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Biomedical subjects

F Cavalli

Publications and source records attributed to F Cavalli.

At least 199 records · Page 11Linked to original sources

Phase II trial of nimustine (ACNU; 3-[4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride) in patients with small cell carcinoma of the lung after failure on combination chemotherapy.

Thirty-nine previously treated patients received Nimustine in a phase II trial to test the therapeutic activity in refractory small cell lung cancer. Nimustine was given as a direct i.v. injection of 100 mg/m2 with treatments repeated every six weeks. Three partial remissions of 56, 123 and 355 days duration were noted among 34 evaluable patients. Thrombocytopenia was prominent with a median platelet nadir of 47,000/microliter. We conclude that Nimustine has minor antitumor-activity in heavily pretreated patients with small cell lung cancer. The definitive value of Nimustine in the treatment of small cell lung cancer, as well as its superiority over its parent compounds remains to be established.

Aged↗

Phase II study of 5'-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma.

Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily X 5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts less than 1.5 X 10(9)/l leukocytes or 50 X 10(9)/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.

Drug Evaluation↗

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↗

Combination of chemotherapy with methotrexate, bleomycin, and cis-platinum, and radiation therapy for locally advanced carcinoma of the cervix.

Sixteen non-pretreated patients with locally advanced cervical cancer (FIGO Stage IIIb) were treated with two 3-week cycles of platinum, bleomycin, and methotrexate (PBM), which were followed by radiation therapy. Response to both modalities was seen in 11 patients (69%), and three patients (19%) had a progression-free survival of more than 2 years. Radiation therapy was proven to be feasible after two cycles of PBM combination chemotherapy.

Adult↗

Efficacy and clinical cross-resistance of a new combination therapy (AMSA/VP16) in previously treated patients with acute nonlymphocytic leukemia.

We investigated the tolerance, efficacy, and clinical cross-resistance of a new combination chemotherapy in 38 patients with previously treated acute myeloblastic leukemia (AML). It consisted of 120 mg2/d 4'(9-acridinylamino) methanesulfon-m-Anisidide (m-AMSA) in a one-hour infusion and 80 mg/m2/d etoposide (VP-16) in a 24-hour infusion, both administered for 5 days. The first 27 patients also received vinblastine, 6 mg/m2 on day 8, but this therapy was discontinued because of intestinal complications. Thirteen of 23 patients (56%) at first or subsequent relapse and five of 15 patients (33%) who were primarily resistant to an anthracycline/cytarabine combination achieved a complete response (CR) (hemoglobin level not taken into account) with a median CR duration of 5 months and 2 months, respectively. The response rate was as high as 63% for patients at first or second relapse whether the remission was maintained or not. The median times to recovery of normal bone marrow cellularity, of blood granulocyte counts greater than 500/microL, and of platelets greater than 20,000/microL were 34, 27, and 22 days, respectively. Marked but reversible gastrointestinal toxicity was observed in 24% of the patients, and two patients died of infection during induction. The one-hour AMSA/continuous VP-16 combination is effective for patients with relapsing AML and shows no cross-resistance in a proportion of patients refractory to the standard anthracycline-cytarabine combination.

Adolescent↗

Pharmacokinetics of etoposide in patients with abnormal renal and hepatic function.

Etoposide (VP16) pharmacokinetics was investigated in three groups of cancer patients: a control group of 18 patients with renal and hepatic function tests in the normal range; a group of 8 patients with renal insufficiency; and a group of 15 patients with abnormal hepatic function. In the control group plasma clearance (Clp), volume of distribution (Vd), and elimination half-life (t1/2 beta) of VP16 were, respectively, 22.8 +/- 1.0 (SE) ml/min/m2, 11.4 +/- 0.8 liters/m2, and 5.6 +/- 0.4 h. In patients with renal insufficiency Clp was 12.8 +/- 1.1 ml/min/m2, Vd was 20.8 +/- 4.9 liters/m2, and t1/2 beta was 19.2 +/- 4.7 h. A statistically significant correlation (P = 0.0000001) was found between VP16 Clp and creatinine clearance. In 12 of 15 patients with abnormal liver tests Clp, Vd, and t1/2 beta were, respectively, 27.9 +/- 2.7 ml/min/m2, 12.4 +/- 1.5 liters/m2, and 5.4 +/- 0.6 h and are thus similar to those of the control group. In the other three cases with abnormal liver function VP16 plasma levels were very low. In these cases VP16 t1/2 beta values were similar (5.1, 4.4, and 5.1 h) whereas Clp values (320, 87, and 96 ml/min/m2) and Vd values (142, 33, and 42 liters/m2) were much larger than in controls. These results suggest that VP16 doses should be reduced in patients with renal function impairment but not necessarily in patients with liver impairment. The high VP16 Vd and Clp values found in a subset of patients with liver impairment require further elucidation.

