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PubMed1979

Malignant gliomas treated after surgery by combination chemotherapy and delayed radiation therapy. Part II. Tolerance to irradiation after chemotherapy.

34 patients operated on for malignant gliomas were successively treated by combination chemotherapy with VM26 and CCNU and conventional radiation therapy with an average dosage of 5,800 Rads, six months after surgery. The general and haematological tolerance of delayed irradiation after chemotherapy was satisfactory. Twelve patients developed neurological complications during or after irradiation. The complications were early in 10 cases, and delayed in 2. They were probably due to tumour growth in five cases, and secondary to irradiation in seven. In four of the seven cases the preradiation chemotherapy seemed to potentiate the radiation effect on the central nervous system.

Brain↗
PubMed1978

Experiments on the chemotheraphy of a transplantable glioblastoma in the rat, employing 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).

A glioblastoma was induced in BD-II rats by weekly i.v. injections of methylnitrosourea and transplanted intracerebrally in numerous passages. The take rate was 100%. For the experiments with CCNU, solid pieces of tumour were implanted into the right parietal region. The cytostatically treated animals lived significantly longer. The untreated tumour rats had an average survival time of 18 days (counted from the time of transplantation), and the rats treated with CCNU had an average survival time of 28 days. The median values were 19 and 28 days.

Animals↗
PubMed1978

Chemotherapy of malignant gliomas: comparison of the effect of polychemo- and CCNU-therapy.

Postoperative survival times of patients suffering from glioblastoma (astrozytoma III-IV) were compared in unselected groups receiving different forms of therapy: standard surgical therapy (16 cases, mean survival time 6.27 +/- 3.75 months), postoperative polychemotherapy (16 patients, survival time 8.96 +/- 4.97 months) or postoperative CCNU-monotherapy (24 cases, survival time 6.98 +/- 4.46 months). The mean survival time in the group receiving polychemotherapy was prolonged significantly when compared to the group with standard treatment. Survival time of the patient group treated with CCNU was not significantly increased. The results indicate that postoperative combination chemotherapy is more effective than CCNU monotherapy.

Adult↗
PubMed1977

Cerebral pseudocysts following chemotherapy of glioblastomas.

Three cases of pseudocysts following surgery and chemotherapy for glioblastomas are reported. Their clinical picture was similar, consisting of intracranial hypertension without primary modification of focal signs. CT scanning has been able to detect the cystic aspect and to eliminate a true tumour recurrence. Medical treatment (steroids or Mannitol) seems inefficient. Evacuation of the cyst is the only efficient method of treatment.

Adult↗
PubMed1990

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience.

In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours. In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.

Antineoplastic Agents↗
PubMed1990

Sacrosine- and prolinedithiocarbamate pretreatment increases the therapeutic efficacy of doxorubicin, methotrexate, teniposide, mitoxantrone or cyclohexylchloroethylnitrosourea in leukemia L1210.

The influence of different doses of the hydrophilic sarcosine- or prolinedithiocarbamate on the chemotherapeutic efficacy of doxorubicin, teniposide, methotrexate, mitoxantrone or cyclohexylchlorethylnitrosourea was evaluated in female B6D2F1 mice bearing leukemia L1210, implanted intraperitoneally. The simultaneous administration of these dithiocarbamates and the drugs used induced no increase of the therapeutic efficacy of the combinations compared to the corresponding dose of the drug and simultaneously applied saline. The results indicate that the subcutaneous pretreatment with sarcosine- or prolinedithiocarbamate increased the therapeutic efficacy of the drugs used compared to the corresponding monotherapy, in which saline was applied in the same interval as the dithiocarbamate and the antineoplastic agents. Sarcosine- or prolinedithiocarbamate applied alone did not influence leukemia L1210. The increase of the efficacy of the drugs used by sequential combination with sarcosine- or prolinedithiocarbamate seems to be influenced predominantly by diminishing the toxicity as well as by modulating the chemotherapeutic action.

Animals↗
PubMed1994

Phase-II trial with M-CAVe-CEC as a salvage chemotherapeutic regimen for early relapsed or primary refractory Hodgkin's disease.

