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At least 613 records · Page 34Linked to original sources
PubMed1982

Diamminodichloroplatinum combination chemotherapy in non-oat cell carcinoma of the lung.

A comparison is made between four different but similar approaches to the chemotherapy of 250 patients with nonoat cell bronchogenic carcinoma of the lung. Combination chemotherapy, particularly in regimen where platinum is included, provided no significant advantages over single agent chemotherapy. Side effects attributed to platinum tend to distract from any modest therapeutic gains achieved through its use. Responses rates were not significantly increased through use of platinum in the chemotherapy combination reported in this study.

Carcinoma, Bronchogenic↗
PubMed1982

A critical review of immunotherapy of disseminated renal adenocarcinoma.

Sixty patients with renal adenocarcinoma have been treated with five different immunotherapy trials consisting of 1) Transfer Factor (TF), 2) TF and Bacillus Calmette-Guerin (BCG), 3) TF, BCG, Chloroethyl-cyclohexy-nitrosurea (CCNU) and megestrol acetate (Megase), 4) BCG, CCNU, and Megase, or 5) BCG. Using strict response criteria for measurable disease, objective responses were seen in 14-22% of cases. While this nonspecific immunotherapy of renal adenocarcinoma has been associated with documented regression of metastases, response rates are similar to that obtained with hormonal therapy alone. Objective responses support the concept of further trials in this disease with more sophisticated immunotherapy.

Adenocarcinoma↗
PubMed1983

Adriamycin, CCNU, and 5-fluorouracil in patients with advanced gastrointestinal cancer.

Forty-one patients with measurable advanced gastrointestinal malignancy were treated with a combination of Adriamycin (doxorubicin), 5-FU (5-fluorouracil), and CCNU (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea). The response to therapy was evaluated every eight weeks. In addition to standard clinical examinations and laboratory tests to evaluate toxicity, 31 patients were asked to rank both the expected and experienced negative effects of the treatment. Although both patients with hepatocellular cancer and the patient with a soft tissue sarcoma responded to the regimen, only 1 of 38 patients with adenocarcinoma had a favourable response. The clinically measurable toxicity, principally to the gastrointestinal tract and bone marrow, was relatively mild. However, the patients' subjective evaluation of their treatment made the side effects appear more significant. The results suggest that this regimen deserves further evaluation in patients with hepatocellular cancer and soft tissue sarcomas.

Adenocarcinoma↗
PubMed1983

Comparison of chemotherapy alone versus chemotherapy and radiation therapy of extensive small cell carcinoma of the lung.

In a randomized study 145 patients with extensive small cell carcinoma of the lung were treated with chemotherapy alone (Cytoxan, CCNU, methotrexate) or with the same drug regimen and with radiation therapy to the brain, chest, and abdomen. One hundred eighteen of these patients were evaluable. Those patients receiving radiation had a better response rate (55% vs 31%, P = .016) but significantly greater toxicity. There was no significant difference in rates of complete response (7% vs 8%) or in survival (median 18.4 vs 15.3 weeks) between the two groups overall. The median survival of those patients with a partial response to therapy was 18 weeks; for those achieving a complete response it was 46 weeks. However, a clear difference in survival comparing responders with non-responders was evident only for patients who were assigned to chemotherapy alone. Partial regressions have little, if any, correlation with improvement in survival. Therapy in this disease must be oriented toward inducing complete response.

Aged↗
PubMed1989

Adjuvant chemoimmuno- and immunotherapy in Dukes' stage B2 and C colorectal carcinoma: a 7-year follow-up analysis.

A prospectively randomised controlled clinical trial of adjuvant therapy was undertaken, at a single-centre, population-based cancer institute, in patients with Dukes' stages B2 and C colorectal carcinoma after curative surgery. Between 1976 and 1983, 253 patients were randomised to either control (no further therapy after surgery), immunotherapy (oral bacille Calmette-Guérin [BCG] 120 mg once a month) for 5 years or chemoimmunotherapy (oral BCG as above with methyl-cyclohexyl-chloroethyl nitrosourea [meCCNU] 130 mg/m2 on day 1 and 5-fluorouracil [5-FU] 325 mg/m2/day on days 1-5 and 375 mg/m2/day on days 36-40) repeated every 10 weeks for 8 cycles. The median follow-up of patients is now 6.95 years. Of the control, immunotherapy, and chemoimmunotherapy groups 22.35%, 39.28%, and 28.57%, respectively, have relapsed. The log-rank analysis of results shows no disease-free or overall survival advantage for patients receiving adjuvant therapy compared with the control group. Patients receiving adjuvant immunotherapy for stage B2 appear to have a significantly inferior disease-free survival compared with other groups, but their overall survival is similar. There are no significant differences in disease-free or overall survival in the three groups of patients with stage C tumour. Of 82 patients dying, 78.05% died of progressive colorectal carcinoma, 13 patients developed a second malignancy; the remainder died of seemingly unrelated causes.

