[Sensitivity of cancers of the endocrine pancreas to chemotherapy].
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Biomedical subjects
Publications and source records attributed to C Jacquillat.
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We report here two randomized prospective clinical trials of adjuvant treatment in the management of primary malignant melanoma of Clark's level III, IV or V. All patients had curative resection of the primary tumor. In the first trial, 117 patients were randomized between control (surgery alone) systemic chemotherapy and intraarterial chemotherapy. Intraarterial chemotherapy consisted of DTIC 80 mg/m2 + 8 days prior to surgery. Systemic chemotherapy consisted of courses of vinblastine (6 mg/m2), thiotepa (6 mg/m2), rufocromycine (60 microgram/m2), methotrexate (15 mg/m2) on day 1, and procarbazine (30 mg/m12 X 7 days. Courses were repeated every 2 weeks X 6, then every 4 weeks X 15. Twenty-two of 55 patients relapsed in the control group versus 22 of 67 in the chemotherapy group (NS). For male patients, the difference in disease-free survival was significant (P less than 0.005, log rank test), though not in women. In the second trial, 352 patients were entered from July, 1976. Men were randomized between chemotherapy and chemoimmunotherapy. Women were randomized between surgery alone and chemoimmunotherapy. Chemotherapy was identical, except for the addition of DTIC (300 mg/m2) for each course. Immunotherapy consisted of BCG every 4 weeks and C. parvum every week. Immunotherapy seemed to be of no additional benefit.
Complications after treatment of Hodgkin's disease are a good model to evaluate the long-term cost of combined chemo- and radiotherapy. Secondary malignancies and mainly acute myelocytic leukemias are the main complications. The 35 of 1,889 cases reported represent increased risk by factor 129. Often preceded by a leukemic phase, they are of poor prognosis. Solid tumors are increased by factor 2.8. They may occur in patients treated by prolonged chemotherapy with alkylating agent without radiotherapy. In seven of 31 patients, solid tumors appeared in the irradiated area. Sterility in young males was present during the first year, though some recuperation was observed thereafter. Better adjustment of treatment to individual risk, to drug sensitivity, and active combinations devoid of alkylating agents are required to reduce the rate of these complications.
Burkitt's-type leukemias have specific cytologic, immunologic, and cytogenetic characteristics. Initial symptomatology frequently includes abdominal tumors and initial CNS involvement. Despite intensive treatment including high-dose cyclophosphamide, prognosis remains poor in most patients because of failures to achieve complete remission (CR) or because of early relapses, especially CNS relapses. Class III acute lymphoblastic leukemia in children is defined by the presence of two or more unfavorable parameters and recent progress has been achieved by intensive therapy. Cox's multifactorial analysis allows improved discrimination. A phase I protocol for increased-risk leukemias, including testis preventive irradiation and monthly reinductions without continuous maintenance for the first 6 months of CR, seems promising.
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We have studied the children born of leukemic parents who treatment had stopped. In total, 8 women (3 acute myeloblastic leukemias and 5 acute lymphoblastic leukemias) who gave birth to 11 children, and 6 men (all with acute lymphoblastic leukemias) who fathered 12 children were studied. Of these 23 children, two have a severe congenital malformation, one congenital hypopituitarism associated with mid-line defect, and one laparoschisis, and also two benign abnormalities were observed. The children with abnormalities had a leukemic mother, whilst no leukemic father had an abnormal child. It is well known that the toxic effect of chemotherapy is different in the male and the female gonad. These results are compared to those in the literature, and at present it appears difficult to form a clear opinion on the delayed teratogenic effect of chemotherapy. Fecundity and the risk for future generations are unknown. The opening of an international registry would be useful.
