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From a group of ten patients with hypervascular, high-grade, supratentorial astrocytomas, five were treated with pre-operative radiotherapy alone, and five with radiotherapy in combination with cytostatic drugs. The aim was to investigate the timing of intracranial operations in the multimodality therapy of brain tumors. The tumor size was diminished only in one case, but tumor vascularization was reduced in half of the cases by the pre-operative treatment. Survival was not improved. Surgical treatment still should be the first of the therapeutic measures. Pre-operative radiotherapy may be of value to reduce tumor vascularization in hypervascular, centrally localized tumors.
From September, 1972 to December, 1976, 102 consecutive patients operated on for glioblastoma multiforme were randomized, after total or subtotal tumor resection, to receive irradiation alone, irradiation plus BCNU or irradiation plus CCNU. BCNU and CCNU adjuvant chemotherapy was repeated every 6--8 weeks as long as the patients remained in complete remission. Patients were comparable for median age, type of surgery, and histological grade III and IV. Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups. The percent of optimal dose administered was 96% for BCNU and 93% for CCNU. In the group treated with radiotherapy alone (32 cases) the median survival was 10.5 months, while in the groups treated with BCNU (34 cases) and CCNU (36 cases) the median survival was 12 and 16 months, respectively. Both relapse-free (P = 0.05) and total survival (P = 0.03) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery. Present results show that in resectable glioblastoma multiforme, a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy. The cure rate was not improved.
The combinations of amphotericin B (AmB) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-cyclohexyl isocyanate, the carbamoylating decomposition product of CCNU, were more potent in lysing HL-60 cells than the combinations of AmB with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) or 2-chloroethyl isocyanate, the carbamoylating decomposition product of BCNU. The noncarbamoylating nitrosoureas 1-(2-chlorethyl)-3-(2,6-dioxo-3-piperydyl)-1-nitrosourea and 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose did not alter AmB effects on HL-60 cells. These results indicate that the potentiating action of CCNU and BCNU on the lytic effects of AmB is associated with the carbamoylating activity of these nitrosoureas. It is likely that the greater carbamoylating activity of CCNU, compared to BCNU, is responsible for the differences in potency of the two AmB-drug combinations.
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An update in cancer chemotherapy that deals with the various therapies of lung cancer is described. At present, the stage of the disease and cell type are the major factors that determine the treatment. Important differences in the biological behavior and response to treatment exist between small cell and non-small cell cancers. The small cell type is sensitive to many chemotherapeutic agents. Differences in response to chemotherapy and survival have been less among the non-small cell types.The treatment of non-small cell carcinomas including squamous cell, large cell, and adenocarcinoma are reviewed in Part I of this paper. Small cell lung cancer will be described in Part II, which will be published in a future issue of the journal.
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From 1957 to 1976, 143 patients with small cell lung cancer (SCLC) were treated with surgical resection followed by chemotherapy. The 5 year survival rates were 38.7%, 8.7% and 3.5% in stages I, II and III. The prognostic factors were clinical stage and chemotherapy. 4 stage I and 1 stage II patients without chemotherapy have survived for more than 5 years. It seems to suggest that SCLC in stage I be indicated for surgery. 4 stage III have survived for more than 5 years, all of whom had received postoperative chemotherapy for more than 4 courses. From 1980 to 1982, 96 patients with SCLC were treated, 37 of whom by chemotherapy combined with surgery. 11/37 patients were alive for more than 2 years, 7 for more than 3 years and 4 for more than 4 years. In the preoperative chemotherapy followed by selective resection plus postoperative chemotherapy group (13 patients), the mean survival time was 22.7 months, but in the postoperative chemotherapy group (24 patients), it was 11.0 months. It indicates that full-dose chemotherapy before and after operation may be superior to the postoperative chemotherapy alone.
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Despite the prevalent scepticism regarding its value, chemotherapy for metastatic renal cell cancer was used in 45 patients, of whom 44 were nephrectomized, aged between 34 and 75 yr with a mean age of 57.3 yr. In 32 patients chemotherapy was used as palliative treatment because of the presence of their often multiple metastases or in 13 patients following surgical removal of metastases and/or histologically high-grade malignancy, as adjuvant treatment. Our treatment schedule consisted on day 1 of vinblastine 5 mg/m2 to a maximum of 10 mg provided intravenously in 1 or 2 to 3 week intervals X 6 and CCNU 130 mg/m2 orally each 6th week. This treatment schedule was supported by an intensive antiemetic regimen. Gastrointestinal side effects were well tolerated while 30% hematological depression necessitated extension of treatment intervals. The mean number of cycles was 2.5-3.7, respectively, with a maximum of 6. Palliative treatment resulted in 19% complete plus partial remission, 62% stabilization, and 19% progression, while adjuvant therapy proved to be superior with 10 of 13 patients in remission at 3-21 months, and 1 of 3 patients with metastatic recurrence in further remission for 20 months; two of three patients died. Palliative chemotherapy with CCNU-vinblastine acted successfully by blocking cancer progression, while adjuvant treatment together with surgical extirpation of metastases may have prolonged tumor-free remission.
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Fifty-one patients with advanced malignant melanoma (M. D. Anderson Stage IV) were treated with a four-drug regimen known as the BOLD protocol. In brief, the 5-day treatment consisted of bleomycin, 7.5 U subcutaneously (SC) on the first course and 15 U on days 1 and 4; vincristine, 1 mg/m2 intravenously (IV) on days 1 and 5; CCNU, 80 mg/m2 orally on day 1; and DTIC, 200 mg/m2 IV on days 1 through 5. The entire cycle was repeated every 4 to 6 weeks. Sixteen patients had been previously treated for localized disease with surgery and bacillus Calmette-Guerin (BCG) immunotherapy before relapsing with advanced disease. The BCG therapy was continued in these patients during the between-cycle periods. There were only two short-lived partial responses (4%). The median survival time for all patients was 17.0 weeks and for those who completed at least two chemotherapy cycles (44 patients) was 17.3 weeks. Four candidate prognostic factors were analyzed with respect to the overall survival of all patients: age, sex, site of metastatic spread, and use of concurrent BCG therapy. None played a significant explanatory role either in univariate or multivariate analyses. These unfavorable results preclude the recommendation of this multiagent therapy as a substitute for single-drug (DTIC) regimens aimed at the palliation of advanced, disseminated malignant melanoma.
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