Search PubMed⌕ Search

Biomedical subjects

G Bonadonna

Publications and source records attributed to G Bonadonna.

At least 217 records · Page 12Linked to original sources
PubMed1986

Salvage chemotherapy in Hodgkin's disease irradiation failures: superiority of doxorubicin-containing regimens over MOPP.

One hundred and twenty-two consecutive patients with Hodgkin's disease who relapsed after primary curative irradiation were treated with either MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) or a doxorubicin-containing regimen (ADM-Reg). The main pretreatment characteristics were comparable in the two groups. Complete remission was achieved in 74.6% of patients treated with MOPP (44 of 59) and in 90.5% of those given ADM-Reg (57 of 63). No difference was observed in the incidence of complete remission with regard to the type of ADM-Reg utilized [MABOP (mechlorethamine, doxorubicin, bleomycin, vincristine, and prednisone), 92.9%; ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), 95.6%; and MOPP alternated with ABVD, 84.6%]. The superiority of ADM-Reg versus MOPP was also confirmed in the 7-year analysis of freedom from disease progression (73.2% vs 42.2%), relapse-free survival (81.2% vs 54.3%), and overall survival (80.5% vs 44.4%). Thrombocytopenia was less frequently observed with ADM-Reg (30%), particularly following ABVD (13%), compared to MOPP (73%). The lowest incidence of alopecia occurred in patients given MOPP (15%) or MOPP/ABVD (19%). Acute nonlymphoblastic leukemia was observed in patients treated with MOPP (five of 59) and MABOP (one of 14). The observed findings indicate that in patients failing to respond to primary radiotherapy, salvage regimens containing doxorubicin are more effective than MOPP. Furthermore, combinations devoid of procarbazine and alkylating agents (ABVD) or with less intensive administration of these drugs (MOPP/ABVD) were not associated with secondary leukemia.

Adolescent↗
PubMed1986

[Prognostic factors in breast carcinoma].

The prognostic factors in breast cancer are numerous and interdependent. The single most important variable is the total tumor cell burden as well as the marked heterogeneity of tumor cell population. In women with clinical localized disease, the progressive increase in the diameter of primary tumor is associated with higher incidence of histologically involved axillary nodes; in turn, this involvement, and particolarly its extent, represents an indirect sign of distant micrometastases. In women with clinical advanced disease, the extent of tumor cell burden (inflammatory carcinoma, multivisceral involvement) is associated with a decrease in the response rate by drug therapy. The percent of drug-resistant neoplastic cells is inversely related to the tumor mass; this resistant fraction represents today the limiting factor to a more effective contribution of medical treatment (i.e. long-term complete remission and cure) in all stages of breast cancer. The concept of breast cancer as systemic disease in a higher percent of women than thought in the past, allows to perform breast-saving procedures without affecting prognosis and stimulates treatment strategies utilizing a combined modality approach for high-risk women.

Axilla↗
PubMed1986

Phase II study of doxorubicin versus epirubicin in advanced breast cancer.

Doxorubicin and its epimerized analog epirubicin were tested at a dose of 75 mg/m2 given iv every 3 weeks to 42 patients with advanced breast cancer, 23 of whom were in relapse from prior cyclophosphamide, methotrexate, and 5-FU (CMF) chemotherapy. The median cumulative dose was 540 mg/m2 (range, 225-650) for doxorubicin and 565 mg/m2 (range, 150-600) for epirubicin. Complete plus partial response was documented in 11 of 21 patients (52%) following doxorubicin and in 13 of 21 patients (62%) following epirubicin. The median observation period was 22 months (range, 14-30); the median duration of response and the median survival were superimposable. Doxorubicin and epirubicin exhibited a superior response rate in previously untreated patients [six of eight (75%) vs eight of 11 (73%)] compared to those previously given CMF with or without endocrine therapy [five of 13 (38%) vs five of ten (50%)]. Vomiting, mucositis, and leukopenia were documented less frequently following administration of epirubicin as compared to doxorubicin. Regarding cardiac evaluation, no significant differences were evident between the two drugs. However, a significant fall in the left ventricular ejection fraction was documented in women who received doxorubicin following a cumulative dose greater than 550 mg/m2. Following completion of doxorubicin therapy at cumulative doses of 580 and 562 mg/m2, two women developed left ventricular failure at 6 and 14 months, respectively. Epirubicin appears to be an effective drug for the treatment of breast cancer and, given at equal doses, is less toxic than doxorubicin.

Adult↗
PubMed1986

Current status of Milan adjuvant chemotherapy trials for node-positive and node-negative breast cancer.

