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PubMed1986

No response improvement after sequential chemotherapy for small cell lung cancer.

In a phase II study in patients with small cell lung cancer (SCLC) the combination of cyclophosphamide, cisplatinum and etoposide was found to be active, the response rate was 91% (30% CR, 61% PR) in the whole group. In 40 limited disease patients 19 CR (48%) and 20 PR (50%) were seen, whereas in 30 extensive disease patients only 2 CR (7%) and 23 PR (77%) were reached. Adding a second combination of doxorubicin, vincristine and procarbazine resulted in response improvement in only two patients. Median response duration was 41 weeks in CR patients and 30 in PR patients (p less than 0.01). Median survival was 66 in CR and 45 weeks in PR patients (p less than 0.002). Performance score and disease stage were found to be good prognostic factors. Four patients (6%) are disease-free at 2 1/2 years. The value of sequential chemotherapy for SCLC is probably minimal in view of the lack of response improvement.

Adult↗
PubMed1986

[Assessment of the quality of life of cancer patients. The preliminary applications to advanced bronchial cancers].

So far there is no good evidence that chemotherapy improves survival in non small cell lung cancer. Reports of randomized trials testing chemotherapy versus supportive treatment alone are very few. In recent years, more and more emphasis has been put on the quality of life for cancer patients. Subjective tests such as Anamnestic comparative self Assessment (A.C.S.A. test, Dr. Bernheim) were designed as well as objective ones, using different types of self evaluation. However very few studies have been focused on this aspect in patients with non small cell lung cancer. Therefore the G.E.T.C.B. (Groupe d'Etude et de Traitement des Cancers Bronchiques) decided to initiate a cooperative randomized trial (02 CB 84) in metastatic epidermoid and large cell bronchus carcinoma, in order to test the potential benefit from chemotherapy in these tumors and how it affects the quality of live. In this trial, C.O.P.A.C. combination (Cyclophosphamide, Vincristine, Cis-Platinum, Adriamycin and CCNU) is randomized versus no chemotherapy. The quality of life is assessed monthly on the one hand by a modified A.C.S.A. test performed by a physician and on the other hand by a question list given to the patient. This question list attempts to evaluate the impact of disease as a reference point. Finally protocol 02 CB 84 (activated in 05/84) may give information about the effect of chemotherapy on both survival and quality of life.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Prognostic factors in patients with small-cell carcinoma of the lung.

Fifty-two patients with histologically confirmed small-cell carcinoma of the lung, 15 with disease localized to one hemithorax and 37 with extensive metastases, were studied. Only patients whose general condition was considered good enough to tolerate intensive combination chemotherapy were included in this study. The median survival time of these patients was 33 weeks (range 7-192 weeks) with a mean survival time of 43 weeks. Patients who responded with objective tumour improvement within 6 weeks had a median survival time of 39 weeks. Those showing disease stabilization at 6 weeks had a median survival time of 35 weeks while those having disease progression at this time had a median survival of 22 weeks. Patients without liver involvement and a normal serum albumin level at the start of treatment had statistically superior survival times.

Adult↗
PubMed1986

[CMC chemotherapy regimen combined with surgery of small cell lung cancer (SCLC)].

From Dec. 1982 to Oct. 1984, 35 patients with SCLC proved by pathology or cytology, were treated by cyclophosphamide + methotrexate + CCNU (CMC) regimen combined with surgery in our hospital. All the patients received chemotherapy for more than 2 courses and the overall response rate was 85.7%, complete remission (CR) rate was 14.3%. Toxic reactions were tolerable to the patients. Treatment result was better in SCLC with localized than extensive disease. Operation was done for 9 out of 21 patients with localized lesions which had responded to chemotherapy. Of them, 1 died of postoperative complication, 2 were lost in follow-up and the rest 6 were disease-free for 8-32 months with a median survival time of 19 months. The 1 year survival rate was 75%. The results indicate that in limited disease of SCLC, successful chemotherapy combined with surgery can prolong the survival time. For patients with an limited disease which has given a CR, surgical resection should be strived for.

Adult↗
PubMedDate not supplied

In vitro and in vivo activity of 1-aryl-3-(2-chloroethyl) urea derivatives as new antineoplastic agents.

