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At least 127 records · Page 7Linked to original sources
PubMed1984

Chemotherapy after palliative resection of colorectal cancer. Yorkshire Gastrointestinal Tumour Group.

Patients with residual disease after palliative resection of colorectal cancer were randomly allocated to receive methyl CCNU and 5-Fluorouracil or followed conventionally. There was a short term improvement in overall survival at 2 years significant at the 5 per cent level but ultimately all patients died. Chemotherapy did not significantly delay progression or prolong survival in patients with local residual disease. Although patients with more disseminated disease had a poorer prognosis than those with more limited disease, survival at 18 months was significantly prolonged (P less than 0.02 greater than 0.01) by chemotherapy.

Adult↗
PubMed1988

Adjuvant treatments following curative resection for gastric cancer. The Italian Gastrointestinal Tumor Study Group.

The results of a prospective randomized trial of adjuvant treatment after curative resection for gastric cancer are reported. The study consisted of three arms: (1) surgery only; (2) chemotherapy (5-fluorouracil (FU) and 1-(2-chloroethyl)-3-(4-methylcyclohexil)-1-nitrosourea (Me-CCNU] after surgery; (3) chemo-immunotherapy (FU, Me-CCNU and levamisole) after surgery. Between March 1977 and June 1981, 235 patients were included in the study by 18 co-operating institutions. Thirteen per cent of patients in arm 2 and thirteen per cent in arm 3 suffered major toxicity, necessitating interruption of treatment. Two of these patients died of marrow aplasia. Statistical analysis of survival showed that prognosis was influenced by the well-known prognostic variables, invasion of the wall, nodal status and site of tumour. The different treatments in the three arms, however, did not show any impact on prognosis, even when adjustments were made for the most relevant prognostic variables. Given the lack of effect on survival and the presence of clinically important toxicity, FU and Me-CCNU +/- levamisole cannot be recommended as adjuvant therapy for resected gastric cancer.

Adult↗
PubMed1975

An analysis of a multiple-drug program in the treatment of patients with advanced breast cancer utilizing 5-fluorouracil, cyclophosphamide, and prednisone with or without vincristine.

Ninety patients with advanced breast cancer received a polychemotherapeutic program composed of 5-fluorouracil, cyclophosphamide, and prednisone with or without vincristine as a control group in a series of four consecutive Phase II clinical trials of new drug programs. Objective regression rates were 59% without vincristine and 46% with vincristine. Projected mean length of regressions exceeds 1 year. Site of dominant disease, disease-free interval, or performance scale score (if score was 0, 1, or 2, ECOG scale) failed to influence response rates; decreasing response rates were noted as the length of time increased after menopause. No advantage existed in patients experiencing severe myelosuppression (nadir leukocyte count of less than 1,500/mm), and appreciable response rates occurred without significant myelosuppression. The addition of vincristine to the regimen failed to increase the response rates, and only increased toxicity. The program as outlined is reasonably tolerable and effective for this group of patients with advanced breast cancer.

Antineoplastic Agents↗
PubMed1976

Clinical comparison of adriamycin and a combination of methyl-CCNU and imidazole carboxamide in disseminated malignant melanoma.

The effects of adriamycin were compared to a combination program of methyl-CCNU and imidozole carboxamide (DTIC) in 44 patients with disseminated malignant melanoma. There were objective clinical responses in 6 of 21 patients with the combination of DTIC and methyl-CCNU who received this program as primary treatment and none in 23 patients receiving adriamycin as primary treatment. Secondary responses were not observed with either treatment regimen. Toxicity with the combination program included leukocyte depression (less than 3,000/cu mm) in 25% and platelet depression (less than 100,000/cu mm) in 40% compared to 52% leukocyte depression and 16% platelet depression after adriamycin. There were no responses after the combination treatment program in the absence of myelosuppression. There was nausea and vomiting in virtually all patients, which was moderately severe in one third of the patients receiving the combination and in only 10% of those receiving adriamycin. Alopecia developed in all who received adriamycin but in only 15% of the combination treatment group. The combination treatment response of 28% was of the same order as most response rates previously reported in this disease. This randomized controlled clinical trail found adriamycin without clinical benefit and not worthy of further trial in patients with disseminated malignant melanoma.