This report summarizes the most important clinical results achieved at the Milan Cancer Institute through various randomized trials with systemic adjuvant chemotherapy. In the study testing surgery versus surgery plus 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in node-positive patients, the reduction in failure rate (34%) significantly favored CMF-treated patients (P less than 0.001). Despite a reduction in the death rate of 23%, the overall survival showed only a trend for CMF compared to surgery alone (P = 0.10). In a second study, the 8-year results confirmed the lack of difference in relapse-free survival and total survival rates between patients who received 12 and 6 cycles of CMF. The third study indicated that at 6 years, postmenopausal women who had 1-3 positive lymph nodes and were treated with full-dose sequential non-cross-resistant combinations had rates of relapse-free survival and total survival that were superior to those previously achieved with CMF in the same menopausal subset. In a limited series of patients with negative axillary nodes as well as negative estrogen receptors, there was clear evidence of very poor prognosis in women given only local-regional therapy, compared to women treated with adjuvant CMF. Within the node-negative subset, the proliferative activity (labeling index) of the primary tumor appears to be a more effective prognostic discriminant than estrogen receptor status. The proportion of primary drug-resistant tumor cells as well as the lack of relative dose intensity in the drug programs tested so far probably represent the two most important causes for the failure of adjuvant chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cytarabine and cisplatin in advanced malignant melanoma.

Twenty-seven consecutive patients with advanced malignant melanoma were treated with cytarabine (Ara-C) and cisplatin. Of 25 evaluable patients, four achieved partial response, for a median duration of 3 months. Three of four responders belonged to the group of seven patients given Ara-C at a dose of 3 g/m2. The predominant toxic effect was hematologic and related to the dose of Ara-C. The cost-benefit ratio of this combination is inferior to that of dacarbazine or carmustine alone.

Aged↗
PubMed1985

Spectrin extractability from erythrocytes in Duchenne muscular dystrophy patients and carriers and in other myopathies.

Spectrin extractability was measured in the erythrocyte membranes from patients with Duchenne Muscular Dystrophy (DMD), from DMD definite carriers (in whom serum creatine kinase (CK) was also measured) and patients affected by other myopathies. After the extraction of spectrin from ghosts with EDTA, membrane proteins were examined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Spectrin extractability was also investigated in the presence of an excess of calcium. Spectrin extraction from erythrocyte ghosts was significantly reduced with respect to controls in DMD patients, in DMD definite carriers and in patients affected by limb-girdle dystrophy, but not in patients suffering from other non-dystrophic myopathies. Fifty percent of DMD definite carriers showed a reduced extraction of spectrin and some of them had normal serum CK. Reduced extractability was also observed in red blood cells incubated in media containing excess calcium. Our results could suggest that reduced spectrin extractability is connected with a modification of intracellular calcium levels.

Adolescent↗
PubMed1985

Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer.

The paper reviews all adjuvant studies carried out since 1973 at the Milan Cancer Institute in women with resectable breast cancer and positive axillary nodes. The updated results essentially confirm previous findings, and indicate that CMF-based chemotherapy is able to exert a prolonged therapeutic activity in a fraction of patients bearing micrometastases. In particular, the first randomized study testing no postoperative chemotherapy vs 12 CMF cycles, showed a 10-year relapse free survival (RFS) of 31.4% vs 43.4% (P less than 0.001) and an overall survival (OS) of 47.3% vs 55.2% (P = 0.10), respectively. Findings related to subsets indicated that RFS and OS benefit was significant in premenopausal and not in postmenopausal women, and in both treatment groups the observed findings were always related to the number of histologically positive nodes. On relapse, salvage therapy administered to controls failed to produce superior results compared to those achieved in the CMF group. The 8-year results of the second study testing 12 vs 6 CMF cycles failed to show a significant difference between the two treatment groups. This indicated that the maximum tumor cell kill occurred during initial chemotherapy cycles. In the third study, carried out only in postmenopausal women less than or equal to 65 years, sequential non-cross resistant combinations (CMFP----AV) at full dose achieved superior results compared to CMF in the subset with limited nodal extent. Acute side effects were moderate and no delayed morbidity, including increased incidence of second neoplasms, was observed. We conclude that the tumor cell heterogeneity, and in particular primary drug resistance, represents the major obstacle to adjuvant systemic therapy in high risk breast cancer. Current results suggest that 6 cycles of CMF can be considered a simple, safe, and moderately effective adjuvant therapy. Future trials should contemplate treatments of different intensity related to major prognostic subsets, while in women at very high risk of early relapse more vigorous drug regimens should be concentrated within the first six months from local-regional therapy.

Adult↗
PubMed1985

Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD.

The comparative gonadal toxicity following two equally effective and non-cross-resistant regimens (MOPP and ABVD) was prospectively evaluated in 53 males with Hodgkin's disease. The median age was 29 yr (range 16-45). MOPP produced azoospermia in 28/29 patients (97%) while ABVD induced oligoazoospermia in 13/24 patients (54%). Follicle-stimulating hormone levels were consistently and significantly increased after MOPP while their median value remained within normal range after ABVD. Sperm count was repeated in 34 patients. Recovery of spermatogenesis occurred in 3/21 cases treated with MOPP and in all 13 cases given ABVD. Present findings confirm that the two alkylating agents, mechlorethamine and procarbazine, included in the MOPP regimen cause sterility in most patients while the drugs included in ABVD are not associated with permanent gonadal dysfunction.

