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V Bonfante

Publications and source records attributed to V Bonfante.

46 records · Page 3Linked to original sources

Toxic and therapeutic activity of 4'-epi-doxorubicin.

A Phase I-II study with 4'-epi-doxorubicin (epi-DX) was performed in 108 patients with various types of advanced malignancy. The pattern of acute toxicity was similar to that of doxorubicin (DX). However, epi-DX was better tolerated than DX because of comparative lower incidence of vomiting, stomatitis, complete alopecia and severe myelosuppression. Cardiac toxicity was studied by utilizing noninvasive methods, and the electrocardiographic results suggested a slightly lower cardiac damage after epi-DX compared to DX. Antitumor activity was documented in a variety of neoplasms, and objective response was also observed in those considered refractory to DX such as malignant melanoma and renal cancer. X

Adolescent↗

Alternating drug combinations in the treatment of advanced Hodgkin's disease.

Of 75 consecutive patients with Stage IV Hodgkin's disease, we assigned 38 to receive MOPP alone (mechlorethamine, vincristine, procarbazine, and prednisone) and 37 to receive MOPP alternating monthly with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) - a combination of drugs not cross-resistant with MOPP. Complete remission was documented in 71 percent of the patients receiving MOPP alone and in 92 per cent of those receiving the alternating regimen (P = 0.02). At five years, there was no progression of disease in 37 per cent of the MOPP group and in 70 per cent of the MOPP-plus-ABVD group (P less than 0.0001). After chemotherapy, the median relapse-free survival period was 20 months in the MOPP group and over 31 months in the MOPP-plus-ABVD group (P less than 0.01). Five-year survival with no evidence of disease was 84 per cent in patients given MOPP and ABVD and 54 per cent in those given MOPP alone (P less than 0.005). We conclude than alternating non-cross-resistant combinations appear promising in the management of advanced Hodgkin's disease and are worthy of trial in other malignant diseases.

Adult↗

Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin's disease.

Fifty-five consecutive patients with advanced recurrent Hodgkin's disease resistant to MOPP chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone) were given ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine). In 54 patients evaluable for response, complete remission after pathologic restaging was seen in 59% and partial remission in 13%. Fifteen of 29 patients (52%) showing disease progression during primary MOPP treatment achieved complete remission after ABVD. The median time to complete response was 3 months. The median duration for complete remission was 17 months, and 38% of patients who attained complete remission have remained alive and continuously disease free at 5 years from start of ABVD treatment. The median survival of complete responders was more than 60 months. Toxic manifestations were moderate, aside from pronounced vomiting in more than half of patients. These results indicate that ABVD is an effective salvage regimen for MOPP-resistant Hodgkin's disease.

Adolescent↗

Cyclic delivery of MOPP and ABVD combinations in Stage IV Hodgkin's disease: rationale, background studies, and recent results.

This paper summarizes the experience achieved at the Cancer Institute of Milan with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy in various stages of Hodgkin's disease, with special emphasis on the cyclic delivery of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) and ABVD in the primary treatment of stage IV disease. Six cycles of ABVD yielded a complete remission (CR) rate (71%) similar to that of MOPP (63%). ABVD combined with radiotherapy in 153 patients with stage IIB, IIIA, or IIIB disease was superior to MOPP plus radiotherapy in the CR induction (94% vs 79%, P less than 0.01), particularly in the presence of nodular sclerosis histology (P less than 0.03) and B symptoms (P = 0.01), as well as in the relapse-free survival of patients with pathologic stage IIIA disease (ABVD, 100%; MOPP, 68%; P = 0.02). Total survival was similar between the two treatment groups, but, compared to MOPP, ABVD chemotherapy was associated with a lower incidence of delayed toxic effects such as azoospermia, prolonged amenorrhea, and cancerigenesis. ABVD induced CR in 59% of 54 patients resistant to MOPP; 37.5% of the complete responders remain alive and disease-free at 5 years. The cyclic delivery of MOPP and ABVD was significantly superior to that of MOPP alone in terms of CR (92% vs 71%; P = 0.02), freedom from disease progression (70% vs 37%; P less than 0.0001), and relapse-free survival (77% vs 47%; P less than 0.01) at 5 years. Toxic effects were similar between the two treatment groups, but there was a higher incidence of vomiting and alopecia following ABVD chemotherapy; in the group given MOPP alone, one patient who had previously failed extensive irradiation developed acute nonlymphocytic leukemia. ABVD is confirmed to be an effective regimen that is non-cross-resistant to MOPP and devoid of late morbidity. Therefore, its administration, when alternated monthly with MOPP, offers the possibility to improve the cure rate of Hodgkin's disease.

Adult↗

Preliminary clinical experience with 4-epidoxorubicin in advanced human neoplasia.

4'-Epidoxorubicin (epi-DXR) was tested in 56 patients with various types of advanced malignancies. The pattern of acute toxicity was similar to that of doxorubicin (DXR), but epi-DXR produced a lower incidence of vomiting, stomatitis, alopecia, and myelosuppression. The study of cardiac toxicity, utilizing only noninvasive methods, indicated that epi-DXR also is cardiotoxic. The increase in the systolic time intervals after the first dose as well as after cumulative doses was slightly lower compared with that observed after DXR. Antitumor activity occurred in a variety of tumors including malignant melanoma, renal cancer, and rectal cancer, which are refractory to DXR. Present results suggest that further studies with epi-DXR are indicated.