Adenocarcinoma↗
PubMed1995

Neoadjuvant chemotherapy of stage III-A and B lung carcinoma using the PACCO regimen.

Previously, we reported an effective chemotherapeutic combination regimen for non-small cell lung carcinoma (NSCLC): cisplatinum, doxorubicin, cyclophosphamide, CCNU, and vincristine (PACCO). Forty-one patients with a diagnosis of NSCLC Stages III-A and III-B were entered into the protocol of neoadjuvant PACCO chemotherapy. Following two courses of chemotherapy, the patients were evaluated for surgical therapy. The overall response rate to the chemotherapy was 60%. Subsequently, 65% of the patients underwent surgical resection. The overall estimated median survival was 18 months. The survival of patients in III-A was 36 months and that of III-B was 18 months (95% confidence lower bounds for III-A: 8 months and for III-B: 13 months). There was one chemotherapy-related mortality but no surgical mortality. Neoadjuvant chemotherapy with PACCO regiment offers an alternative to chemoradiation therapy, without increasing the surgical mortality, and should be validated in a randomized clinical trial. For successful neoadjuvant chemotherapy of Stage III NSCLC, chemotherapy combination which would give a high response rate without significant side effects must be chosen.

Adult↗
PubMed1995

Mutational specificity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in the Escherichia coli lacl gene of O6-alkylguanine-DNA alkyltransferase-proficient and -deficient strains.

Forward mutations induced by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in the lacl gene of Escherichia coli were recovered from bacteria proficient (Ogt+ Ada+) and deficient (Ogt- Ada-) in O6-alkylguanine-DNA alkyltransferase activity. A CCNU dose of 1 mM was selected for DNA sequence analysis. A total of 245 induced mutations were characterized. The mutations were almost exclusively (95%) GC-->AT transitions, indicating that CCNU-induced mutations arose in bacteria primarily from misreplication of O6-chloroethylguanine, in total agreement with results obtained for monofunctional alkylating agents. The distribution of CCNU-induced GC-->AT mutations was significantly altered by the presence of DNA alkyltransferase activity (P = 0.01). In the Ogt+ Ada+ mutational spectrum, guanines flanked on both sides by A:T base-pairs were on average 2.8 times more likely to mutate than those flanked by G:C base-pairs on at least one side. This bias disappeared in the Ogt- Ada- genetic background, thereby providing evidence that O6-chloroethylated guanines adjacent to G:C base-pairs are better targets for bacterial alkyltransferase than those not adjacent to G:C base-pairs. We recently reported a similar bias for ethyl methanesulfonate, strengthening the idea that CCNU is acting as a simple ethylating compound. In summary, this paper presents for the first time evidence that DNA repair by O6-alkylguanine-DNA alkyltransferases plays a major role in removing lesions responsible for GC-->AT transitions induced by CCNU, influencing their ultimate distribution with respect to sequence context.

Antineoplastic Agents↗
PubMed1975

Response of 65 measurable epidermoid bronchogenic tumors of known spontaneous doubling time to four different chemotherapeutic regimens--strategic deductions.

Variations in the dimensions of 65 bronchogenic epidermoid tumors of known spontaneous doubling time were studied under the influence of four chemotherapeutic regimens: cyclophosphamide, 19 cases; Mitomycin C, 20 cases; CCNU, 9 cases; and a five-drug combination, 17 cases. Several parameters were measured, and escape was defined as the moment in time when the growth curve during treatment became parallel to the spontaneous growth curve. The parameters measured were nature and distribution of responses (unchanged progression, slowing-down, plateau, regression), duration of response, time required to achieve maximum response, and time lapse between maximum response and escape. Regarding application to lung cancer, we have concluded from out results that Mitomycin C should replace cyclophosphamide in combination chemotherapeutic regimens. With regard to general strategy, our results suggest that the drug regimen should be changed as soon as maximum response is reached or immediately following the first course if progression continues unchanged. Moreover, in all of the 27 patients whose tumors regressed, escape occurred within less than three months from the onset of the treatment. In view of this fact and insofar as chemotherapy is considered for adjuvant therapy aiming at complete eradication, sequential combinations would be preferable to prolonged administration of a single agent or combination.

Carcinoma, Bronchogenic↗
PubMed1975

CCNU and bleomycin in the treatment of cancer: a Southwest Oncology Group Study.

