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PubMed1989

Treatment of advanced Hodgkin's disease.

MOPP chemotherapy was the significant breakthrough that improved the outlook for patients with advanced Hodgkin's disease. Results with alternating potentially non-cross-resistant drug combinations, including MOPP/ABVD, CAD/MOPP/ABV, and MOPP/ABV, are similar and seem to be slightly superior to those with MOPP alone. Limited adjuvant RT does not seem to add appreciably to the morbidity of chemotherapy, although its role in improving on results with chemotherapy alone has not been well studied in prospective, randomized, controlled clinical trials. There are two major challenges for the future. The first is to improve the outcome for advanced Hodgkin's disease patients, perhaps with more intensive chemotherapy and RT with use of cytokines such as the colony-stimulating factors or interleukin-1 or with rescue employing autologous bone marrow transplantation or both. The second challenge is to reduce the morbidity but not the effectiveness of treatment for advanced Hodgkin's disease patients without adverse prognostic factors.

Adolescent↗
PubMedDate not supplied

[Results of the treatment of patients with advanced Hodgkin's disease by the ABDiC and/or BVCPP protocols].

In 22 patients with phase IV of Hodgkin's disease refractory to treatment by the programmes MOPP and/or CVPP, and ABCD and/or BACOP, and in patients with recurrences after this treatment the ABDIC and/or BVCPP programmes were applied. In 5 cases this treatment was associated with radiotherapy. Complete remission lasting 30 months was achieved in one case. In 9 cases only clinical improvement was noted. Twelve patients failed to respond to this treatment. Ten patients died. The mean survival time of all patients from the beginning of treatment by ABDIC and BVCPP programmes to the end of the observation was 14 months, and the time from the diagnosis to the end of the observation was 69 months. The results of this treatment are not satisfactory.

Adult↗
PubMed1989

Response of cultured human cell lines from rhabdomyosarcoma xenografts to treatment with chloroethylnitrosoureas.

DNA interstrand cross-links are thought to be the cytotoxic lesion resulting from treatment of cells with the chlorethylnitrosoureas (CENUs). We showed in an earlier study that the resistance of xenografts of pediatric rhabdomyosarcoma to therapy with CENUs correlates with levels of O6-alkylguanine-DNA alkyltransferase. We now demonstrate a relationship between levels of the alkyltransferase and CENU-induced cytotoxicity and DNA-interstrand cross-link formation in two cell lines recently established from such rhabdomyosarcoma xenografts. Rh18 cells were derived from the HxRh18 xenograft line, which contains the alkyl-transferase and is relatively resistant to CENUs, and Rh28 cells were derived from the HxRh28 xenograft line, which lacks detectable alkyltransferase activity and is sensitive to treatment with the CENUs. In vitro, Rh28 cells were 5- to 6-fold more sensitive to growth inhibition by 1,3-bis(2-chloroethyl)nitrosourea than Rh18 cells. Extracts of Rh18 cells contained 3.8 units of the alkyltransferase per mg of protein, whereas such activity was undetectable in Rh28 cells, a unit of the alkyltransferase being defined as 1 pmol of [3H] methyl transferred from [3H]methyl-labeled DNA to protein. DNA interstrand cross-links, measured by alkaline elution 6 h after a 1-h pulse treatment with CENU, could not be detected in Rh18 cells but were found in the Rh28 line. The phenotypes of the parental xenograft lines defined by their alkyltransferase levels and by responses to CENU therapy of the mice have clearly been retained in the cultured cell lines, and as predicted, cross-link formation was inhibited in the alkyltransferase-containing Rh18 cells. These two new cell lines thus provide a useful model for studying the role of DNA repair in rhabdomyosarcoma resistance to these alkylating agents.

Animals↗
PubMed1989

Modulation of human lymphocyte O6-alkylguanine-DNA alkyltransferase by streptozotocin in vivo.

