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A Brugarolas

Publications and source records attributed to A Brugarolas.

17 recordsLinked to original sources

Urokinase combination chemotherapy in small cell lung cancer. A phase II study.

BACKGROUND AND METHODS: Fifty-one patients with small cell lung cancer (SCLC) were treated with alternating urokinase (UK)-cyclophosphamide-doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-vincristine and cisplatin-etoposide-vincristine. UK was given as a loading dose of 3000 micrograms/kg body weight, followed by 3000 micrograms/kg/h for 6 hours. Thoracic irradiation with split technique (46 Gy) and prophylactic cranial irradiation (25 Gy) were administered to responding patients. A second staging was performed in patients exhibiting a clinical complete response (CR) after 1 year. RESULTS: In 27 patients with limited disease, there were 23 CR and 8 partial responses (PR) (CR, 85.1%; 66.2-95.8% at 95% confidence intervals); in 24 patients with extensive disease, there were 17 CR, 4 PR, and 3 cases with progression. Pathologically proven CR were observed in 59.2% patients with limited disease and 33.3% patients with extensive disease. Survival rates were as follows: in patients with limited disease, 1 year, 85.1%; 2 years, 55.5%; and 3 years, 25.9%; in patients with extensive disease, 1 year, 54.1; and 2 years, 16.9%. Median survival times were 26.3 months (patients with limited disease) and 13.3 months (patients with extensive disease). UK-related toxic effects included four episodes of mild to moderate bleeding, one allergic reaction, and one cerebrovascular accident. Myelotoxicity was severe, with a median of two episodes of Grade III-IV (World Health Organization classification) aplasia per patient. CONCLUSIONS: These results are consistent with a potential benefit of fibrinolytic therapy in combination with chemotherapy in patients with SCLC with limited disease. Additional trials are indicated.

Actuarial Analysis

[Infiltrating carcinoma of the bladder: preliminary results of multidisciplinary protocols with radiotherapy and neoadjuvant chemotherapy].

Report on the evolution of a series of 64 patients with T2-4 N0-3 M0 infiltrant transitional carcinoma of the bladder, treated with TUR and radical cystectomy (28/62) or intra-operative radiotherapy (IOR) 15 Gy and external radiotherapy 40 Gy prior to cystectomy (34/62). The last group including 24 patients which received neo-adjuvant chemotherapy. Seventy percent (15 p0N-, 5 p0N+, 1 p1N-, 3 p1N+) patients treated with radiotherapy, with and without chemotherapy, had local response. Considering just the group which received IOR, external radiotherapy and co-adjuvant chemotherapy (24/34), the local response accounts for 79% (10 p0N-, 5 p0N+, 1 p1N-, 3 p1N+). Current survival of the group receiving concomitant multiple therapy is 92 +/- 5%, 75 +/- 9% and 57 +/- 11% at 1, 3 and 5 years; for equal intervals current survival of the group undergoing cystectomy is 57 +/- 9%, 46 +/- 9% and 40 +/- 10% (p = 0.02). The univariate analysis has confirmed that stage decrease is significantly more frequent in the group receiving radiotherapy with and without chemotherapy (p less than 0.001). Such a decrease significantly biased survival (p = 0.001). In the multivariate analysis, the variables with greater prognostic power were pre-surgical renal function (p less than 0.001), use of radiotherapy (p less than 0.001) and surgical complications (p less than 0.001). Preliminary results show a very high local response to multiple therapy which has been translated so far in increased survival.

Actuarial Analysis

Iron toxicity studies of quelamycin.

A previous phase I study demonstrated excessive generalized toxicity (20 of 21 patients) and cardiotoxicity (eight of 21 patients) of single-day intermittent quelamycin (NSC-267703) treatment, and a modified schedule was recommended to overcome this acute toxicity. In the present study, 40 mg/m2 of quelamycin was administered iv on 2 or 3 consecutive days. This 2- or 3-day course was associated with a decrease in the incidence of general symptoms (five of nine patients) and a decrease in cardiotoxicity (none of nine patients). In addition, patients receiving multiple courses of quelamycin were evaluated. Clinical and pathologic findings supported the diagnosis of early hemochromatosis. In conclusion, quelaymcin administration was associated with acute and chronic iron-overloading toxicity. Acute iron toxicity was prevented by the administration of quelamycin at a dose of 40 mg/m2 iv on 3 consecutive days. On the other hand, hemochromatosis was an unexpected finding which requires further investigations before this drug is acceptable for broader studies.

Adolescent

Phase I clinical study of quelamycin.

A phase I clinical study was done with quelamycin, a recently synthesized triferric derivative of adriamycin. Twenty-one good-risk patients were studied: 19 patients with non-small cell carcinoma of the lung and two patients with metastatic sarcoma. Acute toxicity occurred in all patients and consisted of high fever, flushing, hypertension, generalized body aches, tremors, and confusion, which lasted 3-6 hours. Potentially dangerous cardiotoxicity occurred in eight patients who had previous minor rhythm disturbances, and was characterized by tachycardia, atrial extrasystoles, atrial fibrillation, and branch block which lasted 6-14 hours. The dose-limiting hematologic toxicity was found to occur at 125 mg/m2 iv single-dose. Objective responses were observed in three of 19 patients with lung cancer and in one patient with metastatic osteogenic sarcoma resistant to adriamycin therapy. In conclusion, quelamycin is a new derivative of adriamycin with potential interest. However, the acute generalized toxicity and the immediate cardiotoxicity found in the presently used schedule are excessive. Further studies directed to suppress these side effects are in progress.

Adolescent

Phase I and II clinical study of anhydro-ara-5-fluorocytosine (AAFC) and ICRF-159 combination in adenocarcinoma of digestive origin.

The results of a phase I--II study of a combination chemotherapy with AAFC and ICRF-159 in advanced adenocarcinoma of digestive origin are presented. Myelosuppression was the dose-limiting toxicity with anemia, leukopenia, and thrombocytopenia. The maximum tolerated dose of AAFC in the combination program was 650 mg/m2 I.V. weekly. ICRF-159 was given in a 3-day course every 3 weeks and the dose was escalated from 125 mg/m2 to 500 mg/m2 daily. Bone marrow toxicity was noticied at the first escalation level and all dose levels were similarly toxic. The results of this combination chemotherapy were: two partial responses in 14 patients with gastric cancer; no responses in nine patients with colorectal cancer; no responses in three patients with pancreatic cancer; and no responses in two patients with biliary tree cancer. In conclusion, AAFC and ICRF-159 combination chemotherapy demonstrated a low level of activity in advanced carcinoma of digestive origin. The peculiar hematologic toxicity found at the low-level dose requires further documentation and could make this drug association suitable for a phase II study in leukemia and/or lymphoma.

Adenocarcinoma

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