CCNU and Bleomycin, alone or in combination, were used to treat 397 evaluable cases of advanced cancer. Responses defined as 50% or greater reduction in all tumor masses occurred in 13/35 lymphomas, 8/50 brain cancers, and 28/312 other solid tumors. Hematologic toxicity of a life-threatening degree occurred in 33/298 patients evaluable for CCNU toxicity; in an additional 50 it was considered severe. Pulmonary toxicity was severe in 4 patients. Drug-associated deaths (4) included one each due to leukopenia and thrombocytopenia after CCNU; one due to pulmonary toxicity after Bleomycin; and one due to shock after the 20th dose of Bleomycin. There was no suggestion of synergism or additive activity with the two drugs.

Adenocarcinoma↗
PubMed1977

Combination chemotherapy of advanced previously treated Hodgkin's disease with streptozotocin, CCNU, adriamycin and bleomycin.

Seventeen patients with advanced, previously treated Hodgkin's disease received therapy with a combination of streptozotocin 500 mg/m2/day i.v. days 1--5, CCNU 100 mg/m2 orally day 1, adriamycin 45 mg/m2 i.v. day 1, and bleomycin 15 mg/m2 i.m. days 1 and 8 at 28-day intervals (SCAB). The overall response rate was 59% with six patients (35%) achieving complete remission and four patients (24%) entering partial remissions. No maintenance therapy was given and the median duration of complete remission was 8+ months (range 2+-18+ months), while the median duration of partial remission was only 2 months (range 2-3 months). The median duration of survival from the start of therapy for the complete responders was 16+ months (range 5+-25+ months) while the median survival for the partial and nonresponders was only 5 months (range 2-13 and 3-11+ months, respectively). Toxicity was a major problem with this drug combination. Myelosuppression occurred regularly and was severe after 25% of courses. There were two deaths directly related to drug-induced myelosuppression. Other serious toxicities included bleomycin-induced pulmonary toxicity in three patients, with one death; renal tubular dysfunction secondary to streptozotocin in three patients; hepatic dysfunction in three patients and severe weight loss in three. SCAB has proven to be an active although toxic combination which is not cross-resistant to MOPP-type regimens. Alterations in drug dosages and scheduling are being evaluated in an effect to ameliorate toxicity and preserve efficacy.

Adolescent↗
PubMed1978

Central nervous system tumors of childhood treated with CCNU, vincristine, and radiation.

CCNU was used in the treatment of 18 patients with childhood tumors of the CNS. Severe bone-marrow toxicity was noted. The initial dose was 130 mg/m2 given every 6 weeks, but it was often necessary to reduce the dose and prolong the interval between doses. The toxicity appeared to be much the same whether previous radiotherapy had been given to the whole CNS or to the brain only. In assessable patients with pur medulloblastoma, three out of three showed marked responses to CCNU. In those with a mixture of medulloblastoma and other tumor components, two out of two showed responses to CCNU. In children with astrocytomata of various types, only two out of six showed responses to CCNU, and in these the degree of response was slight. The results suggest that CCNU is a useful treatment for medulloblastoma but its value in the treatment of childhood astrocytoma is uncertain. In 6 patients who received both radiotherapy and CCNU, the contribution of the CCNU was not assessable.

Adolescent↗
PubMed1978

Treatment of oat-cell carcinoma of the lung in the community.

Nine patients with "limited" (thoracic) small-cell lung carcinoma were treated with combined chemotherapy and radiotherapy (involved field and prophylactic whole brain). Induction drugs were Vincristine, Adriamycin, and Cyclophosphamide; and Cyclophosphamide, Vincristine, and CCNU for maintenance. Eight out of nine patients (89%) continue NED at a median follow-up time of 12 months. This group is compared to 21 patients with more extensive disease and 6 patients with limited disease using various other regimens. Median survival in the extensive group was 5 months and 8 months for the limited-diseased group treated with single agents. Intensive combination chemo-irradiation therapy is safe and highly effective in patients with limited oat-cell carcinoma of the lung, and leads to prolonged disease-free survival.

Antineoplastic Agents↗
PubMed1978

CCNU, vinblastine, and delalutin therapy in renal cell carcinoma.

Advanced renal cell carcinoma is relatively resistant to most adequately evaluated chemotherapeutic agents. The combination of CCNU and vinblastine, which has antitumor activity in a frog renal carcinoma model system, has demonstrated activity in initial studies in man. The current study investigated this combination of drugs together with a progestational agent, Delalutin. Seventeen patients with metastatic renal cell carcinoma were treated with CCNU, vinblastine and Delalutin. There were no objective responses. Four patients with stable disease had a mean survival of 18 months compared to 13 patients with progressive disease who had a mean survival of 5 months. The survival of the four patients with stable disease was in large part due to the slowly progressive natural history of their disease.