The ability to modulate DNA repair has been proposed as an effective method to overcome cytotoxic drug resistance in human tumors. However, no studies have shown that it is possible to achieve modulation of DNA repair in humans in vivo. This study analyzes modulation of O6-alkylguanine-DNA alkyltransferase, a DNA repair protein that protects cells from cytotoxic DNA adducts formed by nitrosoureas. Streptozotocin has been shown to inactivate the alkyltransferase in vitro and sensitize tumor cells to other nitrosoureas. Thus, we determined whether biochemical modulation of alkyltransferase activity could be documented in patients receiving therapeutic doses of streptozotocin and whether the modulation was specific to streptozotocin or occurred in patients undergoing treatment with other DNA-damaging agents as well. Normal peripheral blood lymphocytes were used to analyze modulation of the alkyltransferase. We found that lymphocyte alkyltransferase activity was significantly decreased 20 h after treatment with streptozotocin (500 mg/m2) or high dose 1,3-bis-(2-chloroethyl)-1-nitrosourea (350 mg/m2) but not after treatment with the other DNA-damaging agents or lower doses of 1,3-bis-(2-chloroethyl)-1-nitrosourea. A cumulative decline in lymphocyte alkyltransferase activity occurred with daily streptozotocin treatment, reaching 26 +/- 9% of control after the third day of treatment (P less than 0.0005). Thus, the alkyltransferase DNA repair protein can be modulated in vivo in humans given systemic drug treatment. While further studies are needed to document that biochemical modulation can be achieved in the target tumor in humans, this study supports the development of clinical trials using streptozotocin as a biochemical modulator of nitrosourea resistance in human malignancies.

Carmustine↗
PubMed1989

Efficiency of the radio-chemo-surgical. Treatment in cerebral astrocytomas.

This paper reports on the evaluation of 29 patients with I-st grade, 35 patients with II-nd grade astrocytomas and 145 patients with malignant astrocytomas (gr. III or IV) with a postoperative Karnofski index of minimum 60, treated with wide surgical resections, chemotherapy (CCNU 130 mg/m2 body surface) and irradiation with 60Co or conventional roentgen-therapy, in doses of 50-60 Gy, fractionated applied. The control group was formed by patients treated surgically and by postoperative irradiation: 5 with I-st and II-nd grade astrocytomas and 30 with malignant ones. Comparison of the results shows a median survival of 71.5 weeks for I-st grade, 66.5 weeks for II-nd grade and 44 weeks for high malignant astrocytomas treated only with CCNU, as against 150, 119 and respectively 73 weeks when chemotherapy was associated with irradiation with 60Co. The statistical differences between the results of radiochemotherapy and the cobalt-therapy applied alone were also very significant. The long-term survival: at 5 years for I-st and II-nd degree and at 1 and 3 year for malignant astrocytomas revealed the same superiority of the complex associated treatment (radio-chemo-surgical). No significant differences in survival were recorded in relation to age, sex and site in surgically treatable cases. However the infiltrative character of the tumors significantly aggravate the prognosis. It is concluded that association of chemotherapy with cobalt-therapy postoperatively brings about a statistical significant increase in survival as against postoperative chemotherapy or irradiation applied alone.

Adult↗
PubMed1985

Third-line salvage chemotherapy in Hodgkin's disease.

CEP (CCNU, etoposide, and prednimustine) was tested as third-line chemotherapy in 40 patients resistant to both MOPP and ABVD. The observed response rate (complete remission, 35%, and partial remission, 25%) is encouraging. Treatment was generally well tolerated and all acute side effects were reversible.

Adolescent↗
PubMed1989

[Various doses cisplatin combined with multi-drug chemotherapy of malignant solid tumors].

