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Biomedical subjects

P Ruffie

Publications and source records attributed to P Ruffie.

At least 37 records · Page 2Linked to original sources
PubMed1992

Pleural mesothelioma.

Diffuse pleural malignant mesothelioma (DMM) is an uncommon tumor in the general population, but its incidence can be very high in persons exposed to asbestos. There has been controversy about the role of the different fiber types and their responsibility for causing DMM, particularly with chrysotile. Distinguishing between DMM and peripheral adenocarcinoma with pleural involvement is a frequent diagnostic problem. Immunohistochemical markers (positive for vimentin and negative for carcinoembryonic antigen and Leu M1) and electronmicroscopy aid in the diagnosis. Therapeutic results remain poor, and cure of DMM is rare. Local treatments such as surgery or radiation therapy are technically difficult because of the extent of disease. DMM continues to be a chemoresistant tumor. Because DMM is rare, study of this tumor has been hampered by the limited number of available patients in any given institution. Therefore, animal models or representative human malignant mesothelioma cell lines are needed for a dual investigation: first of the basic biology of this disease and second for a preclinical evaluation of chemotherapeutic agents and recombinant anticancer cytokines alone or in combination. Ongoing trials confirm that DMM is resistant to standard forms of therapy, but mesothelial cells are susceptible to immune effector cells and cytokines in in vitro and in vivo models. Thus, recombinant interferon-alpha, -beta, and -gamma have been used for both local and systemic treatment, as has interleukin-2 with and without autologous lymphokine-activated killer cells. In addition, substantial experimental evidence suggests synergy between cytotoxic drugs and cytokines.

Animals↗
PubMed1992

[Combination of chemotherapy (vindesine, lomustine, cisplatin, cyclophosphamide) and thoracic radiotherapy in nonresectable non-small cell bronchial carcinoma: final results of a phase II clinical trial].

Seventy-five patients with locally advanced non small cell lung carcinoma were entered in a phase II study combining chemotherapy (vindesine, lomustine, cisplatin and cyclophosphamide) and radical thoracic radiotherapy delivering a total dose of 60-65 Gy. Patients were regularly assessed by radiological and fiberoptic bronchoscopy examinations in order to evaluate local control. An objective response was observed in 22 patients (29%) after initial chemotherapy (2 complete remissions and 20 partial responses). The complete response rate after the combined schedule was 30%. Toxicity of this combination was acceptable. Median survival was 13.5 months. Actuarial risk of developing distant metastases at 3 years was 60%. However, the main cause of failure was local with 80% of uncontrolled or recurrent thoracic tumor in the first 2 years of follow-up. The present study shows that local control remains a major problem in the management of patients with inoperable non metastatic non small cell lung cancer.

Adult↗
PubMed1991

A phase II study of the combination of carboplatin and ifosfamide in previously untreated metastatic small cell lung carcinoma.

This Phase II study evaluated the combination of two active agents in small cell lung carcinoma (SCLC): carboplatin and ifosfamide. Thirty previously untreated patients (27 men and 3 women) with a median age of 59 years were included in this study. Twelve patients had one metastatic site and 18 had two or more metastatic sites. The median performance status was 80%. The chemotherapy (CT) regimen administered during the course of this study consisted of carboplatin (300 mg/m2) and ifosfamide (4 g/m2) plus mesna every 4 weeks. All 30 patients were evaluable: 1 achieved a complete remission (CR) and 18 achieved a partial remission (PR) (objective response rate, 63%). The median response time was 3 months and the median survival time was 8 months (range, 1 to 25+ months). Bone marrow toxicity was Grade III in three patients and Grade IV in four patients. The carboplatin and ifosfamide combination was well tolerated. No cross-resistance with the doxorubicin and etoposide regimen was established because 4 of 11 patients responded to this combination (+/- cisplatin) after failing to respond to the ifosfamide and carboplatin regimen. The ifosfamide and carboplatin combination may be considered for inclusion in non-cross-resistant alternating CT schedules.

Adult↗
PubMed1991

Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients.

We report the results observed in a large, randomized study that compared the effects of radiotherapy alone (the standard therapy) with those of a combination of radiotherapy and chemotherapy in nonresectable squamous cell and large-cell lung carcinoma. The radiation dose was 65 Gy in each group, and chemotherapy included vindesine, cyclophosphamide, cisplatin, and lomustine. In this study, 177 patients received radiotherapy alone (group A), and 176 patients received the combined treatment (group B). The 2-year survival rate was 14% in group A and 21% in group B (P = .08). The distant metastasis rate was significantly lower in group B (P less than .001). Local control was poor in both groups (17% and 15%, respectively) and remained the major problem.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Prognostic factors in patients with liver metastases from colorectal carcinoma treated with discontinuous intra-arterial hepatic chemotherapy.

