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Biomedical subjects

G Bonadonna

Publications and source records attributed to G Bonadonna.

At least 325 records · Page 18Linked to original sources

Response and survival in advanced breast cancer after two non-cross-resistant combinations.

A prospective study with two cytotoxic combinations (cyclophosphamide, methotrexate, and fluorouracil (CMF), and adriamycin plus vincristine (AV)) was carried out in 110 patients with advanced breast cancer. There was no significant difference between the treatment groups in the response rate after primary treatment, the median duration of response, and the median survival. In both groups responders survived for longer than non-responders. Secondary treatment after crossover for progression or relapse resulted in response rates of 35% for AV and 20% for CMF. Toxicity was mainly represented by reversible haemosuppression. These results are comparable with those obtained with other multiple-drug regimens, and combination chemotherapy alone seems to have reached a plateau in its capacity to control disseminated breast cancer.

Antineoplastic Agents↗

Combination chemotherapy as an adjuvant treatment in operable breast cancer.

Prolonged cyclic combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil was evaluated as adjuvant treatment to radical mastectomy in primary breast cancer with positive axillary lymph nodes. After 27 months of study, treatment occurred in 24 per cent of 179 control patients and in 5.3 per cent of 207 women given combination chemotherapy (P less than 10(-6)), the advantage appearing statistically significant in all subgroups of patients. Patients with four or more positive axillary nodes had a higher per cent of relapses than those with fewer nodes. The initial new clinical manifestations occurred in distant sites in 81.5 per cent of relapsed patients. Long-term chemotherapy produced an acceptable toxicity, thus allowing the administration of a high percentage of drug dosage. These results should be considered with caution, since, at present, the effect of this therapy on survival and possible long-term side effects remain unknown.

Adult↗

Natural history and survival of inoperable breast cancer treated with radiotherapy and radiotherapy followed by radical mastectomy.

This retrospective study evaluates the time and site of relapse as well as the median survival of 454 consecutive patients with T3-T4 Nx Mo breast cancer treated with radiation therapy from 1968 to 1972. Radiotherapy was delivered with kilovoltage to the first 221 patients and with cobalt to 233 patients, respectively. A group of 133 selected patients was subjected to radical mastectomy 6-8 weeks after completion of the irradiation. The incidence of first relapse was 45% within the first 18 months from starting radiotherapy. The incidence of relapse was higher in presence than in absence of regional adenopathy, with no statistical difference between T3 and T4. Inflammatory carcinoma showed the highest percent of relapse during the first 12 months (48%). The relapse rate appeared independent from type of irradiation. The site of first relapse occurred more often (68%) in areas distant from irradiation fields. Sterilization of both primary tumor and regional nodes was obtained only in 10% of patients. The median survival for the whole series was 2.5 years, with no significant difference between roentgen therapy (3 years) and cobalt (2.5 years). Unfavorable survival was directly related to the presence of regional adenopathies (2.3 years), especially in the supraclavicular fossa (1.4 years) and of inflammatory carcinoma (1.2 years). Patients treated with radiotherapy followed by surgery showed a median survival of 3.9 years compared to 2.1 years for those given only irradiation. The importance of sequentially combining chemotherapy with radiotherapy is discussed.

Breast Neoplasms↗

Comparative evaluation of three combination regimens for advanced malignant melanoma: results of an international cooperative study.

The therapeutic results of a controlled study with three multiple-drug regimens (regimen A: DTIC, vincristine, BCNU; regimen B: DTIC, vincristine, hydroxyurea; and regimen C: DTIC, actinomycin D, BCNU) in a total of 274 evaluable patients with advanced malignant melanoma are reported. CRs were significantly more frequent (P less than 0.01) in regimens A (9.3%) and C (16.4%) compared with regimen B (1.1%). No significant difference in terms of CR plus PR was detected among the three regimens. In all regimens a higher number of CRs plus PRs was seen in patients with soft tissue metastases only, compared with those who had visceral involvement. In all three regimens patients achieving CR showed a longer duration of response and survival in comparison with patients achieving PR. The incidence of brain metastases was neither lowered nor delayed by the presence of BCNU in regimens A and C.

Adolescent↗

Treatment of residual neoplastic disease in solid tumours.

