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[Combination chemotherapy of transplanted rat leukemia L 5222 with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and cyclophosphamide (CPA) as well as with methyl-CCNU and CPA (author's transl)].

The acute transplanted rat leukemia L 5222 was used to investigate the two-drug combinations 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and cyclophosphamide (CPA) as well as methyl-CCNU and CPA. A therapeutic synergism could not be demonstrated in either combination. In both combinations the monotherapy with the nitrosourea was superior to the combination as well as to the monotherapy with CPA.

Animals↗

[Interim results of the SIOP study (author's transl)].

Since 1975, the International Society of Paediatric Oncology has been carrying on a cooperative therapeutic trial, the aim of which is to find out whether adjuvant chemotherapy with vincristine and CCNU, added to standarized radiotherapy of the whole central nervous system, can improve life expectancy in medulloblastoma and high-grade ependymoma. Up to 1st July, 1977, 164 patients from 14 different countries had been entered into the trial. Up to now, results do not yet permit a statistically valid conclusion as to the superiority of one method of treatment over the other.

Adolescent↗

Effect of the thymic factor, thymostimulin (TP-1), on the survival rate of tumor-bearing mice.

The effect of treatment with the thymic factor thymostimulin (TP-1) on the survival rate of tumor-bearing mice was studied, using C57BL/6 mice inoculated with 1 x 10(5) Lewis lung carcinoma (3LL) cells. TP-1 given from inoculation day (4 mg/kg, twice weekly) caused a delay in the appearance of primary tumor [14.4 +/- 1.1 (S.E.) days in control; 18.5 +/- 1.4 days in TP-1-treated animals; p less than 0.05], without changing ultimate survival rate. When primary tumor was resected, the incidence of fatal lung metastasis increased as a function of tumor size on resection day. TP-1 given after resection (same dose schedule) significantly increased survival rate as compared to resection only, provided that resected tumor diameter was less than 1.7 mm. The combination of TP-1 and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; single i.p. injection, 50 mg/kg) was effective in either resected or nonresected primary tumor. Without resection, TP-1 with CCNU cured (more than 6 months free of tumor; untreated animals died within 30 to 44 days) 55% of the animals, as compared to 23% cured by CCNU alone (p less than 0.01). With resection animal cure rates were: resection (resected tumor diameter, 0.7 to 1.7 mm) alone, 42% cured; resection with CCNU, 47% cured; resection with TP-1, 70% cured; resection with CCNU and TP-1, 100% cured (last two groups significantly different from resection only). The results indicate a profound effect of TP-1 in prolonging life and increasing cure of tumor-bearing mice. This effect was manifested when tumor load was small and was apparently more pronounced on metastatic than on primary tumor.

Animals↗

Evaluation of vincristine, CCNU and methyl-CCNU at high level doses in an experimental murine renal adenocarcinoma model.

Balb/C mice were implanted with tumor cells from primary tumor in donor animals bearing renal cell adenocarcinoma. Survival time, tumor growth and metastatic occurrence in treated animals were not significantly improved by high dose Methyl-CCNU, CCNU or Vincristine. It was also concluded that the dose levels of Methyl-CCNU and CCNU used for this study were highly toxic causing early death in the animals. Such studies thus fail to support clinical hopes that these agents would be effective for chemotherapy regimens in human renal tumors.

Adenocarcinoma↗

[Pruritus in Hodgkin's disease responding to cimetidine].

A 34-year-old woman who had had intractable pruritus for 2 years experienced dramatic relief from the symptom under treatment with cimetidine. On investigation, stage IIIb Hodgkin's disease was diagnosed and responded well to chemotherapy with a remission lasting now for 2 years. After the beginning of chemotherapy cimetidine was discontinued and the pruritus did not recur.

Adult↗

Adjuvant chemotherapy with procarbazine, vincristine and prednisone for medulloblastomas. A preliminary report.

