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At least 253 records · Page 14Linked to original sources
PubMed1991

Chemotherapy of brain metastases from lung carcinoma: a controlled randomized study.

A controlled randomized study was carried out to evaluate the effects of chemotherapy in patients with brain metastases from lung carcinoma. One hundred patients were randomly divided into three groups at the time of diagnosis or after surgery for metastases. Group A received radiotherapy alone; Group B received radiotherapy and chloroethylnitrosoureas (methyl-CCNU, 100-120 mg/m2, or ACNU 80-100 mg/m2, every 6-8 weeks), and Group C received radiotherapy and a combination of chloroethylnitrosoureas and tegafur (300 mg/m2, daily). Of the 100 patients, 88 could be evaluated. The reduction rates of the tumors of the patients in whom tumor was not surgically removed or not totally removed were compared. Complete resolution of the tumor was noted in 29, 69, and 63% of the patients in Groups A, B, and C, respectively. Tumor regression of greater than or equal to 50% was seen in 36, 69, and 74% of the patients in Groups A, B, and C, respectively. The difference in the response rates of Groups A and C was statistically significant (P less than 0.05). Median survival after the start of treatment for brain metastasis was 27, 30.5, and 29 weeks in Groups A, B and C, respectively. There was 1 long-term survivor (more than 5 years) in Group A, 3 in Group B, and 1 in Group C. The main cause of death was deterioration attributable to the primary lesion or systemic metastasis, and no statistical difference was noted in survival time among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1976

Alterations in 3H-thymidine incorporation into DNA induced by methyl CCNU (1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea) in normal and tumorous tissues in vivo.

Methyl CCNU produces a suppression of tritiated thymidine (3H-TdR) incorporation into DNA in vivo in normal bone marrow and gastrointestinal tissues which is different in magnitude and duration from that seen in L1210 ascites tumor in the same animals. This suppression and recovery pattern is not seen in animals bearing L1210 ascites tumor resistant to MeCCNU. Where a different pattern of recovery is seen between normal host target tissues and tumor, the pattern can be exploited to increase the cure rate of animals bearing advanced L1210 ascites tumor with properly spaced second doses of MeCCNU. Additional information on the potential toxicity of second doses of MeCCNU can be predicted from knowledge of the time of recovery of DNA synthesis in the normal host target tissues.

Animals↗
PubMed1979

A simple method for producing different growth fractions in vitro for use in anti-cancer drug studies.

A simple technique has been used experimentally to produce in vitro Chinese hamster ovary cells with growth fractions ranging from 0 to 100%. Known numbers of exponentially growing and plateau-phase tissue culture cells were mixed in various proportions to yield the desired final growth fraction. Cells attach to the culture flask surface within 1 hr of mixing. Treatment at that time with the nitrosourea compounds, CCNU and MeCCNU, resulted in differential drug survival sensitivities that were dependent upon the growth fraction of the population treated.

Animals↗
PubMed1984

Prospective randomised trial of early cytotoxic therapy for recurrent colorectal carcinoma detected by serum CEA.

Of 663 patients treated with radical surgery for colorectal cancer, 52 showed a progressive rise in serum carcinoembryonic antigen (CEA) with no other evidence of recurrent disease and were randomised in a prospective study of chemotherapy. Twenty six patients in the treatment group received 5FU and methyl CCNU from the time of randomisation and the remaining 26 controls were given further therapy only if there were clinical indications. All patients were followed for five years or until their death and all but one (control) developed clinical evidence of recurrence. Overall there was no significant difference between the two groups with respect to disease free interval and survival. Whereas the rise in CEA in controls was generally progressive, marked inflections on the CEA curves were seen in the majority of patients receiving early treatment. Eight of 26 treated patients showed a fall in CEA of greater than 20% two months after starting therapy. These patients had a median disease free interval of 90 weeks and a median survival of 107 weeks, these figures being longer than those of treated patients who did not show a fall in CEA and control patients. The serum CEA therefore appeared to give important prognostic information in patients receiving cytotoxic treatment. Early therapy was generally well tolerated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1978

[Immuno-chemotherapy in patients with disseminated metastasizing stage III melanoma. Randomized study with methyl-CCNU versus C. parvum plus methyl-CCNU].

