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Biomedical subjects

P Alberto

Publications and source records attributed to P Alberto.

At least 37 records · Page 2Linked to original sources
PubMed1995

Rapidly alternating combination of cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy in split course for stage IIIA and stage IIIB non-small cell lung cancer: results of a phase I-II study by the GOTHA group. Group d'Oncologie Thoracique des Régions Alpines.

The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. 65 patients received 3 cycles of cisplatin 60 mg/m2 and mitomycin C 8 mg/m2 on day 1, and vindesin 3 mg/m2 on days 1 and 8 in weeks 1-2, 5-6 and 9-10, alternating with AHRT, 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2-3 (30 Gy) and weeks 6-7 (33 Gy). The dose actually delivered was > 98% for RT, and 85-100% for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary resections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields. Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outside (34) than within (21) radiation fields. The median survival was 15.7 months and the 5 year survival rate was 15% (95% CI = 6-26%). 1 patient died of bladder cancer and another of myocardial infarction. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy.

Adult↗
PubMed1995

Quality versus quantity of life in the treatment of patients with advanced small-cell lung cancer? A randomized phase III comparison of weekly carboplatin and teniposide versus cisplatin, adriamycin, etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: Based on a promising pilot study with weekly carboplatin and teniposide (CBDCA/VM) the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with extensive-disease small-cell lung cancer aimed at the development of an effective palliative treatment with low subjective toxicity. PATIENTS AND METHODS: From September 1989 to September 1991 patients were randomised to a weekly regimen of CBDCA/VM or to our 'standard chemotherapy' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine (PAV-CyMOC). RESULTS: The trial was closed before the planned accrual of 140 evaluable patients due to a significant survival difference shown by an interim analysis. Of the 61 patients 59 were eligible and included in the final analysis. The results achieved with the PAV-CyMOC regimen were significantly better than those observed in patients treated with weekly CBDCA/VM (remission rate of 65% vs. 29%; p = 0.006). The median survival of patients treated with the PAV-CyMOC combination was significantly longer than that of patients receiving weekly CBDCA/VM (260 days vs. 147 days; p = 0.0035). The 1-year survival rate was 30% in the PAV-CyMOC arm compared to 4% in the CBDCA/VM-treated patients. As expected, side effects including myelosuppression, alopecia and mucositis were significantly more pronounced in patients treated with the PAV-CyMOC regimen. No significant difference was found in patient-rated tumor symptoms and general quality-of-life categories. CONCLUSION: Contrary to our initial expectation that we would achieve similar therapeutic results with less subjective toxicity, in this randomised prospective trial the results achieved by weekly carboplatin and teniposide were significantly inferior in terms of remission rate and survival to those of our 'standard regimen' of cisplatin, adriamycin and etoposide alternating with cyclophosphamide, methotrexate, vincristine and lomustine. The weekly regimen was less toxic than the standard chemotherapy. Whether patients are willing to accept a significant trade-off between quantity and quality of life remains to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Transfusion-associated graft-versus-host disease in a patient treated with Cladribine (2-chlorodeoxyadenosine): demonstration of exogenous DNA in various tissue extracts by PCR analysis.

Transfusion-associated graft-versus-host disease can occur in both immunocompetent and immunocompromised hosts. Cladribine is a synthetic analogue of adenine used in the treatment of lymphoid malignancies, commonly associated with a decrease in T lymphocytes. Cladribine was given for a low-grade non-Hodgkin's lymphoma with thrombocytopenia as the main side-effect. Six units of pooled non-irradiated platelets were transfused from six unrelated donors; 10 d later a clinical picture typical of graft-versus-host disease resulted. Polymerase chain reaction of the highly polymorphic DNA minisatellites and HLA-DR oligotyping were used to demonstrate the exogenous DNA. In the patient's blood and tissues, only the pattern of donor 5 was found. The patient (DRB1*0301/1101; DRB3*0101/02) and this donor (DRB1*0301/1104; DRB3*02) by chance shared a partial common haplotype. This complication highlights the sensitivity of DNA minisatellite analysis. It further raises the question of transfusion and of prophylactic irradiation of all blood products in immunosuppressed patients and those treated with cladribine. This case represents a previously unreported situation where an immunosuppressed patient was able to eliminate cells from five totally HLA-DR dissimilar donors but not from one heterozygous donor with strong HLA-DR similarity.