Adolescent↗

Preliminary phase I study of 4'-epi-adriamycin.

A phase I study of 4'-epi-Adriamycin (4'-epi-ADM) was performed in 22 patients with various types of advanced solid tumors. Very preliminary results would indicate that the drug produces a pattern of acute toxicity which is similar to that of Adriamycin. However, the incidence of vomiting, alopecia, and marrow suppression was less pronounced than that of Adriamycin. 4'-Epi-ADM prolonged the systolic time interval, although no patient presented clinical signs of cardiotoxicity. Two patients with renal carcinoma and malignant melanoma showed objective improvement. Present results suggest that further clinical studies with 4'-epi-ADM are indicated.

Adult↗

Anaplastic lymphoma kinase (ALK) is not expressed in Hodgkin's disease: results with ALK-11 antibody in 327 untreated patients.

The t(2;5)(p23;q35) or other rare chromosomal abnormalities involving 2p23 upregulate the ALK gene, which is not expressed in normal lymphocytes. Thus, detection of ALK protein is presumptive evidence of these 2p23 abnormalities. The t(2;5) and ALK immunoreactivity are common in anaplastic large cell lymphoma of T/null-cell lineage. However, a small subset of cases of Hodgkin's disease (HD) have been reported to either carry the t(2;5) or express ALK. In this study, we have immunohistochemically evaluated 327 cases of HD with the ALK-11 antibody. ALK-11 is a well characterized polyclonal antibody raised against an intracellular portion of the ALK protein. We detected ALK-11 immunoreactivity in 8 (2.4%) cases of HD. We further studied these positive cases with ALK-1 monoclonal antibody, which reacts with an intracellular portion of ALK, similar to ALK-11. All 8 ALK-11 positive cases were negative for ALK-1. These results indicate that rare cases of HD may react with ALK-11 antibody, similar to previous reports by others using different polyclonal anti-ALK antibodies. However, the absence of ALK-1 expression in these HD cases suggests that ALK protein is not truly present and that polyclonal anti-ALK antibodies may rarely yield non-specific cross reactivity. These results further support the use of anti-ALK antibodies in the differential diagnosis of HD from ALCL.

Adolescent↗

Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease.

PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38% of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.

Adolescent↗

Lung function and serum concentration of tumor necrosis factor-alpha, interleukin-6 and fibronectin in patients treated with ABVD chemotherapy followed by radiotherapy for mediastinal Hodgkin's disease.

UNLABELLED: Mediastinal radiotherapy and polychemotherapy regimens can produce late toxicity leading to pulmonary fibrosis. There is evidence for the involvement of various cytokines in this process. We evaluated lung function in 20 patients with stage I-IIA Hodgkin's disease and submitted to chemotherapy including bleomycin (ABVD) and radiotherapy. Lung function tests were performed before, at the end of treatment and after a median of 12 months from the end of therapy. Tumor necrosis factor-alpha (TNF-alpha), fibronectin and interleukin-6 (IL-6) were determined on serum samples collected at the same time intervals. A modification of tests indicative of a restrictive lung disease was observed at end of treatment, whereas a persistent decline of transfer lung factor for carbon monoxide (DLCO) was documented. TNF-alpha constantly decreased, fibronectin increased and IL-6 showed a decline after treatment and a rise during the follow-up but the differences were not statistically significant. No significant correlations were observed between changes of lung function tests and serum cytokine concentration. CONCLUSIONS: This lack of correlation could be due to: a) incorrect selection of serum collection time, or b) to the fact that cytokine plasma concentration does not reflect events occurring in the alveolar phase.

Adult↗

Late pulmonary toxicity after treatment for Hodgkin's disease.

The combination of mediastinal radiotherapy (RT) with chemotherapy (CT) including bleomycin is associated with an increased risk of pulmonary toxicity. The aim of the present investigation was to evaluate late pulmonary effects of RT plus CT consisting of the ABVD regimen in patients suffering from early stage Hodgkin's disease. For this purpose pulmonary function was serially evaluated before, at the end and at least 1 year after therapy in 32 patients (median age 28 years) with Hodgkin's disease stages IA,B-IIA. Treatment consisted of four cycles of ABVD chemotherapy followed by mediastinal irradiation at the median dose of 36 Gy (range 30.6-43.2). At the end of treatment, resting mean pulmonary function tests showed a significant decline of forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25-75%, (FEF25-75%), total lung capacity (TLC), vital capacity (VC) and carbon monoxide diffusing capacity (DLCO). The decline of TLC, VC and DLCO, indicative of a pulmonary defect of restrictive type, persisted 1 year from the end of therapy. Only seven patients developed symptoms of cough and mild shortness of breath with effort. These data confirm that RT combined with short term ABVD result in pulmonary dysfunction that does not seem to have clinical significance.

Adolescent↗