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Biomedical subjects

P Alberto

Publications and source records attributed to P Alberto.

At least 73 records · Page 4Linked to original sources

Phase I study of cyclohexylamine and lysine salt of mafosfamide.

Mafosfamide is a new oxazaphosphorine that breaks down spontaneously into 4-hydroxy-cyclophosphamide. A phase I trial with cyclohexylamine and lysine salts of mafosfamide was carried out in 16 patients, using weekly IV perfusion. Dose-limiting toxicities were not hematological, but consisted in the development of severe pain along the vein during administration. A particular mucosal syndrome with sneezing and conjunctivitis was seen only after administration of the lysine salt. The dose of 700 mg/m2 per week represents the maximum tolerated dose with this weekly schedule.

Adult↗

Etoposide, cisplatin and doxorubicin in patients with small cell lung cancer: tumor response and long term survival.

One hundred and fourteen patients with small cell lung cancer received a combination of etoposide 80 mg/m2 IV days 1,2,3,15,16,17, cisplatin 20 mg/m2 IV days 1,2,3 and doxorubicin 40 mg/m2 IV day 1, repeated every 4 weeks. The observation time from the initiation of treatment is longer than 4 years for all patients. An 85% response rate (38% complete response) was obtained after 1-4 cycles in 105 evaluable patients (96 without prior antitumour treatments). The response rate was not influenced by initial performance status and minimally by disease extension, whereas the same prognostic factors correlated significantly with complete responses. For limited disease and WHO performance 0 all responses were complete. For extensive disease and performance 3 no complete response was obtained. Various chemotherapy regimens with or without radiotherapy were used during the maintenance phase. Forty five per cent of first relapses were in the lung or mediastinum and 18% in the nervous system (20% without and 7% with prophylactic cranial irradiation). The median survival was 13.4 months for limited and 8.5 months for extensive disease, and correlated with performance and response. Only 2 patients survived free of disease after 4.8 and 5.5 years. We conclude that the induction treatment as used here produces a high rate of partial and complete responses but a low rate of long survivors.

Antineoplastic Combined Chemotherapy Protocols↗

Preliminary analysis of combined treatment with prednimustine and 4'epidoxorubicin in advanced breast cancer.

In an effort to define a well-tolerated therapeutic regimen for advanced breast cancer, we have studied a combination of 4'epidoxorubicin, 50 mg/m2 IV on day 1, and prednimustine, 100 mg/m2 PO on days 3 to 7 given every 3 weeks. Twenty-nine patients have been entered, and 22 are presently evaluable for response. Median age of the evaluable patients is 62 (range, 36 to 77), and median performance status (SAKK) is 2. Five patients had received chemotherapy, 16 hormonal therapy, five radiation therapy, and five no prior therapy for advanced disease. Most patients were in a high-risk group, with dominant visceral metastatic sites in 19 out of 22 cases. We have observed eight partial responses, nine no changes, and five progressions. Median response duration is 6 months. It is too early to discuss median overall survival. Toxicity is evaluable in 27 patients who received at least one course with a full dose of chemotherapy. Hematologic toxicity has been low, with only four patients having leukocyte nadirs below 2000/mm3 and three patients with thrombocyte nadirs below 100,000/mm3. Major alopecia (requiring a wig) was observed in eight patients. Emesis (controlled by minor antiemetics) was reported in six cases. This well-tolerated regimen is active in advanced high-risk elderly breast cancer patients, but dosage might be too low for younger patients and nonpretreated patients.

Adult↗

A clinical trial of aminoglutethimide in advanced postmenopausal breast carcinoma: low response in patients previously treated with medroxyprogesterone.

In an attempt to define the influence of prior hormonal treatments upon aminoglutethimide activity in advanced cancer of the breast, 42 heavily pretreated postmenopausal patients received aminoglutethimide, 4 X 250 mg daily, with hydrocortisone or cortisone. Twenty-six received high doses of medroxyprogesterone before entering this study. There was no significant difference in patients' characteristics with or without medroxyprogesterone pretreatment. A comparison of patients with and without prior medroxyprogesterone shows a significant difference in the response rate to aminoglutethimide-hydrocortisone (4 vs 32%, P = 0.02). In patients pretreated with tamoxifen but not with medroxyprogesterone the response rate to aminoglutethimide was 36%. These results suggest that aminoglutethimide has a low activity in breast cancer patients previously exposed to medroxyprogesterone, an agent with glucocorticoid-like activity inducing adrenal suppression.

Adult↗

Phase-II study of vindesine and hexamethylmelamine in patients with relapsing small cell carcinoma of the lung.

