[Preliminary study of phase I of bleomycin, a new anti-tumor drug].
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Biomedical subjects
Publications and source records attributed to S Monfardini.
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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.
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.
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.
Thirty-four consecutive patients with stage III testicular carcinomas were treated with vinblastine, 8 mg/m2 given in 2 fractions on day 1 and 2, followed by continuous intravenous administration of bleomycin, 15 mg/m2 in 1000 cc of 5% glucose and distilled water over a 24-hour period for 5 successive days beginning on day 2. This cycle was repeated every 28-35 days as toxicity permitted. Complete remission occurred in 18% and complete plus partial remission in 79%. Only 2 of 22 patients with advanced abdominal disease achieved a complete remission. After cytoreductive surgery the complete remission rate was increased to 39%. Median survival of complete responders at 3 years has not been reached, and it has been shown to be significantly superior to that of partial (p less than 0.01) and nonresponders (p less than 0.01). Toxic effects consisted mainly in severe leukopenia, stomatitis, adynamic ileum and osteoarticular pain. One drug-related death due to sepsis with agranulocytopenic fever was observed. Probably because of different patient selection, this report could not reproduce the results reported by Samuels et al. with equivalent drug dosage, but it was confirmed that this regimen is able to achieve a high overall response rate and a prolonged median survival in complete responders. The consistent success of this aggressive combination in inducing a high percentage of partial responses has opened the way for a better definition of the role of surgery for the treatment of advanced testicular carcinoma at out Institute.
To identify the subgroups of patients with malignant non-Hodgkin's lymphomas who might benefit from prophylactic therapy to prevent CNS relapse, lumbar puncture was routinely performed among the other staging procedures from January 1976 to October 1979 in 76 patients with diffuse lymphomas. The study also takes into consideration 32 patients who came to out observation during the same period and who were studied with lumbar puncture performed in case of suspicious CNS involvement or along with other procedures during restaging the acquire further information on prognostic factors related to CNS involvement. Cerebrospinal fluid (CSF) cytology was positive in 3 of 76 patients studied with initial lumbar puncture; however, only 2 (2.6%) were asymptomatic. Within the group of 32 patients in whom lumbar puncture was performed during the course of the disease, all 17 patients with suspicious CNS involvement were found to have a positive CSF cytology with the exception of 1 patients with multiple focal involvement of brain parenchyma. Clinical signs of CNS involvement associated with CNS positivity were all found in patients with diffuse histology. In these patients bone marrow invasion or a leukemic picture was frequently associated with CNS relapse. In 47% of patients CNS disease developed while they were in clinical remission. In this series cranio-spinal irradiation associated with intrathecal chemotherapy provided the best results, even in survival was not primarily dependent upon the control of their CNS involvement but related to progressive systemic disease in other sites. On the basis of the clinico-prognostic parameters examined, some guidelines for early diagnosis and treatment of CNS lymphomatous involvement are provided.
A case of extensive bone marrow infiltration due to gastric cancer is reported. A 65-year old man with an acute episode of anemia (Hb 4.1 mg/dl) and dyspnea was admitted to the Medical Department of a general hospital. Bone marrow biopsy showed extensive paratrabecular infiltration of a poorly differentiated adenocarcinoma of gastric origin. The primary tumor in the stomach was confirmed, and the patient was referred to our Institute and treated with combination chemotherapy (FAMTX) for 6 cycles. Due to the disappearance of bone marrow infiltration, the patient was considered for curative resection of the primary gastric cancer. After 27 months the patient is alive and in clinical complete remission.
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.
BACKGROUND: The incidence of Central Nervous System (CNS) neoplasias ranges from 3.8 to 5.1 cases per 100,000 inhabitants. In the presence of recurrence, the treatment is problematic; chemotherapy is experimental, primarily because the response is palliative and of limited duration. MATERIALS AND METHODS: This article analyzes the new drugs that have been introduced for the treatment of these patients in recent years, the objective response, the TTP and the MST. RESULTS: The most encouraging results to date come from studies of temozolomide, which is one of the most active and best tolerated drugs in recent years. CONCLUSION: New approaches to chemotherapy treatment are necessary. Enrollment of patients into rigorous, well-conducted, clinical trials, both at tumor diagnosis and after tumor recurrence, will generate new information regarding investigational therapies and may offer improved therapies for patients with malignant gliomas.
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After review of the pertinent literature on pathologic findings associated with Interleukin-2 (IL-2) therapy for metastatic malignancies (melanomas, renal cell carcinomas), two autoptic cases are described with particular emphasis on the cardiovascular and pulmonary changes. The authors report on the occurrence of massive transmural acute myocardial infarct in a patient with metastatic cutaneous melanoma, treated with recombinant IL-2, who did not show atherosclerotic lesions of the coronary arteries. Conversely, myocardial lesions were not found in the other patient with metastatic renal cell carcinoma, treated with recombinant IL-2; he had severe generalized atherosclerosis and died of pulmonary causes. It is suggested that myocardial direct toxic effects of IL-2 associated with capillary leak syndrome may determine a myocardial infarct. It is concluded that IL-2 therapy is not contra-indicated in oncologic patients with atherosclerosis of the coronaries if they are carefully monitored.
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