A substantial number of patients with Hodgkin's disease (HD) do not respond adequately to standard therapy. Patients who relapse later than 1 year after completion of treatment have a good chance of achieving a second complete remission (CR). The prognosis of patients with primary refractory HD or relapse within 1 year, however, is poor. The long-term results of autologous bone marrow transplantation (ABMT) in these patients have not yet been established. Therefore, we conducted a phase-II study among 15 patients with primary refractory or early relapsed HD, in which they were treated with a two-drug sequential regimen not cross-resistant with MOPP. The patients received two to six courses of methotrexate, cyclophosphamide, adriamycin, vinblastine, CCNU, etoposide, and chlorambucil (M-CAVe-CEC). Seven patients (47%) achieved a CR, including a patient with additional radiotherapy. Actuarial overall survival was 58 and 41%, respectively, and failure-free survival 38% at 2 and 5 years. Gastrointestinal toxicity was acceptable. Dose reductions were necessary in up to 60% of courses given. These preliminary results suggest that the M-CAVe-CEC regimen may be a more effective salvage regimen as compared with other regimens for primary refractory or early relapsed HD. Larger studies, possibly with hematopoietic growth factors, are required to determine its value in comparison to ABMT.

Adolescent↗
PubMed1978

Multidisciplinary treatment for central nervous system tumours with nitrosourea compounds.

The authors report the results of a controlled clinical trial in patients with primitive and metastatic CNS tumours treated with combined therapy: surgery, radiotherapy, and chemotherapy (BCNU or CCNU). A total of 102 patients were treated, 50 with BCNU, and 52 with CCNU. The overall response (R. + P.R.) was 68% for the BCNU group, and 65% for the CCNU group. No significant differences were found between the two types of treatment, either in terms of response or in terms of quality and length of survival.

Adolescent↗
PubMedDate not supplied

Adjuvant therapy for adenocarcinoma of the rectum.

Surgical resection continues to be the primary curative modality for patients with adenocarcinoma of the rectum. However, local tumor recurrence in the pelvis and/or distant metastasis may occur in spite of complete excision of grossly visible malignant disease. Surgical and pathologic staging can identify a subset of surgically treated rectal cancer patients at high risk for tumor relapse and death. Irradiation and chemotherapy have been used as adjuvant therapy in conjunction with surgery as single modalities and in combination for patients with high risk rectal cancer. Evidence from controlled clinical trials indicates a significant decrease in local tumor recurrence, and a significant improvement in disease-free and overall survival with the use of combined postoperative irradiation and chemotherapy in this setting. A current national clinical trial in the United States of America is studying whether irradiation can be combined with new chemotherapy regimens which have shown significant therapeutic benefit as surgical adjuvant therapy for patients with high risk colon cancer (5FU + levamisole) and for patients with metastatic colorectal cancer (5FU + leucovorin) to further improve the efficacy of surgical adjuvant therapy for adenocarcinoma of the rectum.

Adenocarcinoma↗
PubMed1986

Dibromodulcitol-based combined postoperative chemotherapy of malignant astrocytomas and glioblastomas.

Continuing our earlier studies with dibromodulcitol (DBD), in a series of 38 evaluable consecutive patients who were operated on for malignant supratentorial gliomas, radiotherapy with smaller daily but higher total doses of DBD has been started 3-5 weeks after surgery. This was followed alternately by a combination chemotherapy of CCNU and DBD or CCNU and Procarbazine. No severe myelotoxicity occurred. Survivals were compared with a group of patients who got irradiation alone. Statistical analysis showed a significantly better survival in the presently treated group: median survival was 55 weeks, p = 0.02. These values were very similar to those groups which were treated by intermittent DBD schedule during irradiation. This study seems to confirm our previous suggestion that the concurrent use of DBD during irradiation might be an important factor in improving survival times.

Adult↗
PubMed1990

The VM model of glioma: preparation of multicellular tumour spheroids (MTS) and their response to chemotherapy.