34 patients with disseminated malignant melanoma (stage III) were randomized to the following therapy groups: Chemotherapy (MeCCNU, NSC 99441; 200 mg/m2, given orally every 8 weeks), or immuno-chemotherapy (1 mg Corynebacterium parvum i.v., on days 1-4 + MeCCNU 200 mg/m2 on day 8, repeated every 7 weeks). Total therapy response rate was 33%; total and partial remissions were achieved in 26% of the patients receiving chemotherapy, and in 40% under immuno-chemotherapy. Interim life table analysis shows that in the group receiving C. parvum + MeCCNU 50% of the patients survived more than 12 months, whereas in the group with MeCCNU survival of 50% was 6 months. Pretreatment with C. parvum did not only potentiate the therapeutic effect, but also reduce the myelosuppression of MeCCNU.

Bacterial Vaccines↗
PubMed1977

Methyl-CCNU in malignant melanoma--a divided dose schedule of administration.

Methyl-CCNU (NSC-95441) was administered to patients with malignant melanoma in a split dose schedule. Nausea and vomiting were eliminated as clinical problems during therapy. Response rate to the drug seemed somewhat lower than the average of three previously reported disease-oriented phase II trials, though the difference was not significant statistically. The time course of myelosuppression seemed comparable to that seen with a single dose schedule of administration.

Bone Marrow↗
PubMed1980

Chemotherapy of advanced, hormonally resistant prostatic carcinoma.

9 advanced prostate cancer patients were given a dose of 1-(2-chlorethyl-3[4-methyl cyclohexyl]-1-nitrosourea) (MeCCNU) 175 mg/m2 orally every 6 weeks. All of them had previously failed on hormonal therapy. 8 patients have progressed during the chemotherapy and only 1 was considered to be stable during a period of 18 weeks. Hematologic toxicity was seen in 3 patients. 21 patients with advanced prostatic carcinoma who failed hormonal therapy were treated with a combination of estracyt (600 mg/m2/day) plus MeCCNU (175 mg/m2/6 weeks) in oral doses. 1 patient had stable disease for about 30 weeks and another one had a subjective response for 12 weeks. 11 patients had hematologic toxicity and 5 of them required dose modification. 10 patients with stage D carcinoma of the prostate were given oral estracyt at a dose of 600 mg/m2/day plus cis-diamminedichloroplatinum (DDP) at an intravenous dose of 60 mg/m2 twice a week repeated every 3 weeks plus methotrexate (MTX) at an i.v. dose of 100 mg/m2 twice a week, repeated every 3 weeks. All of the patients had failed on prior therapy. 9 patients are evaluable, 4 patients had an objective response and 2 others had a subjective response. 2 patients had hematologic toxicity (life threatening) and 2 others had a decrease in creatinine clearance to 60 mg/min and required dose modification. The combination of estracyt + DDP + MTX or a modification seems to be promising.

Antineoplastic Agents↗
PubMed1980

Combination chemotherapy in advanced gastrointestinal malignancy.

This study compares two combinations of drugs with proven activity in gastrointestinal malignancy. The drugs utilized are 5-fluorouracil (5FU), mitomycin C (Mito C), and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU). All 57 patients received 5FU 25 mg/kg as a 24-hour infusion for 5 days every 4 weeks. One group received Mito C 20 mg/m2 IV bolus every 8 weeks. The second group received MeCCNU 150 mg/m2 orally every 8 weeks. These combinations are tolerable, and the toxicities are acceptable. The response to 5FU/Mito C is more efficacious at 47% than 5FU/MeCCNU at 25% in the treatment of evaluable patients with colorectal malignancy.

