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PubMed1983

Three-drug chemotherapy combined with radiation therapy in small cell carcinoma of the lung.

In 43 cases of small cell carcinoma of the lung, a combined treatment has been initiated with three drugs (cyclophosphamide 750 mg/m2, adriamycin 50 mg/m2 and vincristine sulphate 1 or 2 mg total dosage), split-course-radiation therapy on the primary tumour (3500 rads) and prophylactic irradiation of the brain (2000 rads). The median survival of the 34 cases evaluable at day 50 attains 253 days. A more favourable evolution is observed for patients with a good response after therapy (median survival: 315 days) and for cases with limited disease (321 days) than for non-responders (median survival: 157 days) and for cases with extensive disease (median survival: 214 days). In spite of tumour site irradiation, prophylactic irradiation of CNS and chemotherapy, there were six local relapses, two CNS extensions and six metastatic relapses and only two autopsied cases without macroscopic evidence of relapse.

Adult↗
PubMed1983

[Parathyrin content of lung cancer patients undergoing surgical and chemotherapeutic treatment].

Parathyrin concentration was determined in lung cancer patients prior to and after operation by using a radiological method. A preoperative elevated level of parathyrin was noted in 60.4% of the patients. Radical surgery resulted in the return of the parathyrin level to normal, and toxic effects caused by chemotherapy were accompanied by its sharp increase. A similar increase in the parathyrin level attends generalization of a tumor process.

Adenocarcinoma↗
PubMed1983

[Antimitotic chemotherapy of supratentorial cerebral glioma in adults. Apropos of 56 cases].

Fifty-six patients with supratentorial gliomas were given chemotherapy (VM 26 and CCNU). Results were analyzed and compared to recent data from the medical literature. After the first great expectations the place of chemotherapy in the management of primary gliomas has now been more accurately delineated: it is an adjunctive therapy, complementary to surgery and radiotherapy. The contribution of chemotherapy, although slight, is unquestionable: in 2/3 of cases a significant improvement of the length of survival can be expected.

Adult↗
PubMed1983

[Irradiation of the brain in the combined treatment of small-cell lung cancer].

A study on the advantages offered by a "prophylactic" cranial irradiation in cases of localized small cell cancer of the lung has been conducted at the Center since April of 1981. The report deals with preliminary results on tolerance and immediate reactions of the brain obtained on the basis of 25 cases. A good tolerance of doses ranging 25-30 Gy was recorded. Acute reactions followed gamma therapy in 32% which, however, did not prevent the completion of the full course of prophylactic irradiation. Neurologic symptoms developed after cranial irradiation in 3 cases; this was interpreted as a possible post-radiation encephalopathy. Metastasis was found in one case. The results suggest that the study be continued.

Adult↗
PubMed1983

[Combined (surgical and drug) therapy of lung cancer].

The paper deals with an evaluation of the immediate and end results as well as the rates of lung tumor progression in the course of surgical and combined therapy including different schedules of long-term administration of preparation CCNU. Combined therapy was shown to be followed by a longer remission and survival, as compared with cancer patients in control. The said effect was particularly pronounced is cases of squamous-cell carcinoma and in patients treated with levomycetin.

Adenocarcinoma↗
PubMed1983

[Adriamycin in the combined chemotherapy of small-cell lung cancer].

The results of combined chemotherapy and chemoradiotherapy of 158 patients with small cell lung cancer are presented. Adriamycin was used as one of the components of the induction chemotherapy of 98 out of the 158 patients. Chemoradiotherapy (nitrosomethylurea, methotrexate, CCNU, adriamycin, vincristine, DTIC, radiotherapy) was performed according to 4 schemes and combined chemotherapy (cyclophosphamide, adriamycin, methotrexate, or CCNU, cyclophosphamide, methotrexate plus adriamycin, vincristine, natulan) was performed according to 2 schemes. The total efficacy (complete and partial regression) of the 6 schemes averaged to 80 per cent. The number of patients with complete regression amounted to 29 per cent. Long-term survival for more than 2 years was observed in 17 per cent of the patients. No signs of metastases or relapses for 5 years were recorded in 6 per cent of patients. Adriamycin is one of the most active antitumor drugs in combined chemotherapy and chemoradiotherapy of small cell lung cancer.

Carcinoma, Small Cell↗
PubMed1983

Continuous versus alternating combination chemotherapy for advanced small cell carcinoma of the lung.

In a 2-year period, 146 patients with small cell carcinoma of the lung, staged as having extensive disease, were randomized to receive either continuous chemotherapy consisting of (a) 1-(2-chloroethyl-3-cyclohexyl-1-nitrosourea, cyclophosphamide, methotrexate, and vincristine followed by (b) 4'-demethylepipodophyllotoxin 9-[4,6-O-(R) ethylidene-beta-D-glucopyranoside] and doxorubicin at progression of disease or a regimen of (a) alternating with (b). Seventy-six patients received the continuous regimen; 70 patients received alternating treatment. Response rates were 68 and 72%, respectively. The median duration of response was 16 weeks in patients receiving continuous treatment compared to 28 weeks in patients receiving alternating treatment (p less than 0.05). No survival time difference was observed between the groups, median survival being 36 and 38 weeks, respectively. Four patients became long-term survivors (5.6 +, 5.5 +, 5.1, and 4.7 + years). All received alternating therapy. Six toxic deaths were observed among patients receiving continuous therapy compared to only one death among those in the alternating regimen. In conclusion, alternating combination chemotherapy leads to prolonged duration of remission. Duration of survival is not prolonged in uncured patients, but an increased possibility of long-term disease-free survival cannot be precluded.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

[Triple biphasic chemotherapy in the treatment of small-cell bronchial cancer].