Aged↗
PubMed1995

Human recombinant IL-4 decreases the emergence of non-specific cytolytic cells and favours the appearance of memory cells (CD4+CD45RO+) in the IL-2-driven development of cytotoxic T lymphocytes against autologous ovarian tumour cells.

As IL-4 and IL-6 have also been reported to promote the development of T lymphocytes such as IL-2, we investigated their role in the development of specific cytotoxic T lymphocytes (CTL) against autologous ovarian tumours in mixed lymphocyte tumour cultures (MLTC). Peripheral blood lymphocytes (PBL) from five ovarian carcinoma (OC) patients were incubated with autologous OC cells at a PBL:OC cell ratio of 20:1 in IL-2 alone (50 U/ml for the first week and 200 U/ml thereafter) or with IL-4 (100 U/ml) and/or IL-6 (5 U/ml). Neither IL-4 nor IL-6 improved lymphocyte proliferation consistently. In contrast, IL-4 reduced significantly the development of LAK activity as assayed against Daudi cell line, and decreased modestly the emergence of natural killer (NK) activity as assayed against K562. This property was not shared by IL-6. The prevention of the development of non-specific cytolytic activity (LAK and NK activities) was much stronger when the MLTC was started with IL-4 in the absence of IL-2 during the first week in culture. A concomitant drop in NKH-1 expression (CD56) was observed. By inhibiting the emergence of non-specific cytotoxicity, IL-4 provided better evidence of the specific cytolytic activity directed at ovarian cells. In parallel, a significant increase in the generation of memory cells (CD4+CD45RO+) was observed with IL-4. In conclusion, in this model, IL-4 added before IL-2 decreases significantly the emergence of non-specific cytotoxic cells, and promotes the generation of memory cells. These properties may be of interest in the design of strategies aimed at obtaining tumour-specific cells for investigational and immunotherapeutic purposes.

CD4 Antigens↗
PubMed1995

[Dose intensity in cancer chemotherapy: definition, average relative dose intensity and effective dose intensity].

The cytotoxic activity of cancer chemotherapy is related to the dose and to the amount of drug delivered per time unit. The significance of time in the effectiveness of a treatment program is frequently overlooked. The term of dose intensity (DI) is used to define the drug dose delivered per time unit and is expressed as mg/m2 per week. A delay in the sequence of treatment cycles decreases the DI in the same proportion as a reduction of dose. Average relative DI corresponds to the mean DI of combined agents and is expressed as a fraction of a similar combination selected as a standard. DI is useful to compare the dose actually received with the prescribed dose. The relation of DI with tumor response or survival has not been fully demonstrated. A threshold DI level for therapeutic activity is evident. Above this threshold, a linear relationship of DI and effectiveness is not obvious, particularly regarding high-dose chemotherapy. The term of DI is more useful in its principle than in the significance of its calculated value.

Animals↗
PubMed1995

Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus.

BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.

Adult↗
PubMed1994

Combined-modality treatment of small-cell lung cancer: randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: From 1980 to 1983 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with small-cell lung cancer with the objective of improving the results of induction chemotherapy and defining the role of consolidating chest irradiation. PATIENTS AND METHODS: Patients were initially randomised to induction arms AVP (adriamycin, etoposide and cisplatin given every four weeks for four cycles), EVA (cyclophosphamide, etoposide and adriamycin given every four weeks for four cycles) or MOC/AVP (methotrexate, vincristine, cyclophosphamide alternating with adriamycin, etoposide and cisplatin given for two cycles). All patients received prophylactic cranial irradiation with 30 Gy, and after four months of induction chemotherapy were randomized to maintenance chemotherapy with or without consolidating chest irradiation. The patients in the combined-modality maintenance arm first received radiation therapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. RESULTS: 266 patients were eligible and evaluable. An overall response rate of 70% with 21% of complete remissions, a median survival of 9.3 months and survival of 8% of the patients at two years were observed. The highest objective response rate was achieved with the AVP-induction chemotherapy with an 80% response rate and 32% complete remissions. Similar results were achieved with the alternating regimen of MOC/AVP. In contrast, patients treated with the EVA induction regimen had significantly lower overall remission (56%) and complete remission rates (7%). The role of consolidating chest irradiation could not be clarified in limited-disease patients due to the small number of them who were randomised to the maintenance part of the study. However, in patients with extensive disease in partial remission after induction treatment, combined maintenance therapy had a more significant adverse effect on survival than maintenance chemotherapy alone (median survival in the maintenance phase of 148 days versus 239 days, p = 0.011). CONCLUSION: We conclude that the combination of adriamycin, etoposide and cisplatin is an active induction treatment. Consolidating chest irradiation is contraindicated in patients with extensive disease in partial remission after induction when given in a sequential manner, as in our trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Weekly carboplatin and VM-26 for elderly patients with small-cell lung cancer.