236 patients with various advanced malignant solid tumors treated by combined chemotherapy with routine doses of cisplatin (DDP) from 1980 to 1986 are presented. According to different doses of cisplatin everyday, the patients were divided into 4 groups: 1. 20 mg/day x4-5, 80 cases; 2. 30 mg/day x3-5, 91 cases; 3. 40 mg/day x3-4, 37 cases; 4. 50 mg/day x2-3, 28 cases. Each group was repeated for 3 weeks. The effect and toxicity were analysed and compared with 22 cases treated by single DDP in 1975. The response (CR + PR) rate was 39.2% in 194 evaluated patients. The response rate was similar in group 20 mg and single DDP (29.2% and 27.3%). The response rate was lower than that of group 30 mg, 40 mg, and 50 mg (43.4%, 42.4%, and 50%) (P less than 0.05). The remissions in various groups were not significantly different. The toxicity of combined chemotherapy was not severe. 91.1% of patients had nausea and vomiting. There was no statistical difference in the various groups. Bone marrow suppression was less in single DDP group than that of combined chemotherapy group, (P less than 0.05). DDP 30 mg-50 mg 1/d x5-3 was better than HD-DDP in some patients.

Adenocarcinoma↗
PubMed1989

Improved long-term survival in multiple myeloma. Finnish Leukaemia Group.

50 patients were treated for multiple myeloma with 5-drug combination chemotherapy between Jan 1979 and Feb 1980. After 8 years 12 patients (24%) were alive. The relative age-adjusted survival rate was 27%. The risk of death was constant during the follow-up, and active myelomatosis was still the main cause of death during the 8th yr. Thus the treatment is not curative. All 7 long-term survivors initially at stages II or III had at least a 75% response to the primary treatment. The other 5 patients were initially in an early stage (I) of their disease. Acute leukaemia has developed in 2 patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Surgical therapy of early rectal carcinoma.

Radical surgical resection is the "gold standard" treatment for rectal carcinoma. Results indicating that radiation therapy reduces the incidence of local recurrence and that combined modality radiation therapy and chemotherapy reduce the rate of local and distant failures, as well as improving survival, has produced interest in adjuvant therapy. Conservative procedures to treat rectal cancer are also gaining support because of reduced morbidity and mortality, avoidance of colostomy, and excellent survival figures in selected patients. The key phrase continues to be "in selected patients" because current data support conservative procedures as attempts for cure only in patients with small, histologically favorable tumors. The combination of local excision and adjuvant external beam irradiation holds promise for improved control of local disease in patients with early rectal carcinoma. Further prospective evaluation with long-term follow-up of patients with early rectal carcinoma treated with conservative procedures is needed to assess the efficacy of conservative management.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Evaluation of 5-year results of the scheduled treatment of lymphogranulomatosis in children].

A total of 186 children and adolescents aged 2.5 to 16 years with Hodgkin's disease were placed under observation. According to the accepted classification (Ann Harbour, 1971) they were divided into two groups. Exploration laparatomy was applied in the first group of the patients (n-103) as the final diagnostic stage in order to verify the pathomorphological stage of the process. In the second group (n-83) the clinical stage of the disease was only appraised. The pathological foci beneath the diaphragm were discovered, however, with the aid of ultrasonic tomography of the abdominal cavity, scanning with gallium-67 citrate, and computer-aided tomography. The latter technique was employed in case of controversies in the interpretation of the foci of lesion with the aid of the first two diagnostic methods. It is concluded that in view of the high tempo of the so-called silent generalization and dissemination of Hodgkin's disease in children, this condition should be regarded in childhood as a potentially systemic process. With such an attitude towards Hodgkin's disease in children it is advisable to abandon exploration laparotomy with splenectomy depriving the patient of the massive depot of humoral (B cell) immunity and creating the danger of an aggressive course of intercurrent infections in splenectomized children affected with Hodgkin's disease. In the choice of the initial treatment which provides the basis for obtaining the highest effect, preference should be given to polychemotherapy. It is indicated in the presence of "biological activity" of the process, general symptoms, generalization and dissemination of the process (stages III and IV), and in the presence of multiple foci in stage II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Vindesine, CCNU, high-dosage ara-C, and prednisolone (VINAP regimen) in the treatment of relapsing or refractory non-Hodgkin's lymphomas].

