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Biomedical subjects

P Alberto

Publications and source records attributed to P Alberto.

At least 91 records · Page 5Linked to original sources

[Simultaneous or sequential hormono/chemotherapy and a comparison of various polychemotherapies in the treatment of metastatic breast cancer].

Since in the treatment of advanced breast cancer chemotherapy and the various hormonal manipulations seem recently to have reached a plateau of effectiveness when used alone, it is widely assumed that the combination of both treatment modalities could improve therapeutic results. The outcome is reported of a study encompassing 109 pre- and 297 postmenopausal evaluable cases with previously untreated metastatic breast cancer. The patients were randomized either to a concurrent chemo/hormonotherapy or to the hormonal treatment alone, chemotherapy being delayed until the occurrence of tumor progression. All patients were further randomized to 3 chemotherapy regimens (LMFP, LMP/FVP, LMFP/ADM) representing three different degrees of intensity. Pre-menopausal patients tend to live longer with the concurrent combination of both modalities, whereas postmenopausal patients fare better when chemotherapy is delayed until the occurrence of tumor progression with hormonotherapy alone. However, the differences in survival are statistically significant only in postmenopausal patients with a less aggressive tumor ("low-risk"). The more aggressive cytotoxic combinations elicit higher response rates than "minimal chemotherapy", but the differences translate only marginally into different survivals. These findings are discussed with regard in particular to their importance in establishing widely acceptable therapeutic rules for the treatment of advanced breast cancer.

Adult↗

Phase I clinical study with 5'-deoxy-5-fluorouridine, a new fluoropyrimidine derivative.

5'-Deoxy-5-fluorouridine (DFUR) is a new fluoropyrimidine derivative with significant antineoplastic activity in animal systems. Compared to 5-FU or other fluoropyrimidines, DFUR has a more favorable therapeutic ratio in Sarcoma 180-bearing mice. DFUR was studied in this phase I trial with a daily x 5 bolus iv injection. A second course was given greater than or equal to 3 weeks after the first day of treatment. Doses were escalated from 300 to 5000 mg/m2/day in 30 patients. Dose-limiting factors were myelosuppression and stomatitis. Hematologic toxic effects were particularly marked on granulocytes. Thrombocytopenia was less frequently encountered. Stomatitis was severe at high doses of DFUR. Eleven patients had nausea or moderate vomiting. Drug-induced myocardial injury may exist, since electrocardiogram changes were recorded in two patients. After rapid iv injection, four patients felt hot in the face and pelvis. Other side effects were minimal. With this daily x 5 schedule of administration, the maximum tolerated dose of DFUR appeared to be 5000 mg/m2/day. The dose recommended for further clinical use is 4000 mg/m2/day x 5 for patients previously untreated with chemotherapy.

Adult↗

[Long-term tumor-free surviving patients with anaplastic small cell bronchial cancer].

Report on 12 patients with small cell lung cancer who achieved disease-free survival for over 24 months after initial therapy. All the cases were classified as limited disease. Median age was 62 years and median performance status 0. Only 2 patients had weight loss of more than 5% in the six months prior to the diagnosis. Four patients were treated by local therapy alone (surgery in 3, radiotherapy in 1). Eight patients received systemic treatment (chemotherapy in 4, chemotherapy plus radiotherapy in 4). Median duration of cytostatic treatment was 17 months, with 3 of 8 patients receiving chemotherapy for less than 6 months. Three patients relapsed 27, 34 and 54 months after initial treatment. Median survival is 52 + months. It is concluded that long term disease-free survival can be achieved in patients with limited disease small cell lung cancer, even where initial treatment is relatively short.

Adult↗

[The toxicity/efficacy relationship in polychemotherapy of lung neoplasms].

Although it is generally accepted that anti-cancer chemotherapy should be administered at the maximum tolerable dose, it is not clearly established that the therapeutic results at dosage levels involving maximum tolerable toxicity are really superior to those with lower, better tolerated doses. 392 patients with advanced primary lung cancer were treated with 5 chemotherapy regimens including cyclophosphamide, methotrexate, vincristine, procarbazine, hydroxyurea, adriamycin and CCNU, in combinations of 3 to 7 agents. Response rates of 50% and over were registered after 8 weeks of treatment. During the same time the intensity of leukopenia, thrombocytopenia, vomiting, other digestive toxicity, neurologic disorders and alopecia was graded according to the worst observation from 0 to 4. The results show that there is no correlation between the grade of toxicity and the rate of response either for the whole group or for subgroups of patients as defined by cell type, degree of dissemination, age, or performance status. They demonstrate that the search for maximum tolerable toxicity is not a sine qua non for the best possible response to chemotherapy in primary lung cancer.

Adenocarcinoma↗

5-Fluorouracil: a comparative pharmacokinetic study and preliminary results of a clinical phase I study.

Until now it was unknown, whether 5-fluorouracil (5-FU) would be absorbed sufficiently after oral application, so that therapeutical effects could be expected. For this reason a comparative pharmacokinetic study of intravenous versus oral application was performed on six patients, as well as a pilot study on 13 patients with adenocarcinomas of different origins. The results show that 5-FU is absorbed rapidly. The biological availability increases with higher dose, which would indicate a saturation of the "first pass" in the liver. The clinical study shows partial remission in seven patients, with hepatoma and tolerable signs of bone marrow depression, decrease of hemoglobin, leukocytes and platelets after oral application of 5-FU in doses of 1,000-1,250 mg on days 1, 3, 5, 8, 10, and 12. 5-FU can therefore be given successfully at an adequate dose by the oral route.