Twenty-five patients with measurable small cell lung cancer relapsing after first-line chemotherapy were treated with vindesine 3 mg/m2 IV on days 1 and 8 and hexamethylmelamine 100 mg/m2 PO on days 1-14, repeated every 3 weeks. Among 18 fully evaluable patients there was 1 partial remission lasting for 111 days. Two patients had disease stabilization for 127 and 152 days, respectively. Fifteen patients had disease progression. The treatment was well tolerated, myelosuppression being the major side-effect.

Adult↗

Phase II trial of mitomycin-C in patients with small cell carcinoma of the lung after failure on combination chemotherapy.

Mitomycin-C was evaluated in a disease-oriented phase II trial in patients with small cell lung cancer who had failed prior conventional chemotherapy. The drug was given as a direct i.v. injection of 15 mg/m2 repeated every 6 weeks. No objective tumor response was observed among 15 evaluable patients. This precludes a 20% level of activity with 95% confidence. Leukopenia (60% of patients) and thrombocytopenia (20% of patients) were common-effects observed. One patient developed a microangiopathic hemolytic anemia after a total mitomycin-C dose of 42 mg. We conclude that mitomycin-C in this dose and schedule is an inactive agent in previously treated patients with small cell lung cancer.

Adult↗

Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer.

In a randomized trial, 210 postmenopausal women with advanced measurable breast cancer were allocated to two different schedules of medroxyprogesterone acetate (MPA). In the induction phase they received either 1,000 mg intramuscular (IM) MPA (high dose) daily or 500 mg IM MPA (low dose) twice weekly for four weeks. The maintenance treatment consisted of 500 mg MPA IM once weekly for all patients. In total, 184 patients were considered evaluable. The response rate was significantly higher (p = 0.004) for patients receiving high-dose MPA (30 [33%] of 91) as compared to the women receiving the low-dose regimen (14 [15%] of 93) and was consistent across all prognostic subgroups. These prognostic subgroups included soft-tissue and osseous metastases, two metastatic sites, patients greater than 60 years, disease-free interval greater than 60 months, no prior chemotherapy, patients with a response to the last hormonal treatment before MPA, unknown estrogen receptors, and positive progestin receptors. The two different schedules of MPA did not influence the time to progression and the survival. Toxicity was similar in both regimens. These results confirm that a higher response rate can be achieved with a more intensive MPA schedule. This treatment may represent an ideal second-line choice in the endocrine therapy of advanced breast cancer; however, its role as a first-line treatment remains to be defined.

Age Factors↗

Combination chemotherapy for non-small cell lung cancer with doxorubicin and mitomycin or cisplatin and etoposide.

The combinations of doxorubicin (40 mg/m2 iv every 3 weeks) and mitomycin (12 mg/m2 iv every 6 weeks) or cisplatin (80 mg/m2 iv every 3 weeks X 3, then every 6 weeks) and etoposide (80 mg/m2 iv on Days 1-3 every 3 weeks X 3, then every 6 weeks) were evaluated in a randomized phase II trial in 77 patients with measurable or evaluable non-small cell lung cancer. No patient had been pretreated with prior chemotherapy. The overall response rate for the doxorubicin and mitomycin regimen was 11% and for the cisplatin and etoposide regimen was 23%. Responses lasted a median of 5.5 months. Median survival was 7.0 months for the doxorubicin and mitomycin regimen and 8.0 months for the cisplatin and etoposide regimen. One treatment-related death was observed after doxorubicin and mitomycin in a patient who had received radiation therapy immediately prior to study entry. Otherwise, the hematologic toxicity of both chemotherapy regimens was moderate, with only six patients (10%) having World Health Organization grade 3 toxicity and no patients having World Health Organization grade 4 toxicity. However, subjective tolerance gastrointestinal upset) of the cisplatin and etoposide combination was poor.

Adenocarcinoma↗

Concurrent or sequential use of cytotoxic chemotherapy and hormone treatment in advanced breast cancer: report of the Swiss Group for Clinical Cancer Research.

In a trial of combined hormone treatment and cytotoxic chemotherapy 464 patients with advanced breast cancer were randomly allocated to either concurrent or sequential treatment. Cytotoxic drugs were given only if the antitumour activity of the hormone treatment was inadequate. Hormone treatment consisted of oophorectomy for premenopausal and tamoxifen administration for postmenopausal patients. Length of survival was better, though not significantly, in premenopausal patients (p = 0.29) treated concurrently and in postmenopausal women (p = 0.17) treated sequentially; the difference was highly significant (p = 0.003) only for postmenopausal women in the low-risk category. The findings suggest that postmenopausal women with metastatic breast cancer should probably be treated primarily by carefully monitored hormone treatment.