Adenocarcinoma↗
PubMed1984

The problem of permanent bone marrow damage after cytotoxic drug treatment.

The majority of cytotoxic drugs exert a dose-dependent injury to the hemopoietic bone marrow. In experimental systems, two different types of damage to the hemopoietic stem cell compartments have been demonstrated to occur following cytotoxic drug exposure. First, a reversible reduction of the size of these stem cell compartments; recovery of compartment size results from a transiently increased proliferative activity of those stem cells surviving the cytotoxic drug exposure. Second, irreversibly decreased proliferative potential of pluripotent stem cells has been observed after some cytotoxic agents. Experimental evidence indicates that such permanent stem cell damage may lead to the failure of the hemopoietic bone marrow to produce sufficient numbers of blood cells. There are indications that a similar permanent damage to the hemopoietic system may occur in man following repeated exposure to at least some cytotoxic agents.

Animals↗
PubMed1986

Cure rates and tumor resistance in cured mice after nitrosourea treatment of EMT6 ascites tumors.

Single-dose BCNU or chlorozotocin (CLZ) treatment of EMT6 mammary carcinoma tumors of the BALB/c mouse has only a transient effect on tumor growth, after which tumors follow control growth patterns. To test the hypothesis that drug access to tumor cells might be a factor in cell killing, we adapted the EMT6/KY tumor to ascites form. Injection of 10(5) EMT6/KY cells i.p. kills BALB/c mice with a mean survival time of 13.0 +/- 1.0 days. We have surveyed several nitrosoureas for their effects on the EMT6/KY ascites tumor after intraperitoneal injection of the drugs. Cure rates and percent increase in life span were used as endpoints. Also, we tested for induced host tumor resistance (TR) in cured mice, by challenging survivors with live EMT6 cells. Highest cure rates were obtained for treatment on days 2, 3, or 4 after inocula of 10(5) cells: CLZ (10 mg/kg), 83.3%; cis-acid (20 mg/kg), 75%, and CCNU (30 mg/kg), 70%. Other nitrosoureas, i.e. BCNU, PCNU, GANU, STZN, FCNU, ACNU, MeCCNU, NSC-88104 produced lower cure rates. Cured mice surviving challenges of 10(6) EMT6 cells were considered TR. TR mice did not correlate with cure rates for the 3 nitrosoureas giving high cure rates. As percent of survivors, TR mice were (for day 3 treatment): FCNU, 100%, BCNU, 100.0% and CLZ, 50.0%. Thus, cure rates and TR seem to depend on the structure of the nitrosourea, but through different mechanisms.

Animals↗
PubMed1987

Adjuvant immunochemotherapy in colorectal cancer Dukes C.

The initial aim of the present study was to verify in a randomized trial whether the addition of Levamisole, an immunomodulator, could increase the effectiveness of postoperative chemotherapy (MeCCNU + 5-FU) in Dukes C colorectal cancer patients. After entering 29 consecutive patients, the poor results of most studies of adjuvant therapy in colorectal cancer prompted an early end to patient accrual. After 8 years, the lack of significance in survival (48.9 versus 37.3%) and disease-free survival (50 versus 38.8%) between the two treatment arms rules out any improvement associated with Levamisole administration.

Adjuvants, Immunologic↗
PubMed1979

Combination chemotherapy with 5-fluorouracil and methyl-CCNU for the treatment of advanced gastrointestinal cancer.