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The prognosis of non-seminomatous carcinoma of the testis has been revolutionized by the introduction of chemotherapy for both advanced and localised forms of the disease. In the last 15 years, 41 cancers of this type (13 Stage I, 16 Stage II and 12 Stage III) have been treated in our Department. All Stage I cancers received postoperative chemotherapy comprising Velbé, Thiotepa, Rufocromomycine and Methotrexate and all are in remission with an average follow-up period of 8 years. Five Stage II had this protocol, the II others had 3 cycles of PVB (a pulmonary recurrence in one case was treated with 3 further cycles of PVB +/- Adriamycin) and curative surgery. This survival is 100 p. 100 with a follow-up ranging from I to II years. Six patients had post-chemotherapy surgery which was always negative. The combination used in Stage I was also used in 8 Stage III patients; there were 7 failures despite falling back on PVB in 4 cases; the 8th case in still is remission after years' follow-up. The PVB protocol was used recently in 4 other cases with 2 complete remissions, one death in remission during thoracotomy (shocking) and one death from aplasia after the first cycle. This gives a 24 p. 100 5 year survival but only a third of Stage III patients had PVB from the outset. A review of the literature and our own experience suggest that curage and chemotherapy are no longer indicated in Stage I; curage is only proposed after 3 cycles of PVB in Stage II cases with a poor prognosis; 4 to 6 cycles of PVB are recommended in Stage III with secondary surgery if indicated. Maintenance therapy does not seem to be necessary.
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Survivals of two series of CLL patients (99 from a retrospective series and 196 from a prospective series) were studied separately. The three main staging systems (Rai, Binet, Rundles) agreed well, but as far as survival is concerned, too many stages are defined. The authors performed a Cox multivariate analysis of survival in order to isolate important prognostic factors at diagnosis and to use them to build a simple three-stage classification. Thrombopenia and anemia appeared as the most important risk factors. Among the nonanemic and nonthrombopenic patients, the number of involved areas was clearly related to prognosis in the authors' two series. This study allowed the authors to propose a new classification in three prognostic groups. Group C: anemia (Hb less than 10 g) and/or thrombopenia (platelets less than 100,000/mm3); about 15% of the patients; median of 2 years. Group B: no anemia, no thrombopenia, three or more involved areas (counting as one each of the following: axillary, cervical, inguinal, lymph nodes, whether unilateral or bilateral, spleen and liver); about 30% of patients; median of 7 years. Group A: no anemia, no thrombopenia, less than three involved areas; about 55% of patients; the survival of this group does not seem different from that of the French population of the same age and sex distribution. This three-stage classification only requires clinical examination and routine hemogram, has a good prognostic value which was confirmed on the series of Montserrat and Rozman (146 patients), and should therefore be helpful in planning new clinical trials.
Eighty-five patients with nodular lymphoma diagnosed between 1968 and 1975 were followed up for long periods and were treated by either conventional methods (local radiotherapy and single drug chemotherapy) or by more intensive therapeutic regimens, such as initial combined M.O.P.P. therapy and maintenance treatment with chlorambucil with or without further courses of M.O.P.P. Long-term follow-ups have brought to light some interesting points concerning the prognosis. Dissemination of the disease and large-cell histological pattern were, as already known, unfavourable factors. Neither age nor sex, nor bone-marrow involvement seemed to have any influence. Obtaining complete remissions improved the prognosis, but intensifying the initial and maintenance treatments proved disappointing: the survival rate remained the same, and the incidence of drug induced leukaemias was high. Indeed, relapses appeared to be less responsive to treatment when the patient had initially received multiple chemotherapy. However, in view of the high death rate of the disease (one-third of the patients in this series died within the first 5 years), trying new therapeutic regimens in the hope of obtaining better results, as has been done in Hodgkin's disease, would be fully justified.
This is a review of the progress achieved in the treatment of acute lymphoblastic leukaemia, based on a series of 1580 children treated in Prof. Jean Bernard's unit, Paris, from 1956 to 1976. The children are retrospectively divided into three prognostic classes and five therapeutic categories. The benefits obtained from successive additions to the therapeutic armentarium during that period are conspicuous in all classes and categories and particularly striking in children with poor initial prognosis. The role of each component of the therapeutic measures applied is discussed.
In a retrospective study covering the years 1963-1976 and involving 1 094 patients, 33 solid tumours were found to have occurred in 31 patients previously treated for Hodgkin's disease. The mean actuarial risk at 10 years of developing a second solid tumour is estimated at 5.4%, but the incidence varies according to the treatment applied, being 10.9% in patients under combined chemotherapy and 1.8% in patients under single-agent chemotherapy (p less than 0,04). This would confirm the role of chemotherapy in the development of second solid tumours, the course of which does not seem to differ from that of indentical primary tumours. The overall risk of having secondary solid tumours after treatment for Hodgkin's disease is 2.4 times higher than in normal control population (p less than 0.01).
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