48 patients with colorectal cancer metastatic to the liver were implanted with a subcutaneous access system allowing hepatic intra-arterial perfusion. Regional chemotherapy used 5-fluorouracil, while 17 patients also received low-dose mitomycin at the beginning of the study. Responses to the treatment occurred in 29 patients (60%) and median survival was 14.4 months. Toxicity included gastroduodenal erosions in 12.5% of the patients, leucopenia in 20.8%, catheter thrombosis in 42% and arterial thrombosis in 50%. 2 patients died of digestive haemorrhage probably related to treatment. When individually analysed, four factors were found to significantly affect survival: presence of hepatomegaly (defined as palpable liver edge exceeding the right costal margin by more than 5 cm) (P = 0.006), percentage of hepatic replacement superior to 50% (P = 0.003), more than four metastases (P = 0.025) and hypovascularised metastases at radionuclide liver scan with 99m technetium-labelled macroaggregate albumin (MAA) (P = 0.04). The effect of the four variables on the observed survival time was analysed using a Cox regression model. Two variables were found to have simultaneously influenced survival. Presence of hepatomegaly emerged as the more significant (P = 0.0001), the other being hypovascularised metastases at 99mTc-MAA.

Adenocarcinoma↗
PubMed1991

Influence of pretreatment clinical characteristics on the response rate to mitomycin/vindesine/cisplatin (MVP) in unresectable non-small cell lung cancer. ATTIT (Association pour le Traitement des Tumeurs Intra-Thoraciques).

The authors report their experience with the MVP (mitomycin/vindesine/cisplatin) regimen of the Memorial Sloan-Kettering Cancer Center (MSKCC) which showed the highest response rate in non-small cell lung cancer (NSCLC). The aim was to respect the original reported schedule to appreciate its activity, because the same drug combination with dose and schedule variations used by other investigators has failed to reproduce the original report results. 82 consecutive previously untreated patients with unresectable and/or metastatic NSCLC received mitomycin (8 mg/m2 days 1, 29, 71), vindesine (3 mg/m2, days 1, 8, 15, 22, 29, 43, 57, 71) and cisplatin (120 mg/m2, days 1, 29, 71), with evaluation on day 71. 24 objective responses were noted (29%) (2 complete response/22 partial response) (95% CI 19%-39%), without differences according to histology. Differences in median survival were noted according to the performance status and type of response. Overall survival rates in responding patients were similar to those noted with the original schedules. Analysis of selection criteria showed that there were more patients with bone (P less than 0.01) or liver metastases (P less than 0.05), less women (P less than 0.001) and less adenocarcinoma (P less than 0.001) than the MSKCC trial. A dose intensity analysis showed only a minimal difference in the average weekly doses of vindesine (10% lower than MSKCC trial: 1.8 mg/m2 vs. 2.25 mg/m2). Disease improvement, a subjective response criterion used in the MSKCC trial, was probably underestimated in the current study. We conclude that the potential benefit of chemotherapy with a three-drug combination in NSCLC is greatest in patients with stage IIIa and IIIb disease or stage IV disease with a good performance status and a low metastatic volume.

Adult↗
PubMed1991

ASTRO (American Society for Therapeutic Radiology and Oncology) plenary: Effect of chemotherapy on locally advanced non-small cell lung carcinoma: a randomized study of 353 patients. GETCB (Groupe d'Etude et Traitement des Cancers Bronchiques), FNCLCC (Féderation Nationale des Centres de Lutte contre le Cancer) and the CEBI trialists.

Most patients with locally advanced non small cell lung carcinoma are treated with external thoracic radiotherapy. Because of the high incidence of distant metastasis the addition of chemotherapy has been proposed. The present randomized study was conducted from June 1983 to February 1989 and included 353 patients. The trial compared arm A, thoracic megavoltage radiotherapy alone at a total dose of 65 Gy in 26 fractions and 45 days, to arm B that comprised the same radiotherapy preceded and followed by 3 monthly cycles of VCPC (vindesine 1.5 mg/m2 d 1-2, cyclophosphamide 200 mg/m2 d 2-4, cisplatinum 100 mg/m2 d 2 and lomustine 75 mg/m2 d 3). Disease was deemed unresectable but non-metastatic after bronchoscopic, radiologic, CAT, and nuclear scans and physical examinations. Only patients in clinical, radiological, endoscopic, and histological complete remission were considered as locally controlled; these patients were monitored by fiberoptic bronchoscopy and systematic biopsies to the primary site. One hundred seventy-seven patients received thoracic radiotherapy alone and 176 received the combined modality. Twenty-seven percent of arm B patients had an objective response after 2 VCPC cycles. At the time of final assessment, performed 3 months after the end of thoracic radiotherapy in both arms, there were 20% of complete responders in arm A versus 16% in arm B. The two-year survival rate was 14% in arm A versus 21% in arm B (p = 0.08, logrank test). The distant metastasis rate was 67% in arm A versus 45% in arm B (p less than 0.001). Local control at 1 year was poor in both groups (17% and 15%, respectively). The striking effect of VCPC chemotherapy on the incidence of distant metastasis did not have a significant impact on overall survival. We conclude that thoracic tumor control remains a significant problem in unresectable non small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Alternating radiotherapy and chemotherapy in 173 consecutive patients with limited small cell lung carcinoma. GROP and the French Cancer Center's Lung Group.