Antineoplastic Agents↗

Randomized trial of 3 different regimens of combination chemotherapy in patients receiving simultaneously a hormonal treatment for advanced breast cancer.

We report the results of a randomized trial carried out by the Swiss Group for Clinical Cancer Research (SAKK) and in which 230 patients with advanced breast cancer receiving concurrently a hormonal treatment (oophorectomy for pre- and tamoxifen for postmenopausal women) were randomly allocated to three different regimens of combination chemotherapy. The therapeutic results registered with the two more intensive combinations (LMP/FVP and LMFP/ADM) were similar with regard to response rates, time to progression and survival. The patients receiving the low-dose chemotherapy lmfp showed a statistically significant lower response rate (32%, P less than 0.001) and a shorter survival (P = 0.03) than the results observed in patients treated with the two other regimens. This difference was particularly pronounced, at least regarding survival, in the following subgroups: postmenopausal women, patients with a poor performance status, dominant visceral lesions, two sites of disease and a disease-free interval longer than 12 months. Patients with bony metastases as dominant lesion fared similarly with all three regimens of chemotherapy. This latter subset of advanced breast cancer patients should probably be spared too intensive cytotoxic treatment. This is, to our knowledge, the first report of a randomized trial showing an evident correlation between response rate and survival in various subgroups of patients with advanced breast cancer treated with different chemotherapeutic regimens.

Antineoplastic Combined Chemotherapy Protocols↗

Phase II study of amsacrine in solid tumors: a report of the EORTC Early Clinical Trial-Group.

A total of 239 patients with advanced solid tumors were treated in this phase II trial. Amsacrine was administered as a single i.v. dose of 120 mg/m2 repeated at 21-day intervals. The initial dose was reduced to 90 mg/m2 in the case of extensive prior therapy. Some antitumor activity was detected in head and neck cancer but the drug appears to lack significant efficacy in epidermoid lung cancer as well as in carcinoma of the breast, melanoma, renal cell cancer, colorectal cancer and non-seminomatous testicular cancer. Leukopenia was the major toxic effect encountered in this trial and was similar at 90 and 120 mg/m2.

Adult↗

Phase II study of doxifluridine in advanced colorectal adenocarcinoma.

Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer. The drug was given in a five consecutive day schedule by a bolus intravenous injection at a dose of 4 g/m2 per day and repeated every three to four weeks. Of 42 eligible patients, 40 had no previous chemotherapy. Response was defined in 27 patients having received two or more courses of doxifluridine. Seven responses (26%) were observed. Responses were seen only in sigmoid and rectum primary tumors. Toxicity consisted mainly of leukopenia (53% of the evaluable patients), nausea and vomiting (38%). Other toxicities such as dermatitis, myocardial injury, and hair loss were also observed. Doxifluridine has therapeutic activity, albeit limited, in advanced rectosigmoid adenocarcinoma.

Adenocarcinoma↗

Role of chemotherapy in small cell lung cancer: a consensus report of the International Association for the Study of Lung Cancer workshop.

Many studies in small cell carcinoma of the lung (SCCL) have demonstrated a high response rate and a potential for cure in a subset of patients. Combination chemotherapy, the cornerstone of all treatment for SCCL, can produce up to 10% long-term, disease-free survival among all patients with SCCL and greater than or equal to 20% survival among patients who present with limited disease. Significant improvements in survival have occurred in all stages of disease, and further investigative efforts are necessary to improve the complete remission rate, the duration of response, and the percentage of long-term, disease-free survivors. The current report, based on the workshop on SCCL held in Ireland under the auspices of the International Association for the Study of Lung Cancer, reviews the current state of the art for chemotherapy and presents potential future directions.

Antineoplastic Agents↗

[Long-term survival after 1 or more recurrences of Hodgkin's lymphomas].

It is generally accepted that the prognosis in relapsing Hodgkin's disease is poor, and the literature contains few reports of cases that have involved one or more relapses and been cured. The evolution in 14 patients who suffered at least one relapse after initial complete remission is studied with respect to staging, histology, type of induction treatment, duration of complete remission, mode of relapse, type of retreatment and length of survival. Long term survival is reported despite one or more relapses, and it is concluded that relapsing Hodgkin's disease can be cured irrespective of the extension of the disease. The importance of an aggressive therapeutic approach in these cases is stressed.

Adolescent↗