Administration, Oral↗

Combined chemotherapy of head and neck squamous cell carcinomas with methotrexate, bleomycin, and hydroxyurea.

Thirty-two patients with squamous cell carcinoma of head and neck not amenable to surgery or radiotherapy were treated with a combination of methotrexate 0.6 mg/kg IV weekly, bleomycin 15 mg IV weekly, and hydroxyurea 1,000 mg/m2 three oral doses weekly. Eleven complete responses and ten partial responses of more than 50% were observed. The mean duration was 43 weeks for complete responses and 35 weeks for partial responses. Toxicity consisted in leukopenia, thrombocytopenia, nausea, vomiting, stomatitis, and cutaneous alterations. Only one patient suffered reversible lung toxicity. These results suggest that a combination of three drugs in squamous cell head and neck cancer may be more effective than a combination of bleomycin and methotrexate only.

Antineoplastic Agents↗

Tumor localization of radio-labeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation.

Purified, [131I]-labeled goat antibodies against carcinoembryonic antigen, which have been shown to localize in human carcinoma in nude mice, were injected into 27 patients with carcinoma. Patients were scanned with a scintillation camera at various intervals. In 11 patients, radioactivity was detectable in the tumor 48 hours after injection. Computerized subtraction of blood-pool radioactivity provided clearer pictures in positive cases, but in 16 patients the scans remained doubtful or negative. To study the specificity of [131I]-antibody localization, we gave some patients simultaneous injections of [125I]-labeled normal IgG. Both isotopes were measured by means of scintillation counting in tumors and normal tissues recovered after surgery. The results demonstrated that only the anti-CEA antibodies localized in tumors. However, the total antibody-derived radioactivity in the tumor was only about 0.001 of the injected dose. We conclude that, despite the present demonstration of specificity, this method of tumor detection is not yet clinically useful.

Aged↗

Simultaneous hormone- and chemotherapy, compared with hormone therapy followed by chemotherapy in the treatment of metastasising mammary carcinoma--preliminary results of a current study.

The preliminary results of an on-going SAKK study on metastasising mammary cancinoma are reported. At the time of writing 210 cases are already evaluable. This study seeks to investigate the question of the necessary intensity of polychemotherapy and also the problem of whether cytostatic therapy should be begun at the same time as hormonal therapy or just after failure of this measure. At present no definite answer is available. The results point to a new, possibly important aspect of the treatment of metastasising mammary carcinoma.

Antineoplastic Agents↗

Use of limitations of radiolabeled anti-CEA antibodies and their fragments for photoscanning detection of human colorectal carcinomas.

Fifty-three patients with histologically proven carcinoma were injected with highly purified [131I]-labeled goat antibodies or fragments of antibodies against carcinoembryonic antigen (CEA). Each patient was tested by external photoscanning 4, 24, 36 and 48 h after injection. In 22 patients (16 of 38 injected with intact antibodies, 5 of 13 with F(ab')2 fragments and 1 of 2 with Fab' fragments), an increased concentration of 131I radioactivity corresponding to the previously known tumor location was detected by photoscanning 36-48 h after injection. Blood pool and secreted radioactivity was determined in all patients by injecting 15 min before scanning, [99mTc]-labeled normal serum albumin and free 99mTc04-. The computerized subtraction of 99mTc from 131I radioactivity enhanced the definition of tumor localization in the 22 positive patients. However, in spite of the computerized subtraction, interpretation of the scans remained doubtful for 12 patients and was entirely negative for 19 additional patients. In order to provide a more objective evaluation for the specificity of the tumor localization of antibodies, 14 patients scheduled for tumor resection were injected simultaneously with [131I]-labeled antibodies or fragments and with [125I]-labeled normal goat IgG or fragments. After surgery, the radioactivity of the two isotopes present either in tumor or adjacent normal tissues was measured in a dual channel scintillation counter. The results showed that the antibodies or their fragments were 2-4 times more concentrated in the tumor than in the normal tissues. In addition, it was shown that the injected antibodies formed immune complexes with circulating CEA and that the amount of immune complexes detectable in serum was roughly proportional to the level of circulating CEA.

Animals↗

[Prognostic factors of survival and tumor recurrence following surgery and radiotherapy for breast cancer with positive axillary nodes. La Chaux-de-Fonds, 1968-1975].

Survival and treatment failure are analyzed in a homogeneous group of 70 pre- or post-menopausal patients with operable breast cancer and histologically involved axillary nodes. From March 1968 to December 1975, all patients underwent simple or radical mastectomy, followed by radiotherapy in 67. The period of observation varied from 11 months to 10 years. Treatment failures were observed on 34 patients: 10 loco-regional relapses, 21 distant metastatizations, and 3 tumors in the other breast. Analysis of actuarial survival curves shows a statistically significant difference between patients with 1 to 3 positive axillary nodes and patients with 4 or more, but no difference with regard to the volume of the tumor and the patient's age. Comparison of disease-free period curves shows statistically significant differences between patients aged below and over 55 years, tumor of less or more than 2 cm, and 4 or fewer axillary nodes. These results are comparable to those in the literature and form a contribution to a Swiss study of post-operative adjuvant chemotherapy in breast cancer with positive axillary nodes.

Adult↗