One-hundred seventy-three patients with limited small cell lung cancer were included in three consecutive protocols alternating radiotherapy and chemotherapy. The alternating schedule consisted of six courses of chemotherapy (doxorubicin, VP16213, cyclophosphamide, and methotrexate in the first protocol; methotrexate being replaced by cisplatinum in the other two protocols) and three series of thoracic radiotherapy delivering a total dose of 45, 55, and 65 Gy in each consecutive protocol. Radiotherapy was started after the second course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy percent of patients were in complete remission at the end of the induction treatment. The actuarial 5-year local control was 60% and the 5-year overall survival was 18%. Sixty percent of patients developed distant metastases. The death rate unrelated to cancer was 10%. These results show that alternating radiotherapy and chemotherapy schedules are reproducible, and provide a consistent long-term local control and a long-term survival rate exceeding 15% in limited disease.

Adult↗
PubMed1989

Limited small cell lung cancer treated by combined radiotherapy and chemotherapy: evaluation of a grading system of lung fibrosis.

A grading system of radiological fibrosis was defined and applied by four observers for the reading of 218 posterior-anterior chest X-rays of 78 patients. These patients with limited small cell lung cancer were treated from May 1980 to July 1983 in two consecutive alternating radiotherapy-chemotherapy schedules. Chest X-rays performed at each 6-month interval were read by each observer. A second reading was performed the day after. The analysis of results showed that in spite of some systematic variations in intra- and inter-observations, the proposed grading system had a good reproducibility. The radiological lung fibrosis score progressed between 6 and 12 months but was stable after one year of follow-up. There was no difference in the score of lung fibrosis between the two protocols which delivered a total dose of 45 and 55 Gy to the mediastinum. There was no significant correlation between the radiological changes and clinical symptoms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.

Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.

Adult↗
PubMed1989

Limited small cell lung cancer: possible prognostic impact of initial chemotherapy doses.

While the effect of chemotherapy dose on tumor response in small cell lung cancer has been fairly well established, the effect on survival has been retrospectively analyzed only in some series. This particular point was studied in a series of 52 consecutive patients with limited small cell lung cancer treated by an alternating radiotherapy-chemotherapy schedule. The induction treatment consisted of 6 chemotherapy cycles (the planned doses were: doxorubicin 40 mg/m2 day 1, VP16213 75 mg/m2 days 1-3, cyclophosphamide 300 mg/m2 days 3-6, and cisplatinum 100 mg/m2 day 2) alternated after the first 2 cycles with 3 courses of thoracic radiotherapy delivering a total dose of 55 Gy. Eighty-one percent of patients went into complete remission and the 3-year relapse-free survival was 24%. A multivariate analysis of prognostic factors took into account age, sex, T stage, performance status, delayed hematological toxicity to the first course of chemotherapy, actual dose/m2 of each drug during the first course and mean dose/course delivered during the induction treatment after the first cycle of chemotherapy. It was possible to identify 3 independent factors influencing overall survival and relapse-free survival: actual initial dose of cisplatinum, actual initial dose of cyclophosphamide and the T stage. The effect of the initial dose of cisplatinum and cyclophosphamide proved to be linear on relapse-free survival. The results of this analysis show a possible effect of initial doses of chemotherapy in the management of limited small cell lung cancer in terms of both distant metastasis and overall survival rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Relationship between tuberculous scar and carcinomas of the lung.

Results of a transversal case-control study are reported which shows that there is a statistically significant association between tuberculous scars and carcinoma of the lung. Accordingly the possibility of malignancy has to be kept in mind when radiological or scintigraphic scanning reveal the presence of lung scars.

Cicatrix↗
PubMed1985

[Alternating chemotherapy and radiotherapy in the induction treatment of small cell bronchial carcinoma (forms limited to the thorax)].

Sixty three patients with limited small cell lung carcinoma were entered into a pilot study alternating monthly cycles of combination chemotherapy (doxorubicin, VP16213, cyclophosphamide and methotrexate (group A) or cis platinum (group B) with 3 courses of mediastinal radiotherapy. The total mediastinal dose was 45 Gy for the first 28 patients (group A) and 55 Gy for the remaining 35 (group B). The complete response rate was 86% in group A (median survival 14 months) and 91% in group B (median survival 20 months). Local control at two years was 61% in group A and 82% in group B, while relapse-free 2 year survival rates were 32% and 37% respectively. The acceptable toxicity and high response rate of this combined modality therapy lead us to further research in maintenance therapy.

Antineoplastic Agents↗