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Biomedical subjects

S Monfardini

Publications and source records attributed to S Monfardini.

At least 19 recordsLinked to original sources

Adjuvant therapy for primary breast cancer in a female patient affected by autoimmune liver disease: does it cure breast cancer and primary biliary cirrhosis?

Polychemotherapy (CMF or CMF-like regimens) is the treatment of choice in premenopausal breast cancer patients with 1-3 positive nodes. In clinical practice, patients with abnormal biochemical tests of liver function are usually excluded from this potentially curative methotrexate-containing regimen in order to avoid worsening of hepatic damage. On the other hand, recent reports have shown a beneficial effect of methotrexate in a particular autoimmune liver disease such as primary biliary cirrhosis. We discuss the case of a female patient with breast cancer and primary biliary cirrhosis whose biochemical tests of liver function and the titer of antimitochondrial antibody persistently improved after treatment with 3 cycles of CMF. In conclusion, we suggest that the CMF regimen is potentially useful in patients with breast cancer and primary biliary cirrhosis.

Antineoplastic Combined Chemotherapy Protocols

Phase II study of weekly 4'-epidoxorubicin in patients with metastatic squamous cell cancer of the cervix: an EORTC Gynaecological Cancer Cooperative Group Study.

In this study 24 patients with metastatic cervical cancer were treated with a weekly bolus injection of 4'-epidoxorubicin at a dose of 12.5 mg/m2. All patients were followed until disease progression. Toxicity was generally absent or very mild. Only 1 patient (4%) had a partial remission lasting 23 weeks and 9 patients (38%) had stable disease with a median duration of 13 weeks (range 7-36). 4'-Epidoxorubicin at this dose and schedule is not active in metastatic squamous cell carcinoma of the cervix.

Adult

Clinical classification and survival in chronic lymphocyte leukemia.

Sixty-one consecutive patients with chronic lymphocytic leukemia (CLL) treated at the Istituto Nazionale Tumori of Milan from September 1962 to August 1976 were classified according to the staging system of Rai et al. (16). Analysis of this series showed the following median survival (in months) from diagnosis: stage 0-I, 73; stage II, 44; stage III-IV, 32. In 11 patients without peripheral palpable adenopathies, the lymphangiogram showed abnormal retroperitoneal lymph nodes. Therefore, the initial stage was changed from 0 to I in 5 cases. The median survival for the entire series was 50 months. Patients with "indolent" disease had a median survival of 52 months, while in patients with "active" CLL, the median survival was 32 months. Both sex and age were shown to be poor predictors of survival. Increased duration of survival was observed in patients with less compared to those with more than 30,000 lymphocytes/mm3 (66 versus 41 months). The method of staging proposed by Rai et al. and utilized to classify this series at the time of diagnosis was confirmed to be a reliable predictor for survival.

Adult

Combined surgery and chemotherapy for retroperitoneal metastases of testicular carcinomas other than pure seminoma.

The results of treatment in 210 patients with testicular carcinomas other than pure seminoma are analysed. Patients with negative retroperitoneal nodes had a very good prognosis following lymph node dissection alone. Patients with positive nodes did much better after adjunctive chemotherapy than after post-operative irradiation. Patients with advanced disease showed significant improvement with intensive chemotherapy combined with surgery. Presently retroperitoneal lymphadenectomy combined with intensive chemotherapy seems to be the treatment of choice for metastatic testicular carcinomas.

Bleomycin

Controlled study with BCNU vs. CCNU as adjuvant chemotherapy following surgery plus radiotherapy for glioblastoma multiforme.

From September, 1972 to December, 1976, 102 consecutive patients operated on for glioblastoma multiforme were randomized, after total or subtotal tumor resection, to receive irradiation alone, irradiation plus BCNU or irradiation plus CCNU. BCNU and CCNU adjuvant chemotherapy was repeated every 6--8 weeks as long as the patients remained in complete remission. Patients were comparable for median age, type of surgery, and histological grade III and IV. Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups. The percent of optimal dose administered was 96% for BCNU and 93% for CCNU. In the group treated with radiotherapy alone (32 cases) the median survival was 10.5 months, while in the groups treated with BCNU (34 cases) and CCNU (36 cases) the median survival was 12 and 16 months, respectively. Both relapse-free (P = 0.05) and total survival (P = 0.03) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery. Present results show that in resectable glioblastoma multiforme, a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy. The cure rate was not improved.

Brain Neoplasms

Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas.

