Biomedical subjects
Publications and source records attributed to R Lionetto.
Twenty-nine patients with metastatic breast cancer were treated orally with idarubicin (15 mg/m2 X 3 days every 3-4 weeks). Objective response was seen in 31% of all patients. Toxicity was acceptable. There should be further clinical trials of new anthracycline antibiotic.
A phase II study with mitoxantrone has been carried out in 30 metastatic breast cancer patients. Of 26 evaluable patients 7 (26.9%) experienced a partial response; 7 (26.9%) patients had stable disease and 12 (46.1%) had progression. Major toxicity observed was: nausea and vomiting in 52% of patients, moderate hair loss in 53% of patients and leukopenia in 53%.
Aminoglutethimide, a drug known to block adrenal steroidogenesis and peripheral aromatization of androgens to estrogens, has been found effective in the treatment of breast cancer. The drug has been used in our Institute to treat 71 consecutive metastatic breast cancer patients. Of 67 patients evaluable for response, 9 (13.4%) have achieved a partial response, 30 (44.7%) stable disease, and 28 (41.7%) progression of disease. Four patients were taken off the therapy because of drug-related toxicity.
Mitomycin plus vindesine have been utilized as salvage therapy in metastatic breast cancer patients refractory to first line chemotherapy. No response was observed in 15 consecutively evaluable patients; according to the Gehan test a lack of effectiveness of this regimen is suggested at least in heavily pretreated patients.
BACKGROUND: In 183 patients with uncomplicated myocardial infarction, exercise-induced angina, ST segment depression, decrease in ejection fraction, or inadequate increase in systolic blood pressure and low exercise tolerance were significantly associated with 4-year incidence of hard ischemic events. METHODS AND RESULTS: Only the onset of both ST segment depression and a decrease in left ventricular ejection fraction with exercise was an independent predictor. ST segment depression and decrease in left ventricular ejection fraction had low sensitivity (61% and 70%) and specificity (56% and 51%) for hard ischemic events, but specificity increased to 78% when both were present. During medical therapy, 22 of 53 patients with both ST segment depression and a decrease in left ventricular ejection fraction with exercise had an ischemic event (i.e., 48.1% 4-year probability on Kaplan-Meier analysis vs 19.2% in the remaining 130 patients [p < 0.0005]). CONCLUSIONS: Even if no single variable, derived from exercise testing, is a highly sensitive and specific predictor, specificity increases to a clinically relevant level by combining ST segment depression and a decrease in left ventricular ejection fraction with exercise, and in this way patients with recent infarction may be selected for coronary arteriography.
BACKGROUND: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-alpha2a), for patients with metastatic melanoma. METHODS: Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6-18 x 10(6) IU/m2/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-alpha2a was administered subcutaneously at 3 X 10(6) IU three times each week until progression. RESULTS: Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 x 10(9) (range, 1-43 x 10(9)), and the median period of culture was 52 days (range, 45-60). rIL-2 was administered at doses ranging between 6 and 18 x 10(6) IU/m2/day. Toxicity was mild or moderate, and no life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2-35%). CONCLUSIONS: Outpatient treatment with TIL plus rIL-2 and rIFN-alpha2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone.
In this phase II study, we treated 7 patients, all males, with stage III or IV pancreatic cancer with goserelin (an LH-RH analogue). Goserelin was administered at a dose of 3.6 mg every 4 weeks. The tumour response was assessed by measuring lesions with US- or CT-scan studies, according to WHO criteria. No response was observed. The median survival was 8 months in locally unresectable tumours and 4 months in advanced disease. The accrual was actually stopped at 7 cases because there were no responses in either of our series or in those published during our study. The authors conclude that the treatment with LH-RH analogue alone cannot be recommended for further studies.
The Italian Group on Rare Tumors undertook a phase II study of a combination of epirubicin and interleukin-2 in 21 chemotherapy-naive patients with malignant mesothelioma. All patients had bidimensionally measurable disease at CT scan. Treatment included Intravenous administration of epirubicin at a dose of 110 mg/m2 i.v. on day 1, and interleukin-2 at a dose of 9 MU subcutaneously from day 8 to day 12 and from day 15 to day 19. Cycles were repeated every three weeks, up to six times in the absence of progressive disease. Treatment response was evaluated after two cycles of therapy. Only one patient achieved a partial response, resulting in an overall response rate of 5% (1/21) with a median progression-free and overall survival of 5 and 10 months, respectively. Toxicity was relevant and caused treatment discontinuation in many patients. These results do not support the use of such a combination in the management of malignant mesothelioma.