Adenocarcinoma↗
PubMed1984

Evaluation of cyclocytidine in reinduction and maintenance therapy of children with acute nonlymphocytic leukemia previously treated with cytosine arabinoside: a report from Children's Cancer Study Group.

A study of children in relapse with acute nonlymphocytic leukemia (ANLL) previously maintained in remission with combination chemotherapy including cytosine arabinoside (Ara-C) was undertaken by Children's Cancer Study Group (CCSG) to assess the efficacy of cyclocytidine (Cyclo-C), a depot Ara-C, compared to parenteral Ara-C given every 12 hr. The reinduction protocol consisted of daunomycin combined with either Ara-C (Regimen 1) or Cyclo-C (Regimen 2). One-hundred thirty eligible patients were entered on the randomized study. Hematologic toxicity was significant in both regimens and resulted in four drug-related deaths. Cardiac toxicity was observed in five patients, manifested only by abnormal echocardiogram or electrocardiogram patterns in three and congestive heart failure in two patients. Seventy-seven of 112 evaluable patients achieved M-1 or M-2A marrow remissions (69%): 46 of 60 on Regimen 1 (75%), 30 of 52 on Regimen 2 (60%). The remission rate between the two regimens was not significantly different. There was no significant difference in the duration of remission comparing maintenance cyclophosphamide combined with Ara-C or with Cyclo-C. Addition of VP-16 and CCNU to the maintenance therapy did not prolong the duration of remission. This study indicates that patients with childhood ANLL previously treated with Ara-C and daunomycin can obtain a successful second remission. A single daily subcutaneous dose of Cyclo-C was found to be as efficacious as Ara-C given intravenously every 12 hr. The single dose schedule provides a convenient way to treat patients with relapsed ANLL in the outpatient setting.

Adolescent↗
PubMed1993

Carcinoma of the choroid plexus: a pediatric experience.

Carcinoma of the choroid plexus (CCP) is a rare tumor of the central nervous system which occurs more frequently in patients under 3 years of age. We report 10 cases of CCP in children. There were 5 males and 5 females, aged 5 to 84 months at diagnosis (median 32 months). Eight CCP were located in the lateral ventricle and 2 in the fourth ventricle. All patients underwent initial surgery, with complete resection in 5 cases. Postoperative treatment included radiotherapy alone in 4 patients, chemotherapy alone in 4, both in 1 patient, and no further treatment in one patient. Six patients remain in first continuous complete remission with a follow-up of 12 to 156 months (mean 34 months). Five of these six patients had a complete surgical resection of their tumor and 4 of them received chemotherapy alone. A comparison with the series in the literature suggests that total resection of the tumors is the major prognostic factor for survival. Recourse to additional treatments to prevent local relapses and CNS dissemination seems necessary. In our opinion, radiotherapy should be avoided as far as possible because of its deleterious effect in very young children. As some of the long term survivors did not receive radiation treatment, we conclude that CCP can be treated post operatively using chemotherapy protocols designed for infants with malignant brain tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Pediatric Hodgkin's disease in Costa Rica: twelve years' experience of primary treatment by chemotherapy alone, without staging laparotomy.

This is a prospective and nonrandomized study in which 86 children with previously untreated Hodgkin's disease (HD) were clinically staged (CS) and treated with chemotherapy (CT) alone. Fifty-two (CS IA-38, IIA-7, IIB-3, IIIA-4) received six courses of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP). Ten (CS IA with peripheral nodes) received only three courses of CVPP with a reinforcement of C on day 8. Twenty-four (CS IIIB-18, IVA-2, IVB-4) received six courses of CVPP alternating with six courses of epirubicin, bleomycin, and vincristine (EBO). Surgical staging was not performed in any patient. Two patients (CS IIIB) had partial remission and died from progressive disease. Seventy out of 86 children have not relapsed and are in complete remission with a median follow-up of 65 months (range 13-156 months); 14 children relapsed seven to 37 months from diagnosis (median 16 months); one of them (IV B) died of disease. Thirteen are in second and third remission (median 55 months). Actuarial five year survival rates and relapse-free survival rates are 100% and 90% for CS I to IIIA and 81% and 60% for CS IIIB and IV, respectively. As a result of this study, we can conclude that in developing countries most of the children with HD staged by noninvasive diagnostic techniques can be cured with CT alone as primary treatment and thus will not suffer from the late effects of radiotherapy (RT) and the morbidity of laparotomy and splenectomy. RT alone or with other CT combinations should be considered for children who develop relapse of HD.

Adolescent↗