Adolescent↗
PubMed1985

Prospective randomized trial in advanced malignant melanoma with cis-platinum, vindesine, and etoposide vs. cis-platinum, vindesine, and lomustine.

Thirty-seven consecutive patients with disseminated malignant melanoma and previously untreated with chemotherapy were randomly allocated to receive vindesine, cis-platinum, and etoposide (Regimen A) or vindesine, cis-platinum, and lomustine (Regimen B). In 31 evaluable patients, Regimen A induced an overall response rate of 31% and a complete response rate of 6%; with Regimen B the corresponding findings were 20% and 20%, respectively. The median duration of complete response was 12 months with both regimens and the comparative median total survivals were 8 and 6 months, respectively. In no case was toxicity so severe to require treatment discontinuation, and the major dose-limiting side effect was myelosuppression, especially in the patients treated with Regimen B. Present results confirm once more the limited activity of drugs and regimens presently utilized in the treatment of advanced malignant melanoma.

Adult↗
PubMed1985

Carnitine kinetics during dialysis. Evidence of unilateral transport from tissues to plasma.

Plasma total and free carnitine concentrations were measured in 14 patients during a 4-hour hemodialysis session at 40-min intervals. Although postdialysis carnitine levels were lower than predialysis levels, they did not drop progressively and rebound occurred early or late. While no relationship was seen between pre- and postdialysis carnitine values, an inverse correlation was found when the predialysis value was compared with an end-dialysis to predialysis ratio. Our data are not consistent with a first-order elimination kinetics of the molecule and suggest that during dialysis carnitine may be actively released from tissue stores to plasma pool. The finding of an inverse correlation between the fractional change (post-pre ratio) of plasma carnitine and its predialysis level suggests that plasma carnitine supply from cells is more active when plasma carnitine levels are lower.

Adult↗
PubMed1985

Chemotherapy of malignant lymphomas.

Chemotherapy of malignant lymphomas has entered the exciting era in which cure can be expected in a large portion of untreated patients, even those with advanced-stage disease. The major obstacle to complete remission is selection and overgrowth of a permanent, drug-resistant, neoplastic cell population. For this reason, a number of investigators have tested the efficacy of two or more non-cross-resistant regimens delivered in alternating fashion. In stage IV Hodgkin's disease, the MOPP-ABVD program increases the cure rate by 15% to 20% compared with MOPP alone. With intensive polydrug regimens, at least 50% of patients with diffuse large-cell non-Hodgkin's lymphomas (NHL) can now be cured. The risk of treatment-induced acute leukemias as well as sterility can be avoided or greatly decreased with drug combinations not including procarbazine HCI and alkylating agents. Effective salvage regimens for lymphomas resistant to primary chemotherapy have been described in part for Hodgkin's disease; a number of second-line treatments can probably cure 20% to 25% of MOPP-resistant patients. Encouraging results that require confirmation have also been reported in the treatment of relapsing NHL with drug combinations including cisplatin (Platinol), cytosine arabinoside, etoposide (VP-16), ifosfamide, and amsacrine. Salvage drug therapy combined with autologous bone marrow transplantation appears promising but, at present, remains experimental.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Prognosis of bulky Hodgkin's disease treated with chemotherapy alone or combined with radiotherapy.

The medical records of 396 consecutive patients with a histological diagnosis of Hodgkin's disease were reviewed to assess the prognostic importance of bulky and non-bulky lymphomas. The presence of large lymphadenopathy failed to affect significantly the seven-year results in terms of complete remission (bulky 81.1% v. non-bulky 86.2%), freedom from progression (60.7% v. 65.6%), relapse-free survival (75.1% v. 76.5%) and overall survival (62.7% v. 68.9%). It is noteworthy that in all subsets, ABVD (Adriamycin + bleomycin + vinblastine + dacarbazine), either combined with irradiation or alternated with MOPP (mechlorethamine + vincristine + procarbazine + prednisone), yielded superior results compared with MOPP with or without irradiation. Given the prognostic importance of various bulky sites, the presence of large lymphadenopathy in anatomic regions other than the mediastinum failed to affect results adversely. On the contrary, in patients in stages IIB-IIIA-IIIB, treated with combined modality, the presence of bulky mediastinal involvement did influence prognosis compared with patients with positive but non-bulky mediastinum. At seven years the results were 60.2% v. 79.9% for freedom from progression, 73.2% v. 89.9% for relapse-free survival and 64.8% v. 87.1% for total survival, respectively (P less than 0.03). By contrast, in patients with stage IV disease the extent of mediastinal involvement did not affect results. Nonetheless, the frequency of intrathoracic relapses was higher (26.7%) in patients given chemotherapy alone compared with patients treated with combined modality (11.5%).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Third-line salvage chemotherapy in Hodgkin's disease.

CEP (CCNU, etoposide, and prednimustine) was tested as third-line chemotherapy in 40 patients resistant to both MOPP and ABVD. The observed response rate (complete remission, 35%, and partial remission, 25%) is encouraging. Treatment was generally well tolerated and all acute side effects were reversible.

Adolescent↗