Results of second line chemotherapy schedules to treat refractory lymphoma have usually been poor. In this study we have treated 21 patients with advanced non-Hodgkin's lymphoma, usually heavily pretreated, with VINAP regimen. This original four drug chemotherapy combination included: Vindesine, 2 mg/m2 iv on days 1 and 2; CCNU, 40 mg/m2 oral on days 3 and 4; Cytosine arabinoside, 2.4 g/m2 iv on day 3 to 6 and methyl-Prednisolone, 80 mg/m2 on days 1 to 6. Sixteen patients (76%) showed response, including 5 (23%) who achieved a complete remission (CR). Eight patients achieved a partial remission (PR), and two patients obtained an objective response. Although the responses to VINAP regimen were dramatic and rapid in onset, usually they were of short duration except in cases of lymphosarcoma cell leukaemia. The median duration of response for patients with CR was 42 weeks and for PR 11 weeks. Toxicity was acceptable, including predictable myelosuppression, frequent mucositis and occasional polyneuritis. Neither central nervous problems nor conjunctivitis or dermatitis had been seen.

Adolescent↗
PubMed1978

An analysis of synergistic sensitization.

The molecular theory of cell survival predicts that a synergistic interaction on cell survival may be expected when DNA-damaging agents are used in combination with ionizing radiation. The synergism is expected to result from the interaction of DNA single-strand damage induced by the agent and single-stand breaks induced by the radiation. Mathematically this is expressed by an increase in the alpha coefficienty of the survival equation S = exp - (alpha D + beta D2), the beta coefficient remaining constant. Two examples of synergistic interaction with ionizing radiation are analysed, a chemical used in tumour therapy and ultra-violet light. The implication of this analysis for sensitization in radiation therapy are discussed.

Cell Survival↗
PubMed1989

[Indirect endolymphatic chemotherapy of patients with lymphoma].

Treated were 103 patients with malignant lymphomas (lymphogranulomatosis--87; non-Hodgkin lymphomas--16 patients). The treatment was complex including chemotherapy by means of endolymphatic administration of cyclophosphane, prospidin, methotrexate). The technique may be widely used and may be associated with other treatment methods. The efficacy of the method is substantiated and emphasized.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The impact of chemotherapy on small cell carcinoma of the bronchus.

Between 1971 and 1978, 140 cases of small cell anaplastic carcinoma of the bronchus were registered by a group of chest physicians in north Edinburgh. Sixty-five of these patients received specific treatment either with radiotherapy or cyclophosphamide and 75 patients were given treatment for symptoms only. Between 1979 and 1981 83 patients referred to the same physicians and pathologists were treated with combination chemotherapy (methotrexate, cyclophosphamide and CCNU) for 12 weeks. Overall median survival in the 1971 to 1978 group was two months with the actively-treated patients surviving for five months vs. less than one month for treatment of symptoms only. For the 83 patients treated with combination chemotherapy, median survival was nine months with 33 per cent alive at one year and 13 per cent at two years. Positive factors associated with prolonged survival included performance status at presentation and response to chemotherapy. This study demonstrates that the prognosis for the majority of patients with small cell carcinoma of the bronchus has improved significantly with the introduction of combination chemotherapy.

Adult↗
PubMed1987

[Global approach to the treatment of small cell bronchial cancers].

320 patients were included in a trial fo chemotherapy with cyclophosphamide/adriamycin/etoposide/CCNU. A first randomization tested the effect of acetyl-salicylic acid as an anti-aggregant agent. The second randomization studied the result of maintenance chemotherapy. Patients were treated by prophylactic central nervous system irradiation. The results are analyzed according to different prognostic factors such as age, performance status, histological pattern and the center.

Adult↗