Adult↗
PubMed1991

Activity of the human carcinogen MeCCNU in the mouse bone marrow micronucleus assay.

The nitrosourea mustard MeCCNU is the most recent organic chemical to be classified as a human carcinogen by IARC. MeCCNU gave a strong positive response when tested in the mouse bone marrow micronucleus assay. Activity was evident using either ip injection or oral gavage of the test chemical. These results further support the correlation between human carcinogens and their genotoxicity.

Animals↗
PubMed1986

Effect of Fluosol-DA/O2 on tumor-cell and bone-marrow cytotoxicity of nitrosoureas in mice bearing FSA-II fibrosarcoma.

The perfluorochemical emulsion, Fluosol-DA, combined with carbogen breathing, potentiates the effects of radiation and a number of chemotherapeutic agents in several rodent tumors. The interaction of Fluosol-DA with drugs may be quite complex. In addition to increasing the oxygen supply in the tumor, Fluosol-DA may alter the pharmacokinetics of the drug and function as a drug delivery system. A series of 4 nitrosoureas of varying lipophilicity were administered as single doses intravenously (i.v.) to C3H/Be/FeJ mice bearing subcutaneous FSa-IIC fibrosarcomas. Doses of 40 mg/kg of CCNU, 15 mg/kg of BCNU, 20 mg/kg of MeCCNU and 15 mg/kg of chlorozoticin followed by 2 hr of breathing 95% oxygen produced tumor growth delays of 7.5, 4.0, 3.8 and 2.7 days, respectively. When the drug injection was followed immediately by 0.3 ml of Fluosol-DA and 2 hr of breathing 95% oxygen, the tumor growth delay produced by CCNU, BCNU, MeCCNU and chlorozoticin increased 2-fold, 10-fold, 4.5-fold and 3.5-fold, respectively. Administration of the drugs in Fluosol-DA followed by 2 hr of 95% oxygen breathing resulted in a 3.5-fold increase in tumor growth delay with CCNU, a 17-fold increase with BCNU, a 12.5-fold increase with MeCCNU and a 6-fold increase with chlorozoticin compared to drug and 95% oxygen breathing. These results are quantified in terms of cell survival by the tumor excision assay. Effects on the bone marrow from each treatment were measured using the granulocyte-monocyte colony-forming units (CFU-GM) assay. There was no correlation between the lipophilicity of the nitrosoureas tested and the tumor growth delay produced by each treatment.

Animals↗
PubMed1977

Current status of the therapy of advanced renal carcinoma.

A preclinical murine renal model system is available for evaluation of the effectiveness of therapeutic agents. Clinical review reveals that objective response rates to hormonal agents reported since 1971 have been substantially lower than those reported prior to 1971. Many chemotherapeutic agents have not been adequately evaluated clinically or with the experimental model. Vinblastine to date may be the most active single agent with a 25% objective response rate. At the present time, it is uncertain whether combination chemotherapy or hormonal chemotherapy add to response rates obtained with single agents. There is some evidence that immunotherapy may be of some adjuvant benefit and, thus may provide an additional avenue of investigation.

Adenocarcinoma↗
PubMed1983

Ineffectiveness of chemotherapy in patients with metastatic ependymoma of the cauda equina.

Six cases of intraspinal ependymoma metastasizing outside the central nervous system have been reported. This report documents a seventh case. This patient received multiple courses of combination and single-agent chemotherapy without evidence of tumor regression. All seven patients had four things in common: early onset of disease, numerous operations, massive local recurrence at the time distant metastases were noted, and a long time period from diagnosis to death.

Adolescent↗
PubMed1984

Scheduling of combination chemotherapy for a murine melanoma, with the subrenal capsular assay.

The effect of varying schedules for administration of two drugs, dimethyl triazeno imidazole carboxamide (DTIC) and methylcyclohexyl chloroethyl nitrosourea (MeCCNU), was studied using the Harding-Passey Mouse melanoma in the subrenal capsular assay. The results of the assay indicate that the responses of the tumor varied depending on the schedule of administration. The best response, with a mean decrease in dimensions of 3.0 ocular micrometer units (+/- 1.12 SD), was noted with administration of DTIC on day 1 after tumor implantation, followed by MeCCNU on day 2. These results are similar to previously reported data in CD2F1 mice bearing intraperitoneal Harding-Passey melanoma and suggest that the subrenal capsular assay may be of use in determining the best combinations and schedules of administration for treatment of tumors.