In stage IV non-Hodgkin's lymphomas, CVP (cyclophosphamide, vincristine, and prednisone) was randomly compared to ABP (adriamycin, bleomycin, and prednisone). Of 62 patients entered into the study, 57 (CVP 27, ABP 30) were considered evaluable for comparison. In patients with liver and/or marrow involvement a second biopsy was performed to define complete remission (CR). CR occurred in 48% of patients treated with CVP and in 50% of those given ABP. The median duration of CR was 10.5 and 20.5 months, respectively. The difference is not statistically significant. Also, the survival of complete responders was not significantly different between the two treatment groups. After cross-over, secondary treatment with CVP produced an overall response rate of 40% (six of 15), compared to 50% (six of 12) obtained with ABP. In the ABP group, four patients developed a reversible interstitial penumonia. In two other patients, cardiomyopathy (fatal in one) was observed. In conclusion, although complete remission was similar in both groups, cumulative toxicity occurred in few patients given ABP. However, this combination could represent an effective alternative treatment to be used either in CVP failures or sequence with CVP.

Adolescent

Non-cross-resistant combinations in stage IV non-Hodgkin's lymphomas.

Two triple-drug combinations (cyclophosphamide, vincristine, and prednisone [CVP] and adriamycin, bleomycin, and prednisone [ABP]) were randomly tested in 57 consecutive patients with pathologic stage IV non-Hodgkin's lymphoma. No statistical difference was observed in the incidence of complete remission (CR) (48% vs 50%), median duration of CR (10.5 vs 20.5 months), and survival. CR correlated positively with survival. After crossover for progression or relapse, no cross resistance was detected between the two combinations (CR plus PR = 40% for CVP and 50% for ABP). In a subsequent prospective study CVP and ABP were sequentially alternated in an attempt to improve the incidence and duration of CR. In the first 32 evaluable patients CR was produced in 50%. The findings are still preliminary.

Adolescent

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

Combination chemotherapy and radiotherapy in non-Hodgkin's lymphomata.

The results obtained with intensive chemotherapy and intensive chemotherapy plus radiotherapy in non-Hodgkin's lymphomata are reported. A quintuple drug regimen (mechloretamine, adriamycin, bleomycin, vincristine and prednisone) in histiocytic lymphomata (Stage III and IV) yielded complete remissions in 53% and complete plus partial remissions in 77%. These figures were 44% and 64% respectively in lymphocytic lymphoma. In Stage III complete responders after combination chemotherapy were subsequently irradiated (involved field irradiation). The median duration of complete remission after completion of radiotherapy was 9-5 months in histiocytic and 12-0 months in lymphocytic lymphomata. At 2 years actuarial survival in Stage III and IV was better in patients with the lymphocytic type and with nodular pattern than with histiocytic and diffuse patterns. A more recent trial compares, in Stage IV patients, cyclophosphamide, vincristine and prednisone (CVP) versus adriamycin, bleomycin and prednisone (ABP). Although the number of evaluable patients is still limited, there appears to be no difference in the response rate between CVP and ABP. In Stages I and II, 6 cycles of CVP were given as adjuvant treatment after radiotherapy. At the present moment, there is no statistical difference in the relapse rate between the group of patients treated with radiotherapy alone and that with radiotherapy plus CVP.

Antineoplastic Agents

[Long-term results and planning of therapy of seminal tumors of the testis].

The paper retrospectively reviews the modalities and the long-term results of treatment of 200 consecutive patients with pure seminoma and of 125 patients with testicular carcinomas admitted to the Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan from 1929 to Jan 1973. Radical orchiectomy with high ligation of the spermatic cord at the internal inguinal ring was performed in all previously untreated patients. Those who had had a scrotal operation performed elsewhere were radically reoperated upon. Lymphography and cobalt 60 telecurietherapy were introduced in 1960 and new treatment plans were employed for the irradiation of the deep lymphnodes. Since 1968 all operable carcinomas have undergone bilateral retroperitoneal lymphadenectomy and since 1964 all patients with advanced disease have been treated with chemotherapy (single agent or combination). Survival rates were calculated by the actuarial method. The new treatment modalities proved to be significantly superior to the old ones. In pure seminoma a 92% cure rate was obtained in NO patients after prophylactic irradiation of retroperitoneal nodes (2,500-3,000 rad in 3 weeks). In NI-3 patients the cure rate was as high as 75% after radical irradiation of retroperitoneal nodes (3,500-4,000 rad in 4 weeks) as well as prophylactic irradiation of mediastinum and both supraclavicular fossae. Extended radical radiotherapy (combined with chemotherapy in some patients) cured 2/6 N4 and 3/8 M1 patients. According to the old modalities of treatment, figures were respectively 72% in NO cases, 40% in N1-3 and 0% in N4 and M1 patients. In carcinomas, the cure rate after retroperitoneal lymphadenectomy was 91% in N--patients and 47% in N+ cases. In N+ patients post-operative radiation was also performed (4,000-5,000 rad in 5 weeks). After radiotherapy alone (without lymphadenectomy) the rates were 62% in NO and 28% in N1-2 patients. In primary inoperable patients (N3-4 and M1) chemotherapy, with or without radiation, significantly prolonged the survival rate. It is concluded that radiotherapy is the treatment of choice for pure seminoma and in N4 and M1 cases a full course of chemotherapy must be combined with extensive irradiation. Retroperitoneal lymphadenectomy is mandatory in all operable cases of testicular carcinoma while adjuvant chemotherapy may further improve the prognosis in N+ cases. For inoperable carcinomas chemotherapy (plus radiotherapy) is the treatment of choice. The new multiple drug regimens are providing encouraging results.