A cell line, 497-P(1), derived from the VM spontaneous murine astrocytoma has been used to develop an in vitro therapeutic model of human glioma. In this study we describe the preparation of MTS from this cell line. The in vitro chemosensitivity of 497-P(1) MTS has been examined and compared to the sensitivity of the monolayer culture. BCNU and CCNU both produced growth delay in MTS at doses below the ID50 of the monolayer culture. MTS, however, were considerably more resistant to vincristine and procarbazine when compared to the monolayer culture.

Animals↗
PubMed1990

An effective oral combination in advanced relapsed Hodgkin's disease prednisolone, etoposide, chlorambucil and CCNU.

Many patients with advanced Hodgkin's disease continue to need palliative therapy, but where there is no curative intent, patients and doctors may prefer oral treatment only. This paper describes the preliminary experience of such a schedule. A total of 15 patients with advanced relapsed Hodgkin's disease were treated with an oral regimen, PECC (prednisolone at 40 mg daily for 7 days, etoposide at 200 mg/m2 on days 1-3, chlorambucil at 20 mg/m2 on days 1-4 and CCNU at 100 mg/m2 on day 1 only), repeated every 4-6 weeks. 12 patients had been extensively pretreated. 11 patients had extranodal disease and 8 had B symptoms when treatment was started. Eight patients achieved a complete remission, with a median duration of 7+ months, and five achieved a partial remission; the overall response rate was 86%. Haematological toxicity was the major side effect. There were no treatment-related deaths. All patients tolerated treatment well and the oral route has particular advantages for those unwilling or unable to accept intravenous treatment.

Administration, Oral↗
PubMed2003

Survival improvement in patients with glioblastoma multiforme during the last 20 years in a single tertiary-care center.

METHODOLOGY: The survival of 357 consecutive patients with newly diagnosed glioblastoma multiforme (GBM) in three treatment groups reflecting different time-periods of diagnosis (A: 1982-1984; B: 1994/1995; C: 1996-1998) was analysed to assess the impact and the potential improvement of changing treatment strategies in our tertiary-care center. PATIENTS AND METHODS: Group A (n = 100) included all consecutive patients diagnosed from 1982 to 1984 and served as the historical control. Group B (n = 93) included all consecutive patients diagnosed in 1994/1995 and group C (n = 164) those diagnosed from 1996 to 1998. Survival in the three treatment groups (A vs. B vs. C) was analysed according to treatment given after neurosurgical intervention (i.e. no specific therapy versus radiotherapy versus combined radio-/chemotherapy), and according to first-line chemotherapy, age (< 40, 40-60, > 60), sex, and tumor location (hemispheric versus bilateral or multifocal tumors, and tumors involving eloquent brain areas). Survival was analysed using Kaplan-Meier's non-parametric method. A p-value < 0.05 was considered statistically significant. RESULTS: Patients in groups A and B received radio- and/or chemotherapy to a varying extent (radiotherapy: group A: 22%, group B: 62%; chemotherapy: group A: 6%, group B: 33%). Chemotherapy was administered after termination of radiotherapy in both groups. In group C, 96% of patients received combined radio-/chemotherapy which was administered concomitantly and started within three weeks after surgery. Median survival was 5.2 months in group A, 5.1 months in group B and 14.5 months in C (p < 0.0001). Nine patients in group A (9%), 9 in group B (10%) and 40 in group C (25%) survived more than 18 months (p < 0.05). CONCLUSIONS: Survival improvement in group C might be attributable to the early start of combined radio-/chemotherapy. Therapy was administered on a complete outpatient basis, enabled by a dedicated interdisciplinary neuro-oncologic team caring for group C. Toxicity was mild and patients' acceptance excellent.

Adolescent↗
PubMed2003

Monitoring individual response to brain-tumour chemotherapy: proton MR spectroscopy in a patient with recurrent glioma after stereotactic radiotherapy.

