Biomedical subjects
Publications and source records attributed to G Bonadonna.
Explore the source record for details and available documents.
In a randomized trial of adjuvant chemotherapy, immunotherapy, or immunochemotherapy, 761 evaluable patients with pathological Stage II cutaneous melanoma anywhere on the body or with pathological Stage I melanoma of the trunk (Clark's level 3 to 5) were studied by the World Health Organization International Melanoma Group. Wide local excision and excisional regional lymphadenectomy alone were performed in 185 patients and the results were compared with those of surgery plus chemotherapy with dacarbazine (in 192 patients), surgery plus immunotherapy with bacille Calmette-Guérin vaccine (in 203), and surgery plus chemotherapy combined with immunotherapy (in 181). The rates of disease-free survival and overall survival at 36 months were 30.4 +/- 8.3 per cent (mean +/- S.E.) and 41.6 +/- 10.0 per cent, respectively, after surgical treatment alone; 37.2 +/- 7.9 per cent and 46.5 +/- 8.3 per cent after surgery plus chemotherapy; 34.8 +/- 7.9 per cent and 48.7 +/- 8.7 per cent after surgery plus immunotherapy; and 33.6 +/- 7.9 per cent and 50.0 +/- 8.8 per cent after surgery plus a combination of chemotherapy and immunotherapy. None of the differences between groups was significant, and thus no effect of adjuvant therapy could be demonstrated in this study.
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
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.
Explore the source record for details and available documents.
Short-term results of adjuvant treatments of cancer have been reported all over the world with the specific aid of reducing the period required to determine the cure rate of a potentially curative treatment. While this motivation is important, short-term analyses are not totally unbiased and they require careful evaluation. The most peculiar aspect is that short-term results should properly predict long-term results. Therefore, a complete knowledge of the natural history of the disease under evaluation, an adequate number of patients, adequate follow-up of these patients, as well as a proper statistical analysis are essential to derive useful information from intermediate analysis. This paper attempts to point out these aspects and summarizes the experience of the Istituto Nazionale Tumori of Milan in two different adjuvant studies (breast cancer and non-Hodgkin's lymphomas).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
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.
One of the most serious complications of successful treatments for Hodgkin's disease is an increased incidence of acute nonlymphocytic leukemia (ANLL) and other malignancies. A retrospective analysis carried out on 1032 consecutive patients with Hodgkin's disease admitted to our Institute between 1965 and 1978 and treated with radiotherapy (RT) or chemotherapy or both modalities revealed that within 10 yr from initial therapy. ANLL was documented in 3% of patients, and over a comparable period of time 7.9% of patients developed other malignancies. ANLL was observed only in patients treated with chemotherapeutic regimens containing alkylating agents and/or procarbazine either alone (2.3%) or associated with RT (4%). Other second tumors were documented in patients given RT with or without chemotherapy. No second malignancies were observed in patients given ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) with or without RT. The incidence of ANLL was higher in patients given chemotherapy as salvage treatment upon relapse following primary irradiation (6.1%) compared to patients initially treated with combined modality (1.5%). The difference, however, failed to reach statistical significance. Since our analysis supports the evidence of a major role played by alkylating agents, procarbazine, and RT in inducing second malignancies, regimens not containing there drugs or their administration through treatments of different intensity warrant careful consideration.
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.
Thirty-two consecutive patients with metastatic malignant melanoma were treated with vinblastine, bleomycin, and cisplatin (VBD) chemotherapy. There were 29 evaluable patients; complete remission was observed in three and partial remission in five. No patient with visceral metastasis showed objective response. The 10-month survival rate of responders was significantly higher than that of nonresponders (57.1% vs 18.2%, P = 0.01); however, present results do not confirm that VBD is superior to other drug combinations for malignant melanoma.