Adolescent

[Study of 12 cases of non-Hodgkin's lymphoma of the testicle (author's transl)].

Twelve consecutive cases of non-Hodgkin's lymphomas with initial testicular involvement have been considered in this retrospective evaluation. In 801 cases with referred for treatment to the Istituto Nazionale Tumori of Milan from 1962 to 1974 evidence of initial testicular involvement was observed in 1,4% of cases. Of the whole group of testicular tumors treated in our Institute only 3% were classified as non-Hodgkin's lymphomas. Six out of 12 patients with stage I (2 cases) and II (4 cases) diseases were treated with Cobalt therapy to the retroperitoneal nodes. Only one patient remained free of disease after radiotherapy. Three patients relapsed after primary irradiation and six patients classified as stage IV were treated with chemotherapy. Patients receiving combination chemotherapy had in general a better quality of response and a larger, but not significantly different, survival, compared to patients given simple agent sequential chemotherapy. Since the differential diagnosis between testicular lymphomas and seminomas may cause some difficulties and therapeutic implications are different, clinicians should be alert to this problem: in our case series testicular non-Hodgkin's lymphomas was the most frequent non-germinal tumor of the testicle.

Adolescent

[Controlled pilot study with combination chemotherapy in testicular carcinomas (author's transl)].

In 24 previously untreated patients with advanced testicular carcinoma, the combination of adriamycin, vincristine and methotrexate (AVM) was tested in a prospective randomized study against a combination of non-cross resistant drugs including vinblastine, bleomycin and mithramycin (VBM). Complete and partial (greater than 50%) remission was observed in 4 out of 13 patients treated with AVM and in 3 out of 11 given VBM. In one patient receiving AVM and in two patients treated with VBM, the response at the level of previous inoperable retroperitoneal metastatic lymph nodes allowed a subsequent radical lymph node dissection. After cross-over a partial response for 6 months was obtained in only one patient treated with VBM while none was observed in 4 patients receiving AVM. Both combinations were well tolerated. However, their therapeutic activity seems to be definitely lower with respect to treatment with vinblastine followed by continuous infusion with bleomycin.

Antineoplastic Agents

[The out-patient clinic for medical oncology treatment. Experience at the Istituto Nazionale Tumori of Milan (author's transl)].

The possibility to administer chemo-hormone- and immunotherapy on an out-patient basis has greatly increased because of the progress reached in the management of the out-patient departments. The improved knowledges on tossicological, pharmacodynamic and therapeutic data as well as the advent of the cyclic schedules determined the feasibility of medical treatments even when they are combined with surgical and/or radiotherapeutic modalities. To the patient, the possibility to be carefully and effectively treated on out-patient clinic, renders more acceptable, both from a psychologic and economic point of view, even a prolonged combined treatment. On the same time, also the Institutions have some advantages both on their organization (a shorter median stay in hospital and consequently a reduced waiting list) and for their scientific program (increased number of patients who can be treated according to a therapeutic program, possibilities to obtain statistically valuable information on the treatment program of a given disease and on the knowledge of its natural history). The last five year increasing activity of the Out-Patient Clinic for Medical Oncology Treatment of the Istituto Nazionale Tumori of Milan is illustrated in Text-figure 1, while Text-figure 2 represents its actual organization; this is obviously of a multidisciplinary type, both on its diagnostic and therapeutic phase. Table 1 shows the activity carried out in 1975; it is noteworthy that 2,570 patients have been followed, thus accounting for a total of 20,164 medical examinations and/or intravenous drug administrations. Table 2 presents the incidence of the different types of neoplasia followed in the out-patient department: the large majority was represented by breast cancer (40%); followed by malignant lymphomas (31.5%) and pediatric tumors (7.5%). During 1975, 22 therapeutic protocols have been applied, 10 of which (table 4) required an initial hospitalization and 12 (table 5) could be entirely carried out in the out-patient department. As shown in Table 6 chest x-rays accounted for 52% and skeletal survey for 18% of the 11.906 radiological examinations. Table 7 shows the number of off-hand required radiological reports carried out for patients not geographically accessible who, in one signle day, could have their radiological, and medical examinations as well as their hemogram and treatment performed. A total 467 scintiscans have been required, 86% of which of the liver (table 8). The hemato-pathology unit counted out about 16,000 hemograms with platelets (table 9). The hemograms were always performed within 1-2 hours with immediate communication of the counts to the out-patient department. In order to modify clinical situations which were deteriorated because either of the disease or of the treatment 358 blood units were transfused.

Academies and Institutes