Since antineoplastic activity varies, sensitive methods for individual assessment of efficacy are needed. We demonstrate the clinical value of MR spectroscopy in monitoring chemotherapy in a patient with recurrent glioma after stereotactic radiotherapy. Diagnostic imaging before and after chemotherapy included contrast-enhanced MRI, single-voxel proton MR spectroscopy ((1)H MRS), (1)H MR spectroscopic imaging ((1)H SI), and fluorodeoxyglucose (FDG) positron-emission tomography (PET). A significant decrease in choline signal intensity was observed 2 months after chemotherapy indicating tumour chemosensitivity, in line with tumour shrinkage on MRI and decreased uptake of FDG. Assessment of early response by MRS may help to improve treatment protocols in other patients.

Adult↗
PubMed2001

Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma.

PURPOSE: To evaluate the impact of an additive therapy with an oral enzyme (OE) preparation given for more than 6 months additionally to standard combination chemotherapy (vincristine/melphalan/cyclophosphamide/prednisone (VMCP)- or methylprednisolone/ vincristine/CCNU/cyclophosphamide/melphalan (MOCCA)-regimen) in the primary treatment of patients with multiple myeloma stages I-III. METHODS: A cohort of 265 patients with multiple myeloma stages I-III was consecutively treated at our institution in two parallel groups (control group (n = 99): chemotherapy +/-OE for less than 6 months; OE-group (n = 166): chemotherapy + OE for more than 6 months). The median follow-up time in the stages I, II, and III for the OE-group was 61, 37, and 46.5 months, respectively; for the control group the respective values were 33, 51.5, and 31.5 months. The primary endpoint of the study was disease-specific survival. Secondary endpoints were response to therapy, duration of first response and side effects. The chosen method for evaluation was the technique of a retrolective cohort analysis with a concurrent control group. Survival analysis was performed by the Kaplan-Meier method and multivariate analysis was done with the Cox proportional hazards model. RESULTS: Significantly higher overall response rates and longer duration of remissions were observed in the OE-group. Primary responders showed a longer mean survival time than non-responders. Additive therapy with OE given for more than 6 months decreased the hazard of death for patients at all stages of disease by approximately 60%. Observation time was not long enough to estimate the median survival for patients at stages I and II; for stage III patients it was 47 months in the control group versus 83 months for the patients treated with OE (P = 0.0014) which means a 3-year gain of survival time. Significant prognostic factors for survival, in the Cox regression analysis, were stage of disease and therapy with OE. The OE-therapy was generally well tolerated (3.6% of patients with mild to moderate gastrointestinal symptoms). CONCLUSION: OEs represent a promising new additive therapy in multiple myeloma which will be further evaluated in a randomized phase III trial in the USA.

Administration, Oral↗
PubMed2006

Astrocytic tumors in children: treatment results from a single institution.

OBJECTIVE: The aims of this study are to evaluate the patients with astrocytomas and to investigate survival rates and prognosis. PATIENTS AND METHODS: Five hundred fourteen patients diagnosed with brain tumor between 1972 and 2003 were retrospectively analyzed. Three different chemotherapy regimens were used according to years. CCNU-based protocols were used in the early years; COPP (cyclophosphamide, oncovin, procarbazine, prednisolone) and CDDP+VP16 (cisplatinum + etoposide) were the other protocols used in the following years. Radiotherapy was used after 3 years of age according to protocols. RESULTS: Ninety-eight (19%) out of 514 patients have astrocytic histopathology. The histopathologic distribution was as follows: low grade, 55 patients; high grade, 43 patients. COPP regimen was given to 24 patients, CCNU-based regimen to 13, and CDDP+VP16 to 10 patients. We did not use any chemotherapy in 51 patients. Overall survival (OS) and event free-survival rates were 59.2 and 45.7% in whole group. OS rates were 93.3 and 22.4% for low-grade and high-grade histopathology, respectively (p=0.0001). OS for CCNU, CDDP+VP16, and COPP were 35.9, 22.8, and 30.4%, respectively. CONCLUSION: Low-grade astrocytomas are highly responsive to the surgery, and they do not need any further treatment unless the patient has relapse or recurrence. Still, the treatment of the high-grade tumors is a problem, and it needs new treatment approaches.

Adolescent↗