The paper reviews new chemotherapy strategies for intermediate and advanced stages of Hodgkin's disease as well as the implications of recent biological concepts and mathematical models which appear useful in the interpretation and design of new treatments. The development and the application of the Adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) combination was based on critical reevaluation of benefits and limits of the mechlorethamine-vincristine-procarbazine-prednisone (MOPP) combination. The attempts to develop non-cross-resistant regimens, such as ABVD, arose intuitively at first from the desire to improve salvage treatment in MOPP-refractory patients; more recently, a theoretical framework for this approach has been proposed by Goldie and Coldman (Cancer Treat. Rep., 63: 1727-1733, 1979). The 5-year results achieved with different forms of salvage chemotherapy and with the cyclic delivery of non-cross-resistant combinations (MOPP and ABVD) can be explained largely by the assumption that drug-resistant mutants represent a major limiting factor in the cure of Hodgkin's disease, as well as of other neoplasms, by chemotherapy. The initial results from a prospective randomized trial indicate that the administration as front-line therapy of non-cross-resistant regimens is a logical and powerful strategic approach and therefore that it may constitute an important avenue of clinical research. Recent observations also emphasized the problem of the quality of life, since the administration of multidrug combinations not including alkylating agents and/or procarbazine appears to be associated with a decreased incidence of carcinogenesis and sterility. The departure from the standard practice of utilizing a single multidrug regimen for chemotherapy of Hodgkin's disease should be supported by sound research and controlled studies built on drug combinations of known efficacy and toxicity.
Explore the source record for details and available documents.
We studied the relation between an institution's degree of participation in a multicenter clinical trial and the quality of its participation. The quality of participation was judged on the basis of the percentage of patients entered into the trial who were in fact eligible, who were treated in accordance with the protocol, and for whom the appropriate forms were received. Those who satisfied these criteria were termed "valid" patients. Institutions were divided into two groups, "major participants" and "minor participants," according to the number of patients they entered in the trial. In a detailed analysis of a multicenter trial of chemotherapy for soft-tissue sarcoma, we found that major participants had a significantly higher percentage of valid patients than did minor participants (81 per cent vs. 39 per cent) and that the minor participants were actually detrimental to the study from both scientific and administrative viewpoints. These results suggest that institutions should not participate in multicenter studies unless they can enter some predetermined minimal number of patients per year.
The five-year results of a prospective randomised trial of radical mastectomy (179 patients) versus radical mastectomy followed by adjuvant chemotherapy (207 patients) were analysed. Chemotherapy consisted of 12 monthly cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Both relapse-free survival (controls 44.6%, CMF group 59.5%) and total survival (controls 66.2%, CMF group 78.4%) were significantly improved. The findings were related to the number of diseased axillary nodes and amount of drug administered, and were independent of CMF-induced amenorrhoea. Menopausal state alone appeared to affect the five-year results only when the amount of drug administered was not taken into account. Salvage treatment at first relapse failed to improve total survival in the controls compared with the CMF group. Acute toxic manifestations were moderate and reversible. Chronic organ damage and increased incidence of second neoplasms (controls 1.7%, CMF group 1.4%) were not observed. The multimodality approach to treatment of primary breast cancer is a new and important advance. This and other studies are continuing.
The medical records of women taking part in the first 2 prospective adjuvant CMF (cyclophosphamide, methotrexate, fluorouracil) programs were reviewed to evaluate the incidence of liver damage which could be attributable to prolonged methotrexate administration. In 802 evaluable patients abnormal liver studies occurred in 7 of 170 controls (4.1%) and 20 of 632 CMF-treated patients (3.2%). In 22 of 27 patients they were reversible, while the persistence of enzyme abnormalities in 2 patients treated with 12 CMF cycles was followed by the occurrence of viral hepatitis and osseous metastases, respectively. Adjuvant CMF was never discontinued in the presence of liver function abnormalities. In 22 women liver biopsies through laparoscopy were performed for various diagnostic purposes. They yielded an incidence of aspecific histologic changes (fatty metamorphosis, subcapsular fibrosis) which was similar between controls and CMF-treated patients. Present analysis failed to demonstrate a higher incidence of acute and/or chronic liver changes in patients treated with cyclical CMF compared to controls treated with surgery alone.
We retrospectively analyzed the role of the dose level of CMF (cyclophosphamide, methotrexate, and fluorouracil) in postoperative adjuvant chemotherapy for breast cancer and in chemotherapy for metastatic breast cancer. There was a clear dose-response effect, indicating that CMF was useful only when given in a full or nearly full dose (greater than or equal to 85 per cent of the planned dose). Those given adjuvant therapy with 12 cycles of CMF at this dose level had a five-year relapse-free survival of 77 per cent, as compared with 45 per cent of patients treated only with radical mastectomy (P = 0.0001). In contrast, a subgroup receiving less than 65 per cent of the planned dose had a five-year survival without relapses of 48 per cent and a five-year survival with relapses of 67 per cent. These results are similar to those observed in a control group. With each dose level, the results at five years were influenced by the number of axillary lymph nodes involved but not by menopausal status. Our findings indicate that it is necessary to administer combination chemotherapy at a full dose to achieve clinical benefit.