Animals↗
PubMed1986

Combined 5-fluorouracil (5-FU) and radiation therapy following resection of locally advanced gastric carcinoma.

Twenty-five patients with locally advanced but resectable adenocarcinoma of the stomach were given concomitant postoperative radiotherapy to the tumor bed and chemotherapy with 5-Fluorouracil (5-FU). Twenty-two of the patients had regional lymph node involvement and seven had residual tumor in the surgical margins. Radiotherapy was delivered to a total dose of 5,000 rads in 7 weeks with a two-week split. 5-FU was given daily the first 3 days of each treatment period and was then continued weekly for a minimum of 1 year. At a median follow-up time of 19 months, 11 patients have relapsed, two locally and nine distally, and all have died. Thirteen patients remain alive, all but one disease-free, for a median of 21 months from diagnosis. One additional patient died of unrelated causes, free of tumor. The actuarial median survival for the whole group stands at 33 months with a projected 5-year survival of 40%. Treatment has been well tolerated.

Adenocarcinoma↗
PubMed1979

Combination chemotherapy of colorectal cancer with 5-fluorouracil, methyl-1,3-cis(2-chloroethyl)-1-nitrosourea, and vincristine.

The combination of 5-fluorouracil (5-FU), methyl-1,3-cis(2-chlorethyl)-1-nitrosourea (methylCCNU), and vincristine (VCR) has been reported to produce a 43.5% response rate in metastatic colorectal cancer, although subsequent studies did not produce such good response rates. The clinical trial reported here was undertaken to assess the reported results. In 52 evaluable patients the overall response rate was 11%. No complete remissions were observed. Six patients with colon carcinoma had a partial remission lasting for a median of ten months, with a median survival of 15 months. No responses were observed in rectosigmoid cancer. The median survival for nonresponders was 7.5 months. Thirty-three percent of the patients had significant hematological toxicity (while count) less than or equal to 1,000/mm3, platelets less than or equal to 50,000/mm3); 58% of the patients experienced nausea and vomiting; and 32% experienced some degree of neurotoxicity. In our hands the combination of 5-FU, methylCCNU, and VCR produced a response rate of 11% in metastatic colorectal cancer with a considerable amount of toxicity.

Antineoplastic Agents↗
PubMed1981

Methyl-CCNU, 6-thioguanine, and 5-fluorouracil in advanced colorectal cancer.

Consecutive studies were undertaken in advanced colorectal adenocarcinoma, comparing two different schedules of the combination methyl-CCNU, 6-thioguanine, and 5-fluorouracil in 89 patients. The two schedules exhibited similar efficacies, with a combined complete and partial remission rate of 17%, a median response duration of 36+ weeks, and a median survival of 53+ weeks. Significant symptomatic benefit was seen in 52% of patients. Toxicity was predominantly hemopoietic and gastrointestinal, being acceptable overall, with only minor qualitative differences between the two protocols. These triple-drug regimens exhibit response rates and survival patterns comparable with those reported for other multidrug combinations and some single agents. It would appear that major improvements in the management of advanced-stage disease must await the availability of more efficacious agents used alone or in combination.

Adenocarcinoma↗
PubMed1990

Pulmonary fibrosis associated with low-dose adjuvant methyl-CCNU.

Pulmonary fibrosis is a serious side effect of nitrosourea therapy, occurring most frequently in patients treated with BCNU. Pulmonary fibrosis developed in a 63 year-old male patient while being treated with adjuvant methyl-CCNU for rectal carcinoma. This toxicity is rare with methyl-CCNU, having only been reported once previously. The case of methyl-CCNU-induced pulmonary fibrosis reported here occurred at a much lower total dose than the first reported case (604 mg/m2 vs. 2,733 mg/m2). Details of the case history, including radiographic and pathologic findings, are presented.

Antineoplastic Combined Chemotherapy Protocols↗