.4 and 6.3 months, respectively. Haematotoxicity was the leading toxicity with 34 (90%) and 17 (45%) grade III-IV neutropenia and thrombocytopenia, respectively. Despite this high rate of granulocytopenia, only six episodes of non-fatal febrile neutropenia were observed. Other toxicities were relatively easy to manage with infrequent grade III-IV occurrences. We conclude that PAV is active in gastric cancer and seems to be better tolerated than EAP.

Adenocarcinoma↗
PubMed1997

Feasibility, toxicity, and activity of LNH84-derived chemotherapy in the management of aggressive lymphomas.

The results of chemotherapy remain unsatisfactory for many patients with advanced lymphomas. Both standard and more aggressive chemotherapy regimens might have their respective role in the management of theses diseases. We have tested the feasibility and assessed the toxicity and activity of a LNH84-derived chemotherapy for aggressive non-Hodgkin's lymphoma in two general hospitals. Thirty-three untreated patients were included over a period of 4 years. Median age was 39 years, 21 were male. International Working Formulation was F for 2 patients, G for 17, H for 8, I for 1, J for 4, one unclassified. Seventeen patients had B symptoms, 15 stage IV, 8 bulky disease, 21 abnormal LDH, 5 performance status > or =2. The overall response rate was 93%. The single treatment related death resulted from bleomycin acute pneumonitis. Neutropenia WHO grade 4 occurred in all patients, resulting in infections grade 3 in 12 and thrombocytopenia grade 4 in 3. In the induction phase, courses could never be repeated day 14. The dose intensity of the four drugs contained in this phase is thus calculated between 64.5 and 81.5%. At 3 years, overall survival is 80% and event-free survival is 62%. This LNH84-derived regimen is effective. However, the induction phase is toxic and a 3-weekly interval appears more appropriate. Such intensive treatment might benefit patients with very aggressive lymphomas and this should be studied in randomized comparison against standard CHOP.

Adolescent↗
PubMed1997

A double-blind crossover study comparing prophylactic intravenous granisetron alone or in combination with dexamethasone as antiemetic treatment in controlling nausea and vomiting associated with chemotherapy.

The efficacies of granisetron plus dexamethasone and granisetron alone in controlling nausea and vomiting during two consecutive cycles of moderately emetogenic chemotherapy given for up to 5 days were compared in a two-centre, randomised, double-blind, placebo-controlled crossover study. In all, 110 evaluable patients received either dexamethasone, 20 mg i.v., or matching placebo, plus open-label granisetron, 3 mg i.v., given on each chemotherapy day. At cycle 2, patients crossed over to the alternative treatment; 72 patients completed the crossover. In these 72 patients, the complete response rates over 24 h for granisetron plus dexamethasone and granisetron plus placebo in cycle 1 were 87% and 70% (ns), respectively. In cycle 2 the complete response rates over 24 h were 73% and 62% (ns). Combining the two cycles, the complete response rates over 24 h were 80.6% (granisetron plus dexamethasone) and 65.3% (granisetron plus placebo; P = 0.015). Granisetron plus dexamethasone was significantly more effective in terms of times to less than complete response (P = 0.041), to first episode of moderate/severe nausea (P = 0.04), to first episode of vomiting (0.03) and to use of rescue medication (P = 0.02). Adverse events tended to be minor, with asthenia and insomnia the most common. Of those patients who expressed a preference, 67% preferred granisetron plus dexamethasone (P < 0.05). A single dose of dexamethasone added to granisetron thus enhances the efficacy of granisetron alone in preventing nausea and vomiting after moderately emetogenic chemotherapy.

Adolescent↗
PubMed1996

[Chemotherapy of gastrointestinal carcinomas and non-small-cell pulmonary carcinoma: a controversy].

Patients with metastatic gastrointestinal cancers and metastatic non-small cell lung cancer present an important challenge in medical oncology and palliative care. Symptoms caused by tumor progression should undoubtedly be treated. The management of asymptomatic patients, however, is still controversial. A clinical decision on whether an asymptomatic patient should be treated with chemotherapy at an early or at a late stage in the evolution of the disease must often be reached on an individual basis. Ongoing clinical research to improve treatment results is still urgently needed. Research programs should aim at (a) evaluating new drugs and (b) testing new multi-modal treatment strategies.

Antineoplastic Agents↗
PubMed1996

Initial prognostic factors in small-cell lung cancer patients predicting quality of life during chemotherapy. Swiss Group for Clinical Cancer Research (SAKK).

The question of whether initial prognostic factors in small-cell lung cancer patients have a predictive value for patients' quality of life (QL) during chemotherapy is addressed in the context of a randomised clinical trial comparing early and late alternating chemotherapy (SAKK protocol 15/84). The relative impact of initial tumour stage and performance status, previous weight loss, sex and age on patient-rated QL was analysed over six chemotherapy cycles in 124-130 patients (according to available QL data) with more than 400 questionnaires. Fatigue/malaise, personal functioning, emotional and general well-being were prospectively selected as QL indicators. Predefined summary measures (average QL score over chemotherapy cycles, 'minimum', 'maximum' and 'final' improvement) were analysed separately by scale in various patient groups. General linear models adjusted for treatment arm and response were used to confirm the univariate findings. Within the overall sample, the average QL scores over six cycles were predicted by initial prognostic factors. Patients with poor prognostic factors reported worse QL. Within a limited sample (with baseline QL), patients with poor prognostic factors reported worse QL at baseline and greater improvement under treatment. Graphical comparison of QL patterns over cycles showed permanent discrimination by levels of prognostic factors. The impact of initial prognostic factors was consistently confirmed in the three analyses. Levels of performance status and weight loss best discriminated QL. Initial tumour stage, performance status and previous weight loss can predict QL in small-cell lung cancer during chemotherapy, even after controlling for response to treatment. Our results may contribute to clinical decision-making with regard to the intensity of chemotherapy and QL outcome, especially in patients with extensive disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Treatment of aggressive non Hodgkin's lymphoma: the experience of a general hospital].

PURPOSE: The LNH84 regimen for aggressive non Hodgkin's lymphoma consists in an intensive induction phase followed by a consolidation phase. The objectives of this study are to evaluate the feasability and activity of a modified induction phase of this regimen in an oncologic department of a general university hospital. PATIENTS: Twenty-eight consecutive patients receive three or four induction courses of CDBVP corresponding to intravenous cyclophosphamide (C), doxorubicin (D), bleomycin (B), vincristine (V) and oral prednisone (P), for a total of 89 courses. Median age is 42 years and 18 patients are male. IWF is F to J. Fourteen have B symptoms, five a bulky disease, 18 abnormal LDH and nine bone marrow involvement. RESULTS: After the induction phase, 12 patients achieve CR and 11 PR for an overall response rate of 92%. Toxicity consists in severe myelosuppression with a neutropenia WHO grade 4 in all patients. The interval between courses is lengthened for each period, with a median interval of 18.5 days between cycle 1 and 2, 19.5 days between cycle 2 and 3 and 22 days between cycle 3 and 4. Eight patients present an infection WHO grade 3 and one patient died of a treatment related pulmonary complication. At 3 years the overall survival and event free survival is 78% and 57% respectively. CONCLUSIONS: In our experience, the CDBVP protocole is a toxic regimen difficult to administer in a general hospital. Its administration out of a protocole can not be recommanded for good prognosis patients. Its interest for poor prognosis patients should be evaluated with clinical studies.

Adolescent↗