Contemporary clinical research is actively engaged at the conquest of residual neoplastic disease. The preliminary results of combined treatment modalities for osteogenic sarcoma, Ewing's sarcoma, rhabdomyosarcoma, breast cancer, malignant melanoma and Hodgkin's disease have shown a significant decrease in the incidence of distant metastases. In some neoplasias the decreased relapse rate was associated to improved survival. Since the problem of long-term carcinogenesis does exist, the use of prolonged adjuvant chemotherapy, at present moment, is best limited to patients at high risk of early relapse when treated only with local or local-regional modalities.

Breast Neoplasms↗

Sequential laparoscopy and laparotomy combined with bone marrow biopsy in staging Hodgkin's disease.

In a series of 121 unselected, previously untreated patients with Hodgkin's disease staging laparoscopy combined with needle bone marrow biopsy detected the presence of extranodal disease in the liver or marrow or both in 9% of the patients. A spleen biopsy yielded positive findings in 13%. Subsequent laparotomy with open marrow biopsy performed in 110 patients with negative liver and marrow findings from the first combined procedure revealed the presence of extranodal hepatic lymphoma in two additional spleens. Surgical marrow biopsy was always interpretey. Although devoid of major complications, biopsy of the spleen is not recommended as a routine procedure in staging laparoscopy. This prospective sequential study confirms that laparoscopy plus needle marrow biopsy is a useful, rapid, safe, and economic procedure to establish stage IV disease in the large majority of patients with nodal involvement. Considering the recent more extensive use of chemotherapy for intermediate stages of Hodgkin's disease, our findings suggest that laparotomy with splenectomy needs a critical re-evaluation as a routine staging procedure for patients with no overt extranodal lymphoma.

Biopsy, Needle↗

Combination chemotherapy with DTIC (NSC-45388) in advanced malignant melanoma, soft tissue sarcomas, and Hodgkin's disease.

The results of three controlled studies with multiple-drug regimens which included DTIC are reported for advanced melanoma, soft tissue sarcomas, and Hodgkin's disease. In malignant melanoma, no statistical difference was observed between (a) DTIC, BCNU, and vincristine, and (b) DTIC, BCNU, and actinomycin D in terms of response rate, median duration of response, and survival. In sarcomas, the combination of adriamycin and DTIC produced a higher incidence of complete plus partial responders when compared to cyclophosphamide, vincristine, and methotrexate. However, no significant difference was seen in the median duration of response or survival. In Hodgkin's disease, a new four-drug combination including adriamycin, bleomycin, vinblastine, and DTIC (ABVD) produced an incidence of complete remissions and a median duration of response comparable to that achieved with mechlorethamine, vincristine (Oncovin), predinisone, and procarbazine (MOPP). Preliminary data indicate that ABVD is not cross resistant to MOPP. It is concluded that DTIC can be successfully and safely employed in combination with conventional agents in susceptible neoplastic diseases.

Antineoplastic Agents↗

Laparoscopy and laparotomy combined with bone marrow biopsy in staging Hodgkin's disease.

The relative merits of laparoscopy with liver and spleen biopsy and staging laparotomy were studied in 91 unselected patients with Hodgkin's disease. Laparoscopy with liver and spleen biopsy were combined with needle biopsy of the bone marrow and laparotomy was combined with open bone marrow biopsy. In 65 untreated patients six out of seven with liver or marrow disease, or both, were shown to have extranodal lymphomas in these sites by laparoscopy plus needle marrow biopsy. Among 26 patients who had been treated this finding occurred in six out of 10 patients. Spleen biopsies during laparoscopy detected infiltration by lymphoma in 14 out of 37 (38%) patients with diseases spleens. Morbidity was higher after laparotomy than after laparoscopy. Laparoscopy produced abdominal bleeding secondary to splenic biopsy in two patients. All patients with Hodgkin's disease should be subjected to laparoscopy plus needle marrow biopsy before undergoing laparotomy.

Adolescent↗

Adriamycin plus vincristine compared to and combined with cyclophosphamide, methotrexate, and 5-fluorouracil for advanced breast cancer.