PURPOSE: To evaluate the maximum tolerated doses (MTD) of ifosfamide when given as a continuous infusion and in combination with fixed doses of bolus 4'-epidoxorubicin in advanced previously untreated adult soft tissue sarcoma patients. METHODS: Treatment consisted of epidoxorubicin, 60 mg/m2 days one and two, and ifosfamide, 1.5 g/m2 every 12 hrs as a 72-hr infusion, at the first level. Further levels of ifosfamide were defined as increments of 12 hrs of the same infusion program. G-CSF 300 microg/die was administered from days +7 to +14. Dose-limiting toxicity (DLT) was defined as: G4 leukopenia or thrombocytopenia of > or =5 days; any G3 neuro or nephrotoxicity; G4 toxicity of any kind. Patients had to complete at least 2 consecutive cycles, and MTD was defined as the level in which 20% of patients developed a DLT; 10-15 patients were entered in each level. RESULTS: First level: overall, 13 patients entered, 3 were not assessable for MTD, and only one developed a DLT. Second level: 18 patients entered, 3 were not assessable for MTD. Hematologic DLT was observed in 3/15 assessable patients. Therefore, the MTD was found at the ifosfamide level of 10.5 g/m2 given in 84 hrs. Eight patients of 29 assessable for response achieved an objective response: 1 complete and 7 partial. The overall response rate was 28% (95% CI: 13-47%). CONCLUSIONS: If we accept 4-day G4 leukopenia as a reliable cutoff for safety, ifosfamide intensification cannot be substantially exploited over already available schedules with the combination of ifosfamide and anthracyclines.
BACKGROUND: Chemotherapy with oxaliplatin, fluorouracil (5-FU) and leucovorin (LV) has proven efficacy in patients with advanced colorectal carcinoma (CRC), although the optimal dosage and administration schedule are still unclear. This phase II trial investigated the tolerability and activity of weekly oxaliplatin, high-dose infusional 5-FU and LV in pretreated patients with metastatic CRC. MATERIALS AND METHODS: Patients received weekly courses of i.v. oxaliplatin 50 mg/m2 (1-h infusion), LV 100 mg/m2 (1-h infusion) and 5-FU 2100 mg/m2 (24-h infusion) until disease progression or unacceptable toxicity. NCI-CTC criteria were used for assessment of side-effects (at each cycle) and WHO criteria for assessment of tumour response (every 8 cycles). For descriptive purposes, time to progression, overall survival and duration of objective response were also calculated. RESULTS: Forty-four patients were enrolled and received a total of 606 cycles (median 13/patient, range 4-33), and 70% of courses (421/606) were delivered at 100% of the planned dose. The most frequent side-effects were gastrointestinal and neurological and incidence rates were: diarrhoea 66% (grade III: 29%), nausea/vomiting 54%, neurotoxicity 34% (grade III: 2%), fatigue 27%, mucositis 22%, leucopenia 14%. No grade IV toxicity was observed. Objective response rates were: partial response 23% (10 patients), stable disease 59% (26) and progressive disease 11% (5). Median time to progression was 7 months, overall survival 13 months and the duration of partial response and stable disease were 9 and 6 months, respectively. CONCLUSION: The study demonstrated that this regimen has a favourable tolerability profile and is an active combination in the pretreated metastatic CRC patient, deserving further evaluation in phase III trials.
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Fourteen patients with advanced pretreated breast cancer were treated with vindesine in continuous venous infusion (1.5 mg/sm/24 hours for 72 hours every 3 weeks). A totally implanted venous access and a portable pump were used. A total of 33 courses was administered. No objective response was observed and treatment was stopped. Drug-related toxicity consisted mainly of alopecia (64% of patients), nausea and vomiting (29%) and mucositis (29%). Catheter - related toxicity was observed in 6 patients (43%) and consisted of infection of the skin pocket in 4 patients and dislodging of the needle and catheter break in one patient. The feasibility of continuous venous infusion of vesicant drugs in outpatients is discussed.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
BACKGROUND: Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken. PATIENTS AND METHODS: Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines. RESULTS: The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively. CONCLUSIONS: L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.