BACKGROUND: Elderly patients are excluded from chemotherapy trials, even though they represent 25% of those with small cell lung cancer. An effective chemotherapy regimen with limited toxicity should be developed with the aim not only of increasing the survival of these patients, but also of improving their quality of life and their independence. PATIENTS AND METHODS: Twenty-four patients with a median age of 72 years and small-cell lung cancer (SCLC) were included in the trial. Chemotherapy consisted of a weekly intravenous regimen of Carboplatin 80 mg/m2 and Teniposide 80 mg/m2 administered on an outpatient basis. RESULTS: Eight patients had limited and 16 extensive disease. After a median of 12 chemotherapy courses (2-31) the overall response rate was 66.7% (95% Cl: 44.7-84.4), with 5 patients in complete and 11 in partial remission. The median overall survival was 33 weeks, with 4 patients alive at more than one year. Improvement of symptoms occurred in 86% of patients. Toxicity, mainly hematological, was moderate. CONCLUSIONS: Weekly Carboplatin and VM-26 is an effective and non-toxic regimen for elderly patients, leading to results similar to those obtained with a more intensive regimen in a younger age group.

Aged↗
PubMed1993

"Fatigue and malaise" as a quality-of-life indicator in small-cell lung cancer patients. The Swiss Group for Clinical Cancer Research (SAKK)

"Fatigue and malaise" (FM) is a frequent, non-specific symptom of cancer patients caused by the disease, its treatment and psychological distress. Since comprehensive quality of life assessment is often not feasible in multicentre clinical trials, short, but clinically relevant, quality of life indicators have to be defined. In a representative subsample of 127 patients in a phase-III randomized small-cell lung cancer trial comparing two different regimens of combination chemotherapy, quality of life was assessed at the beginning of each of the six treatment cycles with a self-rating questionnaire including an early version of the EORTC questionnaire, a mood adjective check list (Bf-S) and a single linear-analogue self-assessment scale (LASA) measuring general well-being. FM, measured with a five-item Likert subscale of the EORTC questionnaire, showed moderate to high intercorrelations with other EORTC subscales assessing disease symptoms, toxicity of treatment, role functioning, personal functioning, restriction of social activity, psychological distress, emotional (Bf-S) and general well-being (LASA). At baseline, FM was one of the most pronounced symptoms. Over the six cycles 43%-31% of the patients complained of moderate to severe fatigue. Over the first two cycles FM tended to decrease, slightly increasing during cycles 3 and 4 and decreasing again before cycle 6. In a multiple regression analysis over the six cycles, 53% of the variance of FM was explained by patient-rated symptoms of disease and toxicity (disease alone: 43%; toxicity alone: 35%). Initial performance status, previous weight loss, treatment arm, cycle number and age predicted the scores of FM over the six cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Affect↗
PubMed1993

Phase II study of an oral combination of doxifluridine, prednimustine and idarubicin (FUPRIDA) for first line treatment of advanced breast cancer.

BACKGROUND: An oral combination chemotherapy for breast cancer may be of advantage for many patients, if its activity is equivalent to that of i.v. treatments. The bioavailability of oral idarubicin and of oral doxifluridine allows for their use in an oral 3 drug regimen. PATIENTS AND METHODS: Idarubicin 29 mg/m2 was given on day 1, doxifluridine 1500 mg and prednimustine 60 mg were given daily for 10-14 days (7 days/m2) in 17 patients with advanced breast cancer. Cycles (1 to 18) were repeated every 4 weeks or delayed if required by toxic effects. RESULTS: Nine responses were observed with durations ranging from 2 to 16 months. Responding lesions were the primary tumor, or skin, liver and bone metastases. WHO grade 3-4 toxic effects included leukopenia (7 patients), diarrhea and emesis (2 and 1 patient). There were no toxic deaths. CONCLUSIONS: If our results are confirmed, this oral 3-drug-combination is a safe and effective treatment that may improve the quality of lives of breast cancer patients with poor venous access.