The preliminary results of a controlled study with two independent combinations in metastatic breast cancer are reported. The first combination (Therapy A: 41 patients) consisted of Adriamycin (ADM) and vincristine (VCR), while the second combination (Therapy B: 41 patients) included cyclophosphamide (CTX), methotrexate (MTX), and 5-fluorouracil (FU), designated "CMF." Both treatments were administered as intermittent cycles in patients previously untreated with chemotherapy. After eight cycles, responsive patients on Therapy A were crossed over to Therapy B to avoid the risk of cardiomyopathy. In both groups, crossover was carried out at the time of progression or relapse. In the group given ADM plus VCR, the dominant site of disease was in soft tissues in 56%, in viscera in 22%, and in bones in 22%. These findings were present in 51%, 24%, and 24%, respectively in the group started on CMF. The comparison of response after primary treatment in patients receiving a minimum of two cycles failed to show a significant difference between Therapy A and Therapy B (overall response 58% vs. 65%). When the response rate was calculated only in patients who had completed the first eight cycles of therapy, these findings were 87% and 93%, respectively. Three patients receiving treatment A (8%) AND 4 patients given Treatment B (10%) achieved complete remission. The highest incidence of response was observed for soft tissue lesions (70% vs. 76%). However, complete or partial bone recalcification was seen in 33% and 24%, respectively. The duration of response was found to be longer in patients who crossed over to CMF after eight cycles of ADM plus VCR, as compared to those started and continued on CMF. No cross-resistance was observed after crossover for progressive disease. Both incidence and degree of side effects were found acceptable, and no drug-related death was seen. Virtually all patients were treated on an outpatient basis.

Antineoplastic Agents↗

Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP.

This paper reports the preliminary results of a controlled study randomizing MOPP vs. a new four-drug combination (ABVD) in advanced Hodgkin's disease. ABVD consists of 6 cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide. The purpose for designing this new combination was two-fold: to compare the efficacy of ABVD with MOPP, and to demonstrate absence of cross-resistance between the two regimens. Of 60 patients entered into the study, 45 (MOPP25, ABVD20) are presently evaluable for the analysis of remission induction. No patient was previously treated with chemotherapy; 20% had relapsed after primary radiotherapy. Whenever possible, complete remission was defined also through rebiopsy of known organ involvement. Complete remission occurred in 76% of patients treated with MOPP and in 75% of those given ABVD, with no difference between the two regimens as far as stage (IIIB-IIIS and IV), histologic type, and prior irradiation were concerned. Crossover carried out for progressive disease or for relapse after initial remission showed absence of cross-resistance between MOPP and ABVD. Toxic manifestations after ABVD were in general well tolerated and reversible. The percent of optimal dose for each drug was as follows: adriamycin 87%, vinblastine 87%, bleomycin 96%, and imidazole carboxamide 96%. These preliminary results indicate that in terms of complete remission, ABVD could represent a successful alternative to MOPP to be used either in MOPP failures or in sequential combination with MOPP. However, the lack of long-term followup limits at the present time an adequate comparison between the two treatments.

Adolescent↗

Staging laparotomy in non-Hodgkin's lymphomata.

Staging laparotomy was performed in 106 selected untreated adults and in 6 children. In adults the histological pattern at initial biopsy was interpreted as nodular lymphoma in 33% and as diffuse lymphoma in 67%. Diffuse histiocytic was the most frequently observed histological subtype in the present series (54%). Diffuse undifferentiated lymphoma was noted in 2/6 children. Waldeyer's ring involvement was noted in 27% of adult patients. Systemic symptoms were present in 7%. Surgery detected occult lesions in 27% of patients (para-aortic nodes 3%, spleen 12%, liver 12%, coeliac nodes 15%, splenic hilar nodes 26%, mesenteric nodes 15%, gastrointestinal tract 1%, bone marrow 12%). The chance of detecting splenic and hepatic involvement was definitely higher in patients with nodal disease above and below the diaphragm in comparison with those with either supra-diaphragmatic or infra-diaphragmatic adenopathy. Lymphography yielded a 96% accuracy proving once more to be a sufficiently reliable diagnostic method. Staging laparotomy is a useful procedure in non-Hodgkin's lymphomata in order to gain information on the natural history and to plan treatment. It remains to be determined whether findings observed through surgical staging will lead to improved treatment and survival.

Adolescent↗