A few 1-aryl 3-(2-chloroethyl)ureas (CEU) were synthesized and screened in vitro for their cytotoxicity. Some of these derivatives were assayed for their mutagenicity, their in vivo toxicity and their antineoplastic activity. Methyl 4-(p-(3-(2-chloroethyl) ureido) phenyl) butyrate, 4-methyl and 4-tertbutyl (3-(2-chloroethyl) ureido) phenyl) butyrate, 4-methyl and 4-tert-butyl (3-(2-chloroethyl) ureido) benzene had an ID50 of 28, 20 and 4 microM respectively when tested on LoVo cells, while chlorambucil (CBL) and CCNU had an ID50 of 21 and 45 microM. These 3 chloroethyl urea derivatives were not toxic when injected i.p. at doses up to 220 mg/kg, whereas chlorambucil was already toxic at 18.5 mg/kg. The survival time of BDF1 mice bearing L1210 leukemia tumors was significantly enhanced by intraperitoneal injections of CBL and CEU. The most cytotoxic derivative (tert-butyl derivative) gave the best antineoplastic activity with a median survival time 1.77 times that of the control at 10 mg/kg/day and was not toxic, whereas CBL at this concentration enhanced survival time by a factor of 1.6 and presented important side effects. The 4-tert-butyl (3-(2-chloroethyl) ureido) benzene and the methyl 4-(p-(3-(2-chloroethyl) ureido) phenyl) butyrate showed no mutagenicity when assayed on TA-97, TA-98, TA-100 and TA-102, four strains of S. thyphimurium, while CBL had a weak effect on TA-102 and CCNU was highly mutagenic on TA-100 and TA-102.

Adenocarcinoma↗
PubMed1988

Responses of tumor cell subpopulations to single modality and combined modality therapies.

By centrifugal elutriation, viable cell subpopulations were isolated directly from KHT sarcomas treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, mitomycin (MIT C), cyclophosphamide (CTX), or radiation. Survival in these subpopulations was determined by a clonogenic cell survival assay either immediately (radiation) or 24 hours after treatment with drugs. Following irradiation, late S and G2/M cells were found to be sensitive, but G1 cells were preferentially spared. For all chemotherapeutic agents evaluated, survival of cells at the G1/S boundary 24 hours after drug exposure was at a nadir, whereas cells in the late S and G2/M at this time were always drug resistant. The response of cells in early G1 24 hours after drug treatment ranged from sensitive (MIT C) to resistant (CTX). Because of these results, the combination of MIT C and radiation was investigated in detail. When MIT C was administered 24 hours before tumor irradiation, the chemotherapeutic agent significantly reduced the radiation-resistant subpopulations, whereas the radiation treatment effectively killed cells spared by the chemotherapeutic agent. Isobologram analysis further indicated that this treatment combination led to "supra-additive" cell kill in the tumor.

Animals↗
PubMed1988

Modification of calmodulin on Lys-75 by carbamoylating nitrosoureas.

This paper describes characterization of the reaction of calmodulin with a series of nitrosoureas which are capable of releasing amine-reactive isocyanates of varying hydrophobic character. The site of calcium-dependent carbamoylation on calmodulin by the antineoplastic agent 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl CCNU) was determined to be Lys-75 as demonstrated using [ring-14C]methyl CCNU and sequence analysis of the sole labeled peptide obtained from tryptic digestion of reversed-phase high pressure liquid chromatography (HPLC)-purified radiolabeled calmodulin. CCNU, the 4-desmethylcyclohexyl derivative of methyl CCNU, and its reactive hydrolysis product, cyclohexyl isocyanate, were also determined to modify calmodulin in a similar manner and at the same site, as demonstrated by specific blockade of modification by the calmodulin antagonist calmidazolium. Nitrosoureas which release the less hydrophobic 4-hydroxy- and 4-carboxycyclohexyl isocyanates are unable to modify calmodulin at 25-fold higher concentrations than those required for modification with methyl CCNU, CCNU, or cyclohexyl isocyanate. With this monomodified Lys-75 derivative, purified to homogeneity by HPLC, differential effects of modification on the activation of bovine brain 3',5'-cyclic nucleotide phosphodiesterase (phosphodiesterase) and human erythrocyte Ca2+,Mg2+-ATPase were observed. Compared to the amounts of native calmodulin needed, phosphodiesterase required 7-fold higher amounts of this derivative to reach maximal activation, whereas the activation of the ATPase was unaffected. Clearly, different regions of calmodulin are responsible for the activation of phosphodiesterase and the ATPase. We conclude that Lys-75 is not essential for the function of calmodulin but is in a region of the molecule involved in interaction with phosphodiesterase as well as the binding of certain hydrophobic calmodulin antagonists.

Amino Acid Sequence↗
PubMed1985

[New developments in chemotherapy for experimental brain metastasis].