Sixteen patients with advanced gastrointestinal cancer (colorectal 12/16, gastric 4/16) were treated with a combination of 5-fluorouracil (5-FU) plus 1-(2-chlorethyl)-3(4-methyl-cycloexyl)-1-nitrosourea (Me-CCNU). The therapeutic program consisted of orally administered Me-CCNU (140 mg/m2) and intravenous 5-FU (9.5 mg/kg by bolus injection for 5 days). The cycles were repeated at 6-week intervals. At the beginning of the therapy, 11/16 patients were in performance status (PS) 0-1 and 5 patients in PS 2-3. Eight patients developed early progressive disease between the 1st and 2nd course of therapy. Only a minor tumor response was observed in the remaining 50% of the patients. However, the patients with stabilized disease lived longer (11.8 months) than non-responders (3.5 months).

Adult↗
PubMed1983

Methyl-CCNU, 5-fluorouracil, vincristine, and streptozocin (MOF-STREP) in metastatic colo-rectal carcinoma.

Forty patients with metastatic colorectal carcinoma who had received no prior chemotherapy were entered onto a trial of methyl-CCNU, 5-fluorouracil, vincristine, and streptozocin (MOF-STREP). Ten of 40 (25%) responded. Two patients (5%) achieved a complete response and eight patients (20%) a partial response. In addition, 10 patients previously treated with chemotherapy received the MOF-STREP regimen; 1 of 10 (10%) responded. The duration of the complete responses were 5 and 16 mo, respectively. The median duration of the partial responses was 4 mo with a range of 1-16 mo. The median survival of the 11 responders was 14 mo. Median survival of the 39 nonresponders was 5 months. Responders lived significantly longer than nonresponders (p = 0.03, log-rank). Toxicity was severe with nausea and vomiting common after streptozocin and myelosuppression requiring dose reductions in 70% of patients. We compare our findings using this regimen to those of two previously reported trials.

Adult↗
PubMed1984

An Eastern Cooperative Oncology Group evaluation of combinations of methyl-CCNU, mitomycin C, Adriamycin, and 5-fluorouracil in advanced measurable gastric cancer (EST 2277).

In a prospectively randomized trial, patients with advanced locally recurrent or metastatic gastric adenocarcinoma were randomized to receive 5-fluorouracil (5-FU) and methyl-CCNU; 5-FU, Adriamycin (Adria Laboratories, Columbus, Ohio), and methyl-CCNU; 5-FU, Adriamycin, and mitomycin C; or Adriamycin and mitomycin C alone. One hundred eighty-three previously untreated evaluable patients were randomized among the four arms. An additional 39 patients previously treated with 5-FU, were assigned to treatment directly to Adriamycin and mitomycin C. Response rates were 14%, 29%, 39%, and 29%, respectively, among previously untreated patients and 21% for Adriamycin and mitomycin C among previously treated patients. 5-Fluorouracil, Adriamycin, and mitomycin C, the arm containing the largest number of responders (18), was the combination associated with the longest median survival. A larger proportion of patients in this arm survived one year or more. In addition, the 5-FU, Adriamycin, and mitomycin C program had the lowest rate of severe or worse toxicity of any of the treatments and was effective in patients who were less than fully ambulatory and in those who had lost weight. 5-Fluorouracil, Adriamycin, and mitomycin C appear to be a likely combination to be considered in a surgical adjuvant program.

Adenocarcinoma↗
PubMed1984

Phase II study of methyl-CCNU, vincristine, 5-fluorouracil, and streptozotocin in advanced colorectal cancer. By the Gastrointestinal Tumor Study Group.

In an attempt to confirm the previously reported response rates with methyl-CCNU, vincristine, 5-fluorouracil, and streptozotocin (MOF-strep) (34%) in advanced colorectal cancer, the Gastrointestinal Tumor Study Group used the identical treatment schedule in 40 good performance status patients who had received no prior chemotherapy. Four patients (10%) achieved an objective partial tumor response and the median survival for all patients was 7.3 months. The toxicity was evidenced by moderate nausea and vomiting and myelosuppression with one treatment-related death. Based on this trial further evaluation of MOF-strep for advanced colorectal cancer cannot be recommended.

Antineoplastic Combined Chemotherapy Protocols↗