The survival of 20 children with medulloblastoma who received adjuvant chemotherapy with procarbazine, vincristine and prednisone after resection and craniospinal irradiation is compared with the preliminary results of the Children's Cancer Study Group (CCSG) and the international Society of Pediatric Oncology (SIOP) medulloblastoma studies. Survival with the chemotherapy used in the SPOG study ws not superior to the survival of children who received craniospinal irradiation only.

Cerebellar Neoplasms↗

Action of three nitrosoureas on human lymphocytes. Hypothesis of a specific effect on lymphocyte subpopulations.

RFCNU [(chloro-2-ethyl)-1-(ribofuranosylisopropylidene-2',3'-paranitrobenzoate-5')-3- nitrosourea], RPCNU [(chloro-2-ethyl)-1-(ribopyranosyltriacetate-2',3',4')-3-nitrosourea] and CCNU [(chloro-2-ethyl)-1-cyclohexyl-3-nitrosourea) were found cytotoxic in vitro for human blood lymphocytes from healthy donors at doses higher than 50 micrograms/ml. Blood lymphocytes from different individuals displayed different behaviors both in their sensitivity to nitrosoureas and in their proliferative response to mitogenic lectins. With pokeweed-mitogen-stimulated lymphocytes the main effect of all three drugs (10 micrograms/ml) was an increase of [3H]-thymidine uptake. This facilitation effect was found only in half of the experiments with phytohemagglutinin-stimulated lymphocytes, while the stimulation by concanavalin A was inhibited under the same conditions. The hypothesis that nitrosoureas might be selectively cytotoxic for a suppressor cell subpopulation might explain the observed increase of thymidine uptake.

Adult↗

Evaluation of beta-2'-deoxythioguanosine combined with methyl-CCNU or mitomycin in advanced colorectal cancer. A Southwest Oncology Group study.

Two hundred twenty eligible patients with metastatic colorectal carcinoma were treated with a combination of beta-2'-deoxythioguanosine (BTG), plus methyl-CCNU or mitomycin. There was no significant difference in overall response (CR/PR + stable) among fully evaluable patients between the mitomycin plus BTG arm 19/96 (19.7%) and the MeCCNU arm 26/87 (29.8%). Median survival of eligible patients was 19 weeks with mitomycin plus BTG versus 21 weeks with MeCCNU plus BTG: no difference. Median survival of responders (40 weeks) and patients with stable disease (35 weeks) was significantly better than patients with increasing disease (17 weeks): p + 0.001.

Adenocarcinoma↗

[Neurogliale cerebral tumors: test of chemotherapy treatment. Forty five cases (author's transl)].

It is impossible to tell the exact prognosis of the patients affected with neuroglial cerebral tumors which are being treated with cytostatic chemotherapy. This impossibility has made it necessary to repeat the different examinations given before and during the treatment of 45 patients. We contemplate a series of clinical, immunological, biological, hematological tests; then electro-encephalogram, brain scan and a echography reveal the variations in volume of the tumor. If some of the examinations are not conclusive, the others, specifically the electro-encephalogram, the mental state evaluation are accurate in determining the final evolution. Immunological shows modification of cellular immunity with a decrease of T cells (57% +/- 5,9) which are hyporeactive (PHA 1/10: 42% +/- 7,5). EEG pertubations and clinical evolution are in agreement in 80% of cases. The median survival of patients as far as EEG signs are concerned in the third month is 375 days if there is an electival improvement and 188 days in the opposite difference which is significant. Scan ications are not conclusive because of peri tumoral edema evolution and hift of medical structures can be shown by echography.

Adult↗

Procarbazine, vincristine, CCNU, and cyclophosphamide (POCC) in the treatment of metastatic malignant melanoma.

Twelve previously untreated patients with histologically documented, metastatic, malignant melanoma were treated with the combination of procarbazine, vincristine, CCNU, and cyclophosphamide, with an objective response rate of 33%. The median survival time was 10 months for responders versus 5 months for nonresponders. Bone marrow suppression was the major toxic effect. Further clinical trials are needed to better assess the utility of this combination in advanced melanoma.

Adult↗