Administration, Oral↗
PubMed1993

Early clinical trial of MDL 73.147 EF: a new 5-HT3-receptors antagonist for the prevention of chemotherapy-induced nausea and vomiting.

BACKGROUND: Like MDL 72.222, one of the first selective 5-hydroxytryptamine3 (5-HT3) receptors antagonist discovered, MDL 73.147 EF has been shown to possess antiemetic properties in the ferret model. We conducted a phase I study with MDL 73.147 EF in 31 patients, treated with emetogenic drugs over one to five days (cisplatin, cyclophosphamide, doxorubicin, dacarbazine). PATIENTS AND METHODS: 5 groups of at least 5 patients received rising unit doses of MDL 73.147 EF (10 to 50 mg) intravenously before chemotherapy, with two more doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting recorded by an independent observer. RESULTS: 51.6% of the patients were complete responders on day one and 40% on days two to five. One patient was given other rescue antiemetic therapy. Adverse events included constipation (25.8%), mildly elevated blood pressure (12.9%) and other minor events. No extrapyramidal effects have been reported. There was no suggestion of dose-dependent efficacy at the dose levels studied in this limited set of patients. CONCLUSIONS: We conclude that MDL 73.147 EF is a well tolerated and possibly effective antiemetic.

Adolescent↗
PubMed1993

Etoposide and secondary haematological malignancies: coincidence or causality?

BACKGROUND: Secondary haematological malignancies (SHM) induced by alkylating agents show cytogenetic abnormalities involving mainly chromosomes 5 and 7. Etoposide and other topoisomerase II inhibitors including anthracyclines induce secondary leukaemias with a short latency period, briefly preceded by a myelodysplastic phase, and frequently associated with balanced translocation characteristically involving the long arms of chromosomes 11 and 21. PATIENTS AND METHODS: Etoposide with doxorubicin containing chemotherapy was administered to 26 patients with Hodgkin's disease (HD), eight of whom received alkylating agents at relapse or progression, and to 59 patients with small-cell lung carcinoma (SCLC), thirty-three of whom received alkylating agents in the same combination. RESULTS: Four of 85 patients developed SHM of the myelodysplastic or acute myeloid type at, respectively, 20, 30, 35 and 38 months after therapy. In 3 of them, chromosome abnormalities were observed: two balanced translocations, t(6;9)(p23;34) and t(11;19)(q23;p13), and one monosomy 7q due to t(1;7)(cen;cen) with trisomy 8. The cumulative risk estimate of SHM is 12% (95% confidence interval (CI): 3%-46%) at 5 years for patients with HD and 18% (95% CI: 5%-49%) at 3 years for patients with SCLC. CONCLUSIONS: Our observations lend further support to the existence of SHM induced by topoisomerase II inhibitors that present early after initial treatment with balanced translocations to 11q23 and 21q22. However, other defects such as unbalanced abnormalities of chromosomes 5 and 7 can occur and may be related to the combination of topoisomerase II inhibitors with alkylating agents. Balanced t(6;9) was observed for the first time in SHM. A synergism between epipodophyllotoxins, anthracyclines, alkylating agents, cisplatin and radiotherapy is suggested, given the observed high risk of SHM.

Adult↗
PubMed1992

ABEP as primary chemotherapy for Hodgkin's disease.

20 untreated Hodgkin's disease patients and 1 patient relapsing after radiotherapy (17 stage IIB-IV and 4 stage I-IIA) were given doxorubicin, bleomycin, etoposide and prednisone on a 21-day cycle. The response rate was 95% and 16 patients (76%) achieved complete remission. 4 patients have relapsed 2, 5, 22 and 50 months after treatment. Survival was 100% at a median follow-up of 35 months. However, due to dyspnoea on exertion in 2 patients, bleomycin will be abandoned, and the occurrence of two second malignancies questions the role of etoposide as a leukaemogenic agent.

Aclarubicin↗