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R Arriagada

Publications and source records attributed to R Arriagada.

At least 91 records · Page 5Linked to original sources
PubMed1992

Post-mastectomy megavoltage radiotherapy: the Oslo and Stockholm trials.

The ability of adjuvant radiotherapy to prevent distant metastasis and to prolong survival in patients with early breast cancer is much debated. The paper presents a joint analysis of long-term results (13-16 years' follow-up) from the Oslo and Stockholm randomised trials of post-operative megavoltage radiotherapy versus surgery alone. Among node-positive patients there was a significant 37% relative reduction of distant metastases with radiation (P less than 0.01) and an overall survival difference in favor of the irradiated patients which corresponded with a 22% relative reduction of deaths of borderline significance (P less than 0.06). No significant benefit with radiation in terms of distant metastasis-free survival or overall survival was observed among node-negative patients. The results show that effective local treatment can prevent distant dissemination in some patients and contradict the contention that node-positive breast cancer invariably is a systemic disease already at primary diagnosis.

Adult↗
PubMed1992

Competing risks determining event-free survival in early breast cancer.

To evaluate the natural history of a disease and the effects of therapeutic interventions, it is important to determine which are the causes of treatment failure and to assess the extent to which each cause contributes to the total failure rate. The paper presents a new biostatistical technique to decompose the total event-free survival of a diseased population into cause-specific failure rates. The technique was based on a competing risk approach thereby avoiding biases related to assumptions of independence between different types of event. Such assumptions are inherent in the conventional Kaplan-Meier or actuarial methods. The competing risk method was used to analyse the pattern of failure among 2,850 pre- and postmenopausal patients with early-stage breast cancer and the results were compared to those obtained using conventional methods. The following events were analysed: loco-regional recurrence, distant metastasis, contralateral breast cancer, other new primary malignancies, and intercurrent deaths. The rate of new primary malignancies was found to be significantly higher in post- than in premenopausal patients (6% vs 3% at 10 years). In low-risk, node-negative postmenopausal patients the incidence of recurrences from breast cancer were found to be no greater than other types of events. This observation highlights the significance of the effect of different adjuvant therapies not only on the disease itself but also on the risk of second primary malignancies and other intercurrent diseases. In general, it was found that the conventional statistical methods tended to overestimate the event-specific rates. In conclusion, the method based on competing risks permits an unbiased analysis of all types of events determining the total event-free survival. It is thus useful for the description of the natural history of breast cancer as well as other diseases.

Aged↗
PubMed1992

Competing events determining relapse-free survival in limited small-cell lung carcinoma. The French Cancer Centers' Lung Group.

PURPOSE: We report results in terms of relapse-free survival (RFS), obtained in patients with limited small-cell lung carcinoma (SCLC) treated by four consecutive alternating protocols, using a competing risk approach with local recurrences, distant metastases, and death unrelated to cancer as competing events. PATIENTS AND METHODS: Two hundred two patients with limited SCLC were included in four consecutive protocols alternating radiotherapy and chemotherapy (CT). The alternating schedule consisted of six cycles of CT (doxorubicin, etoposide [VP16213], and cyclophosphamide [CAVP16], plus methotrexate in the first protocol; cisplatin replaced methotrexate in the other three protocols) and three courses of thoracic radiotherapy at a total dose of 45, 55, 65, and 61 Gy in the four consecutive protocols, respectively (accelerated hyperfractionation was used in the first course of the fourth protocol). A 1-week rest followed each CT cycle and each course of radiotherapy. Seventy-six percent of patients were in complete remission at the end of the induction treatment. RFS variables were determined according to a model assuming competing risks to define the first cause of failure (local disease, distant metastasis, or intercurrent death). RESULTS: No significant differences were observed between the four treatment groups. Overall results showed a 2-year cumulative incidence rate of failure of 75%. When analyzed, the first cause of failure was local recurrence only, 33%; distant only, 25%; distant and local simultaneously, 9%; and intercurrent death, 8%. CONCLUSIONS: The methodology of competing risks allowed an unequivocal description of first events in limited SCLC. The extent of the local problem has been relatively overshadowed by the use of conventional descriptive methods.

Antineoplastic Combined Chemotherapy Protocols↗
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

Adjuvant chemotherapy in early breast cancer and incidence of new primary malignancies.

Adjuvant chemotherapy is increasingly being given to patients with early breast cancer. Long-term follow-up studies suggest a higher frequency of secondary tumours, especially leukaemias, among women receiving such cytotoxic drugs. We studied the frequency of new primary malignancies in 1113 patients with early breast cancer who had been included in a randomised trial to compare chemotherapy as an adjunct to primary surgery with adjuvant locoregional radiotherapy. The estimated rate of new primary malignancies at ten years was significantly lower (p less than 0.0003) in the chemotherapy group (1%) than in the radiotherapy group (6%). The corresponding rate among 1986 patients treated with surgery alone was 5%. Our findings suggest that adjuvant chemotherapy in early breast cancer may protect against the development of new primary tumours in the first ten years of follow-up.

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

Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences.