Forty-three patients with small-cell bronchial carcinoma were treated with sequential combination chemotherapy of the CMC-VAP type alternating every 6 weeks. Toxicity affected mostly blood cells and occurred during induction. The response rate was 60% in circumscribed forms with a median survival of 15 months, and 30% in diffuse forms with a median survival of 6 months. The value of alternating protocols and the place of radiotherapy are discussed in the light of these results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Cellular and molecular mechanisms of the bone marrow sparing effects of the glucose chloroethylnitrosourea chlorozotocin.

1,(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and other chloroethylnitrosourea anticancer agents in clinical use produce severe and cumulative bone marrow toxicity. Chlorozotocin, a glucose analogue, has demonstrated reduced hematologic toxicity while retaining full antitumor activity. The biochemical-pharmacologic properties of chlorozotocin and CCNU were compared in human bone marrow. After a 2-hr incubation with a 0.1-mM drug concentration, total cellular uptake of chlorozotocin in whole marrow was 2.47 +/- 0.80 pmole/10(4) cells and was not significantly different compared to the uptake of 1.94 +/- 0.53 pmole/10(4) cells with CCNU. The quantitative alkylation of bone marrow DNA by chlorozotocin, 22.8 +/- 1.2 pmole/mg DNA, was equivalent to that produced by CCNU, 22.9 +/- 0.5 pmole/mg DNA. Bone marrow was separated into 14 fractions by centrifugal elutriation. CCNU uptake was found to be greater than that of chlorozotocin in 3 fractions that were primarily composed of lymphocytes, monocytes, and normoblasts. Chlorozotocin uptake was greater than CCNU in 6 fractions that contained primarily mature and immature myeloid cells as well as the highest CFU-GM activity. The two drugs produced a comparable degree of DNA strand breakage and DNA-protein cross-linking as measured by alkaline elution of pooled fractions of elutriated bone marrow. DNA interstrand crosslinking was not found with either drug. The most significant finding of this study is the differences in the site of drug alkylation by chlorozotocin and CCNU in bone marrow chromatin. Endonuclease digestions with MCN, DNase I, and DNase II showed nonrandom alkylation of specific regions of chromatin by the two drugs: CCNU demonstrated a preferential binding to the transcriptionally active regions of chromatin, whereas chlorozotocin predominantly alkylated the transcriptionally inactive regions. These data suggest that the lethal damage of nitrosourea alkylation in human bone marrow is principally expressed in transcriptionally active regions of chromatin.

Antineoplastic Agents↗
PubMed1984

Changes in T and B lymphocyte subpopulations before, during and after chemotherapy for malignant melanoma.

The behaviour of T and B lymphocyte subpopulations before, during and after chemotherapy with DTIC or CCNU was studied in 87 melanoma patients. The effect on immune status of DTIC administered as adjuvant therapy was also reported. The immunosuppressive effect was found to be higher in patients with normal pretreatment T-cell values than in patients with low pretreatment values, and it was higher in metastatic than in nonmetastatic patients. Where T and B lymphocyte subpopulations were assessed in 10 metastatic patients after each course of chemotherapy, a progressive reduction of T-lymphocytes was observed, indicating a cumulative effect of the drugs with advancing course. The reduction of T lymphocytes was mainly due to the decrease of OKT4+ cells. A normalization of T lymphocyte subpopulations was observed after the suspension of therapy. No significant decrease in the number of B cells was observed in the DTIC treated metastatic patients, whereas a significative reduction in the absolute number was found in those treated with CCNU.

Aged↗
PubMed1983

Combination chemotherapy in metastatic or recurrent non-small cell bronchogenic carcinoma. 5-year results.

A controlled clinical trial was performed to test two different chemotherapy regimens (doxorubicin + cyclophosphamide + vincristine versus CCNU + vincristine) in 100 patients with metastatic or recurrent non-small cell bronchogenic carcinoma. There was no significant difference between treatment groups in survival or in response. Only 4 patients had a partial remission and there were no complete responders. Median survival was 7 months and 8 patients lived over two years, one patient is still alive (65 + months). The benefit of combined chemotherapy in non-small cell bronchogenic carcinoma remains minimal.

Adult↗
PubMed1984

Thymic hormonal effect on recovery from early and late CCNU induced immunosuppression.

The alkylating agent 1(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) caused a prolonged suppression of antibody response to sheep red blood cell challenge in mice. Two phases of suppression could be observed, an early (first three weeks after CCNU administration) and late phase (4-10 weeks). The late immunosuppression was more severe than the early one. Treatment by the thymic extract thymostimulin (TP-1R) caused a complete recovery of antibody response, with overshoot, during early phase, but only partial recovery during late phase. It is suggested that the known CCNU induced damage to stem cells, manifested at late phase, reduces the responding pool for the restorative effect of thymostimulin.

Animals↗