Numerous animal models of brain tumor have been developed for screening new chemotherapeutic agents effective for brain tumors. However, most of these models have problem (s) of mechanical disruption of the blood-brain barrier by tumor inoculation and/or discrepancy in histologic nature and site of growth between inoculated tumors and human tumors. With the purpose of establishing a better model for the evaluation of antitumor activity, we have developed rat models of leptomeningeal tumors by intralateral-ventricle inoculation of myelogenous leukemia cells (DBLA-6) or AH130 ascites hepatoma cells. It was proved that in the two models there was no disruption of blood-brain barrier function by tumor inoculation and that the histologic pattern of DBLA-6 model tumor closely resembled the diffuse meningeal involvement of leukemic cells seen in the human disease. Using these models, several antitumor agents have been tested and ACNU, CCNU and procarbazine were found to be highly effective when given intravenously or intraperitoneally, and the intralateral-ventricle administration of methotrexate was also found to show a moderate antitumor activity. Furthermore it was found that intraperitoneal administration of spirohydantoin mustard, and intralateral-ventricle administration of 5-fluorodeoxyuridine were highly effective against the AH130 model.

Animals↗
PubMed1988

Adults with Ewing's sarcoma. An analysis of 16 patients at the Dana-Farber Cancer Institute.

Between 1975 and 1985, 16 patients with Ewing's sarcoma were treated in the Adult Sarcoma Clinic at the Dana-Farber Cancer Institute. Of 10 patients with extraskeletal or pelvic primaries, 2 (1 pelvic, 1 extraskeletal) are surviving disease-free at 77 and 103 months from diagnosis. Of the six remaining patients, 5 are alive from 38 to 125 months from diagnosis. No relapses were documented after 18 months of disease-free survival. Adults with localized skeletal Ewing's sarcoma outside the pelvis respond well to multimodality therapy. However, pelvic and extraskeletal disease occur in a disproportionately large segment of this older population and are associated with a poor prognosis.

Adolescent↗
PubMedDate not supplied

[Analysis of the results of combined treatment of poorly differentiated brain gliomas].

In a group of 139 patients with poorly differentiated brain gliomas controlled clinical trial was carried out for assessment of two methods of postoperative treatment. After possibly radical removal of the glioma the patients were treated by radiotherapy with 60Co teletherapy in doses of 60 Gy (30 fr) in depth during 6 weeks, and randomly chosen patients received also CCNU in one dose of 100 mg/m repeated at intervals of 6-8 weeks. The administration of CCNU failed to improve the therapeutic results. The median survival time in the whole group was 49 weeks. The survival rate after 1, 2 and 3 years was 45.4%, 22.8% and 14.9% respectively. The survival times of cases of glioblastoma multiforme were not significantly different from those of patients with other poorly differentiated gliomas independently of the treatment method. The complications were not troublesome.

Adolescent↗
PubMedDate not supplied

New drugs of 1976.

Explore the source record for details and available documents.

Acetanilides↗
PubMed1988

An approach to reduce treatment and invasive staging in childhood Hodgkin's disease: the sequence of the German DAL multicenter studies.

UNLABELLED: From June 1978 through March 1987, 506 children under the age of 16, representing approximatively 70% of the children with Hodgkin's disease in West-Germany entered 3 consecutive multicenter studies at 68 centers. The general objective of these study sequence is to maximize the chance of cure while minimizing radiotherapy and chemotherapy as much as possible in a combined modality treatment concept. The purpose was also to reappraise the need for splenectomy and laparotomy and to define a staging policy which provides adequate evaluation of intraabdominal disease. Study II (HD-82) is described in detail. 203 protocol patients were enrolled between Dec. 1981 and Dec. 1984. Laparotomy was performed in 202 patients, but splenectomy only in 78 (38.4%) using an intraoperative decisional strategy, developed in Study I (HD-78). Patients were stratified according to stage into 3 groups (PS I/IIA, IIB/IIIA and IIIB/IV) receiving 2, 4 or 6 cycles of OPPA/COPP-chemotherapy. Radiotherapy was given only to the involved fields, the dose depending on the extent of chemotherapy (35, 30 or 25 Gy). RESULTS AND CONCLUSIONS: The event-free survival rates after 5 years are 96% (entire group), 99% (stage I/IIA), 96% (stage IIB/IIIA) and 90% (stage IIIB/IV). Thus, only involved field radiotherapy with reduced doses is needed, if a stage-dependent chemotherapy with 2, 4 or 6 cycles of OPPA/COPP is given. The strategy of selective splenectomy has proven very useful. Based on statistical analyses concerning abdominal involvement a clinical decisional strategy for selective laparotomy was developed. Further efforts are needed to reach a stepwise cautious and controlled narrowing-in on the therapy combining the lowest long-term toxicity with the highest chance of cure.

Adolescent↗