An analysis of the chest recurrences was conducted in 72 consecutive patients with limited small cell lung cancer treated in two successive phase II trials alternating six induction chemotherapy courses and three series of thoracic radiotherapy, followed by maintenance chemotherapy. The total radiation dose was 45 Gy (3 series of 15 Gy) in the first trial, and 55 (20, 20 and 15 Gy) in the second. The effect of the irradiated volume was investigated by comparing the local relapse rates in the group of patients treated by radiation fields encompassing the initial tumor volume to another group in which the initial target volume was not fully covered by radiation fields. The definition of these two groups was performed retrospectively by examination of radiological, fiberoptic bronchoscopy initial findings, technical radiation charts and check films. The local recurrence rate were 33 and 36% in each group (no significant difference). This finding could suggest that tumor shrinkage after chemotherapy might allow the use of "reduced" radiation volumes. However, the limited number of patients does not permit a definite conclusion. The effect of radiation dose was investigated by comparing the local control rates in the two consecutive trials which delivered 45 and 55 Gy, respectively. No difference in long-term local control was found: the addition of 10 Gy in the second trial only seemed to delay the appearance of local recurrences by 6 months. Twenty percent of patients died from a local relapse without evidence of distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
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↗
PubMed1991

Liquid chromatography with amperometric detection of some sulphonamides and their N4-acetyl-metabolites in serum and urine.

Sulphonamides separated on a C18 LC column were detected at lower levels using amperometric detection at a glassy carbon electrode in comparison with UV detection at 258 nm. Whereas sulphonamides are detectable at a potential of +1.00 V, their N4-acetyl-metabolites required a potential of +1.25 V to be detected after their separation by LC. An interference commonly present in serum and urine, which co-eluted with one of the analytes, was detected at 1.25 V. This was overcome with an appropriate sample preparation in which 150 microliters of serum or 75 microliters of urine were first diluted to 1.5 ml with phosphate buffer (pH 3.0; 0.2 M). A 1.0 ml volume of this solution was then passed through an Extrelut 1 column. The analytes were eluted with dichloromethane, which was evaporated under vacuum, and redissolving the analytes in an appropriate volume of mobile phase, i.e. methanol-phosphate buffer (pH 6.7; 0.067 M) (25:75, v/v). For sulphamethoxazole (SMX) and sulfamethoxypyridazine (SMP) and their N4-acetyl-metabolites the calibration curves were linear between 1.5 x 10(-7) and 8 x 10(-6) M. The recovery ranged between 92.6 and 97.6% in serum and between 80.5 and 99.4% in urine. Detection limits were 10 times lower with amperometric detection than with UV detection. The method has been applied to the quantitation of SMX and SMP and their N4-acetyl-metabolites in serum and urine after their oral administration.

Acetylation↗
PubMed1990

Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes?

The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer.

Adenocarcinoma↗
PubMed1990

Pilot study of neoadjuvant ifosfamide, cisplatin, and etoposide in locally advanced non-small cell lung cancer.

33 patients with locally advanced non-small cell lung cancer entered a study of neoadjuvant chemotherapy to evaluate the response rate with ifosfamide/cisplatin/etoposide and the complete resection rate and safety of surgery following chemotherapy. Chemotherapy with cisplatin 25 mg/m2, ifosfamide 1.5 g/m2, and etoposide 100 mg/m2 was given on days 1-4 of a 21 day cycle and repeated for three cycles. For responders, surgery was done 15-20 days after haematological recovery. Chemotherapy induced 5 complete responses (15%) and 18 partial responses (55%). 77% of the 33 patients had grade 3-4 neutropenia and 60% grade 3-4 thrombocytopenia. 1 patient died with a central nervous system haemorrhage. Thoracotomy was done in 21 patients but resection was only possible in 20 (61%). A complete resection was achieved in 18 patients (55%). Histology was negative for the 5 complete responses. Surgery induced no morbidity. A high response rate may be obtained with ifosfamide, cisplatin and etoposide neoadjuvant chemotherapy allowing a high complete resection rate.

Adult↗
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↗
PubMed1990

Alternating radiotherapy and chemotherapy in non-metastatic inflammatory breast cancer.

Ninety-nine patients presenting with non-metastatic inflammatory breast cancer were treated with an alternating protocol of radiotherapy and chemotherapy. The alternating schedule consisted of 8 courses of combined chemotherapy, including doxorubicin, vincristine, cyclophosphamide, methotrexate and 5-Fluorouracil, and 3 series of loco-regional radiotherapy delivering a total dose of 65 to 75 Gy to the breast tumor, 65 Gy to the axilla, and 50 Gy to the supraclavicular and internal mammary chain lymph nodes. Radiotherapy was started after the third course of chemotherapy. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. Seventy-five percent of patients were in complete remission at the end of this induction treatment. The 3-year local control was 72% and the 3-year overall survival rate was 70%. An isolated local recurrence was observed in only 4% of patients. Approximately one-half of patients developed distant metastases. These results show that alternating radiotherapy and chemotherapy schedules deserve further investigation in locally advanced breast cancer.

Adult↗