Adult↗

[Clinical characteristics of immature T-type (negative E-rosette) acute lymphoblastic leukemia detected by LAU-A1 monoclonal antibody].

Immature T-ALL is a newly defined subgroup of ALL in which the blasts lack the receptor for sheep erythrocytes (ER) and the usual T-cell markers, but express the 40 kDa pan-T surface antigen recognized by our monoclonal antibody LAU-A1. Patients with immature T-ALL represent 10% of all cases of adult ALL. Leukocyte counts are lower and spleen, liver and lymph node enlargement is less prominent, but mediastinal enlargement is more frequent than in mature (ER-positive) T-ALL. 7 patients with immature T-ALL (median age 42 years, range 13-73) were treated with intensified chemotherapy regimens, and only one 47-year-old female entered a short-lived complete remission. The overall survival of our patients was poor (median 7.5 months, with only one patient surviving at 15 months) and seemed not to be influenced by age. Our study indicates that immature T-ALL can only be accurately identified by the use of monoclonal antibodies recognizing the 40 kDa pan-T antigen, and that immature T-ALL is a separate disease entity typified by a poor prognosis.

Adolescent↗

Phase-I trial of 4-demethoxydaunorubicin in acute leukaemias.

Eleven patients with heavily pretreated acute leukaemia were treated with 4-demethoxydaunorubicin. Dosages were escalated from 7 mg/m2/d to 15 mg/m2/d for 3 consecutive days. One patient achieved a partial remission and antitumor activity was seen in most other patients. Stomatitis was dose-limiting at 15 mg/m2. Phase II trials are warranted and we propose a schedule of 12 mg/m2/d for 3 consecutive days.

Acute Disease↗

Epirubicin in colorectal cancer. A phase II study of the early clinical trials group (EORTC).

Epirubicin, a stereoisomer of doxorubicin with suggested lower potential for cardiotoxicity in experimental animal tumor systems, was studied in a disease-oriented phase II trial in patients with advanced colorectal cancer. The drug was given as a direct iv injection of 90 mg/m2 q 3 weeks. No objective response was observed in 52 evaluable patients with colon (n = 34) and rectal (n = 18) carcinoma. Fourteen patients (27%) had stable disease for a median of four treatment courses. Leukopenia (88%), nausea and vomiting (71%) and alopecia (54%) were the most common toxic effects. We conclude that epirubicin at the present dose and schedule is an ineffective agent in patients with metastatic colorectal cancer.

Adult↗

Progestin therapy for breast cancer: a panel discussion.

The use of pharmacologic doses of steroid hormones to treat patients with advanced breast cancer has been standard for many years. Recently there has been increased interest in the investigation of progestational agents, largely as a result of their excellent response rate in selected patients and their minimal side effects. In this panel discussion the participants discuss the use of progestin in advanced and early breast cancer. Criteria for patient selection, such as receptor status or response to previous therapies, are analyzed, and dose-response relationship and the side effects are addressed.

Breast Neoplasms↗

Hormono-chemotherapy in the treatment of advanced breast cancer.

The current situation in the treatment of metastatic breast cancer is reviewed. Overall the concurrent use of endocrine treatment and chemotherapy does not improve the therapeutic results as compared to a treatment encompassing only one modality. However, results diverge widely in different subgroups. Data emerging from various randomized trials are beginning to define subgroups of patients, who should be treated differently. Such data are discussed and their importance for future trials in the field of advanced breast cancer reviewed.

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 I trial of 1,2,4-triglycidylurazol (TGU, NSC 332488): a new triepoxide cytostatic agent.

1,2,4-Triglycidylurazol, a new triepoxide derivative, was chosen for phase I trial because of its favorable water solubility, stability and antitumor activity in murine systems. Fifty-seven patients were evaluable. Hematologic toxicity was dose-limiting, with a steep dose-toxicity curve. At 650 mg/m2 2/10 patients developed grade II toxicity. Seventeen patients were treated at 800 mg/m2 and seven developed grade III or IV toxicity according to WHO. Five of these patients had received greater than 3 cytotoxic agents and/or extensive radiotherapy. One toxic death was seen. Cumulative toxicity was observed with respect to hematologic values in a comparison of the first and second courses. Sixteen patients developed phlebitis after injection, not dose-dependent and not dose-limiting. Response was noted in three patients, two non-small cell lung cancers and one bladder cancer. Recommended doses for phase II trials are 800 mg/m2 q 4 weeks for patients who have received less than or equal to 3 cytotoxic agents and 650 mg/m2 q 4 weeks for heavily pretreated patients.

Adult↗